|
1
|
Morinaga D, Sakakibara-Konishi J, Kawai Y, Morinaga Y, Mizobuchi S, Okamoto Y, Yamanaka Y, Takahashi K, Kikuchi H, Sukoh N, Takashina T, Kitai H, Konno S. Efficacy of second line and subsequent treatments of small cell lung cancer with and without immune checkpoint inhibitor combination therapy. Respir Investig 2025; 63:423-430. [PMID: 40120158 DOI: 10.1016/j.resinv.2025.03.013] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/16/2024] [Revised: 02/19/2025] [Accepted: 03/18/2025] [Indexed: 03/25/2025]
Abstract
BACKGROUND Immune checkpoint inhibitors (ICIs) combined with platinum-doublet chemotherapy (ICI-chemo) have become the standard of care for extensive-stage small cell lung cancer (ES-SCLC). However, the effect of ICI-chemo on the efficacy of subsequent chemotherapy remains unknown. This study aimed to investigate the efficacy of second and subsequent treatments of SCLC with and without ICI combination therapy. METHODS We performed an analysis of patients with ES-SCLC between January 2015 and June 2023. The ICI-chemo groups were defined as patients who received ICI-chemo as first-line therapy between September 2019 and June 2023, after ICI-chemo was reimbursed in Japan. The non-ICI-chemo groups were defined as patients who received platinum-doublet therapy between January 2015 and August 2019 and were considered eligible for ICI-chemo. RESULTS In total, 224 patients were included (91 and 133 patients who received ICI-chemo and non-ICI-chemo, respectively). There were no significant differences in patient characteristics between the groups. There was no significant difference in progression-free survival (PFS) and overall survival (OS) for first-line treatment between the two groups. The median PFS and OS periods for second-line treatment were 3.9 and 3.9 months and 10.3 and 10.7 months in the ICI-chemo and non-ICI-chemo groups, respectively, without significant difference. Most patients in both groups received amrubicin as the second-line treatment. Moreover, the PFS and OS periods for third-line treatment were not significantly different between the ICI-chemo and non-ICI-chemo groups. CONCLUSIONS In ES-SCLC, there is no significant additive effect on PFS and OS of second- and subsequent line treatments following ICI-chemo at first-line treatment.
Collapse
Affiliation(s)
- Daisuke Morinaga
- Department of Respiratory Medicine, Faculty of Medicine, Hokkaido University, North 15, West 7, Kita-ku, Sapporo, 060-8638, Japan
| | - Jun Sakakibara-Konishi
- Department of Respiratory Medicine, Faculty of Medicine, Hokkaido University, North 15, West 7, Kita-ku, Sapporo, 060-8638, Japan; Medical Network and Welfare Center, Hokkaido University Hospital, North 15, West 7, Kita-ku, Sapporo, 060-8638, Japan.
| | - Yasutaka Kawai
- Department of Respiratory Medicine, Oji General Hospital, 3-4-8, Wakakusa-cho, Tomakomai, 053-0021, Japan
| | - Yumi Morinaga
- Department of Respiratory Medicine, Obihiro-Kosei General Hospital, West 15, South 10, Obihiro, 080-0024, Japan
| | - Shohei Mizobuchi
- Department of Respiratory Medicine, NHO Hokkaido Medical Center, 5-7-1-1, Nishi-ku, Sapporo, 063-0005, Japan
| | - Yoshihiro Okamoto
- Department of Respiratory Medicine, NHO Hokkaido Medical Center, 5-7-1-1, Nishi-ku, Sapporo, 063-0005, Japan
| | - Yasunari Yamanaka
- Department of Respiratory Medicine, Iwamizawa Municipal General Hospital, 9jo, West 7, Iwamizawa, 068-8555, Japan
| | - Kei Takahashi
- Department of Respiratory Medicine, Iwamizawa Municipal General Hospital, 9jo, West 7, Iwamizawa, 068-8555, Japan
| | - Hajime Kikuchi
- Department of Respiratory Medicine, Obihiro-Kosei General Hospital, West 15, South 10, Obihiro, 080-0024, Japan
| | - Noriaki Sukoh
- Department of Respiratory Medicine, NHO Hokkaido Medical Center, 5-7-1-1, Nishi-ku, Sapporo, 063-0005, Japan
| | - Taichi Takashina
- Department of Respiratory Medicine, Iwamizawa Municipal General Hospital, 9jo, West 7, Iwamizawa, 068-8555, Japan
| | - Hidenori Kitai
- Department of Respiratory Medicine, Faculty of Medicine, Hokkaido University, North 15, West 7, Kita-ku, Sapporo, 060-8638, Japan
| | - Satoshi Konno
- Department of Respiratory Medicine, Faculty of Medicine, Hokkaido University, North 15, West 7, Kita-ku, Sapporo, 060-8638, Japan
| |
Collapse
|
|
2
|
Lin QX, Song WW, Xie WX, Deng YT, Gong YN, Liu YR, Tian Y, Zhao WY, Tian L, Gu DN. Sequential treatment of anti-PD-L1 therapy prior to anti-VEGFR2 therapy contributes to more significant clinical benefits in non-small cell lung cancer. Neoplasia 2025; 59:101077. [PMID: 39561585 PMCID: PMC11617296 DOI: 10.1016/j.neo.2024.101077] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/18/2024] [Accepted: 10/21/2024] [Indexed: 11/21/2024]
Abstract
OBJECTIVE Anti-angiogenic therapy and immune checkpoint blockade therapy are currently important treatments for non-small cell lung cancer. However, the combined use of the two therapies is controversial, and few studies have investigated the effects of different time sequences of the two therapies on treatment outcomes. METHODS The tumor-bearing mouse model was established and the mice were divided into four groups, including AA-ICB sequence group, ICB-AA sequence group, synchronization group and the control group. Immunohistochemistry was used to assess tumor microvessels and PD-L1 expression. Selected immune cell populations were evaluated using flow cytometry. Meta-analysis and clinical information were used to elucidate the clinical effects of administration sequence. RESULTS We found that anti-PD-L1 treatment followed by anti-VEGFR2 therapy exerts the best inhibitory effect on tumor growth. Different sequences of anti-angiogenic therapy and immune checkpoint blockade therapy resulted in different proportions of tumor microvessels and immune cell populations in the tumor microenvironment. We further revealed that the administration of anti-PD-L1 before anti-VEGFR brought more normalized tumor blood vessels and CD8+T cell infiltration and reduced immunosuppressive cells in the tumor microenvironment. Subsequent re-transplantation experiments confirmed the long-term benefits of this treatment strategy. The meta-analysis reinforced that immunotherapy prior to anti-angiogenic therapy or combination therapy have better therapeutic effects in advanced non-small cell lung cancer. CONCLUSION Our study demonstrated that the therapeutic effect of anti-angiogenic treatment after immune checkpoint therapy was superior to that of concurrent therapy, whereas anti-angiogenic therapy followed by immunotherapy did not bring more significant clinical benefits than independent monotherapy.
Collapse
Affiliation(s)
- Qiao-Xin Lin
- Department of Medical Oncology, the First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China
| | - Wen-Wen Song
- Department of Medical Oncology, the First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China
| | - Wen-Xia Xie
- Department of Medical Oncology, the First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China
| | - Yi-Ting Deng
- Department of Medical Oncology, the First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China
| | - Yan-Na Gong
- Department of Medical Oncology, the First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China
| | - Yi-Ru Liu
- Department of Medical Oncology, the First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China
| | - Yi Tian
- Department of Central Laboratory, Shanghai Chest Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Wen-Ya Zhao
- Department of Central Laboratory, Shanghai Chest Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Ling Tian
- Department of Central Laboratory, Shanghai Chest Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
| | - Dian-Na Gu
- Department of Medical Oncology, the First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China.
| |
Collapse
|
|
3
|
Katayama Y, Yamada T, Sawada R, Kawachi H, Morimoto K, Watanabe S, Watanabe K, Takeda T, Chihara Y, Shiotsu S, Hibino M, Harada T, Nishioka N, Iwasaku M, Tokuda S, Takayama K. Prospective Observational Study of Ramucirumab Plus Docetaxel After Combined Chemoimmunotherapy in Patients With Non-Small-Cell Lung Cancer. Oncologist 2024; 29:e681-e689. [PMID: 38241181 PMCID: PMC11067798 DOI: 10.1093/oncolo/oyae001] [Citation(s) in RCA: 4] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/28/2023] [Accepted: 11/16/2023] [Indexed: 01/21/2024] Open
Abstract
BACKGROUND A history of pre-administration of immune checkpoint inhibitors has been reported to be associated with good outcomes of ramucirumab (RAM) plus docetaxel (DOC) combination therapy for advanced non-small-cell lung cancer (NSCLC). However, existing knowledge on the clinical significance of RAM and DOC following combined chemoimmunotherapy is limited. Therefore, we evaluated the efficacy and safety of RAM plus DOC therapy after combined chemoimmunotherapy and attempted to identify the predictors of its outcomes. PATIENTS AND METHODS This multicenter, prospective study investigated the efficacy and safety of RAM plus DOC after combined chemoimmunotherapy. The primary endpoint was progression-free survival (PFS). Secondary endpoints were the objective response rate (ORR), disease control rate (DCR), overall survival (OS), and incidence of adverse events. An exploratory analysis measured serum cytokine levels at the start of treatment. RESULTS Overall, 44 patients were enrolled from 10 Japanese institutions between April 2020 and June 2022. The median PFS and OS were 6.3 and 22.6 months, respectively. Furthermore, the ORR and DCR were 36.4% and 72.7%, respectively. The high vascular endothelial growth factor D (VEGF-D) group had a significantly shorter PFS and OS. A combination of high VEGF-A and low VEGF-D levels was associated with a longer PFS. CONCLUSION Our results showed that RAM plus DOC after combined chemoimmunotherapy might be an effective and relatively feasible second-line treatment for patients with advanced NSCLC in a real-world setting.
Collapse
Affiliation(s)
- Yuki Katayama
- Department of Pulmonary Medicine, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan
| | - Tadaaki Yamada
- Department of Pulmonary Medicine, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan
| | - Ryo Sawada
- Department of Pulmonary Medicine, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan
| | - Hayato Kawachi
- Department of Pulmonary Medicine, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan
| | - Kenji Morimoto
- Department of Pulmonary Medicine, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan
| | - Satoshi Watanabe
- Department of Respiratory Medicine and Infectious Diseases, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan
| | - Kageaki Watanabe
- Department of Thoracic Oncology and Respiratory Medicine, Tokyo Metropolitan Cancer and Infectious Diseases Center Komagome Hospital, Tokyo, Japan
| | - Takayuki Takeda
- Department of Respiratory Medicine, Japanese Red Cross Kyoto Daini Hospital, Kyoto, Japan
| | - Yusuke Chihara
- Department of Respiratory Medicine, Uji-Tokushukai Medical Center, Kyoto, Japan
| | - Shinsuke Shiotsu
- Department of Respiratory Medicine, Japanese Red Cross Kyoto Daiichi Hospital, Kyoto, Japan
| | - Makoto Hibino
- Department of Respiratory Medicine, Shonan Fujisawa Tokushukai Hospital, Kanagawa, Japan
| | - Taishi Harada
- Department of Medical Oncology, Fukuchiyama City Hospital, Kyoto, Japan
| | - Naoya Nishioka
- Department of Pulmonary Medicine, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan
| | - Masahiro Iwasaku
- Department of Pulmonary Medicine, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan
| | - Shinsaku Tokuda
- Department of Pulmonary Medicine, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan
| | - Koichi Takayama
- Department of Pulmonary Medicine, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan
| |
Collapse
|
|
4
|
Goldschmidt JH, Annavarapu S, Venkatasetty D, Wang Y, Santorelli ML, Burke T, Pennell NA. Outcomes for pembrolizumab stratified by pemetrexed maintenance post pembrolizumab-platinum-pemetrexed induction in metastatic non-small-cell lung cancer. Immunotherapy 2024; 16:453-464. [PMID: 38487917 DOI: 10.2217/imt-2023-0313] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/22/2023] [Accepted: 02/23/2024] [Indexed: 03/23/2024] Open
Abstract
Aim: We assessed treatment patterns and outcomes in patients with metastatic nonsquamous non-small-cell lung cancer (mNSCLC) who initiated first-line pembrolizumab-platinum-pemetrexed (induction) in US community oncology settings. Methods: Patients initiating induction were retrospectively identified. Patients continuing pembrolizumab afterward underwent chart review. Clinical outcomes were described by maintenance pemetrexed exposure after inverse probability of treatment weighting (IPTW). Results: Median induction pembrolizumab and pemetrexed durations were 5.1 and 4.2 months. Among patients continuing pembrolizumab after induction, 64% received maintenance pemetrexed. Common discontinuation reasons for induction pemetrexed were completion of planned therapy (79%) and partial response (68%) and progressive disease (38%) and toxicity (29%) for maintenance pemetrexed. After IPTW, median overall survival and real-world progression-free survival were longer in patients continuing pembrolizumab with versus without maintenance pemetrexed (20.3 vs 12.0 months and 10.3 vs 5.8 months, respectively). Conclusion: Patient characteristics and planned treatment decisions affect maintenance pemetrexed utilization in the community oncology setting.
Collapse
|
|
5
|
Duan X, Liu X, Chen R, Pu Y. Effectiveness of PD1/PD-L1 combined with anti-angiogenic drugs in patients with advanced nonsmall cell lung cancer: A systematic review and meta-analysis. JOURNAL OF RESEARCH IN MEDICAL SCIENCES : THE OFFICIAL JOURNAL OF ISFAHAN UNIVERSITY OF MEDICAL SCIENCES 2024; 29:7. [PMID: 38524742 PMCID: PMC10956568 DOI: 10.4103/jrms.jrms_166_23] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 03/11/2023] [Revised: 09/03/2023] [Accepted: 10/25/2023] [Indexed: 03/26/2024]
Abstract
Background Protein-1 (PD-1) and programmed cell death 1 ligand 1 (PD-L1) therapy have become an important treatment approach for patients with advanced nonsmall cell lung cancer (NSCLC), but primary or secondary resistance remains a challenge for some patients. PD-1/PD-L1 combined with anti-angiogenic drugs (AAs) in NSCLC patients have potential synergistic effects, and the survival benefit may vary based on a treatment order. To investigate the efficacy of PD-1/PD-L1 combined with AAs as the treatment for patients with advanced NSCLC. Materials and Methods We comprehensively searched EMBASE, PubMed, Web of Science, CNKI, VIP, and Wanfang databases from January 2017 to September 2022. The Cochrane risk bias tool evaluated the quality of included randomized clinical trials. Newcastle-Ottawa-Scale score was used to evaluate the quality of retrospective studies. Publication bias was evaluated by funnel plot, Begg's test, and Egger's test. Results Seventeen articles were finally selected, involving 5182 patients. Meta-analysis results showed that PD1/PD-L1 combined with AAs therapy significantly improved progression-free survival (PFS) (hazard ratio [HR] = 0.61, 95% confidence interval [CI]: 0.50-0.75, P < 0.00001), overall survival (OS) (HR = 0.79, 95% CI: 0.71-0.88, P < 0.00001), and objective response rate (ORR) (risk ratio = 0.88, 95% CI: 0.81-0.96, P = 0.004), with the statistically significant difference. The sensitivity analysis demonstrated the robustness of the PFS, ORR, and OS. Conclusion The combination of PD-1/PD-L1 inhibitors with AAs in treating advanced patients has exhibited notable therapeutic advantages when contrasted with monotherapy. Specifically, the administration of PD-1/PD-L1 inhibitors in conjunction with AAs, or sequential treatment involving PD-1/PD-L1 followed by AAs, has shown enhanced therapeutic efficacy in this patient population.
Collapse
Affiliation(s)
- Xueyu Duan
- Yunnan Provincial Key Laboratory of Entomological Biopharmaceutical R&D, Dali University, Dali, Yunnan, China
- College of Pharmacy, Dali University, Dali, Yunnan, China
| | - Xiaobo Liu
- Yunnan Provincial Key Laboratory of Entomological Biopharmaceutical R&D, Dali University, Dali, Yunnan, China
| | - Ruixiang Chen
- Department of Pharmacy, Yunnan Third People’s Hospital, Kunming, Yunnan, China
| | - Yanjiao Pu
- College of Pharmacy, Dali University, Dali, Yunnan, China
| |
Collapse
|
|
6
|
Nakashima K, Umeda Y, Demura Y, Sonoda T, Tada T, Yamaguchi M, Anzai M, Kadowaki M, Oi M, Honjo C, Mitsui M, Waseda Y, Ishizuka T. Efficacy of Nanoparticle Albumin-Bound Paclitaxel (nab-PTX) Monotherapy Can Be Improved after Treatment with Immune Checkpoint Inhibitor in Patients with Non-Small Cell Lung Cancer: Long-Term Follow-Up and Updated Analysis of Two Previous Prospective Clinical Studies. Oncology 2024; 102:593-603. [PMID: 38290482 PMCID: PMC11216350 DOI: 10.1159/000535994] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/08/2023] [Accepted: 12/12/2023] [Indexed: 02/01/2024]
Abstract
INTRODUCTION Recent studies have suggested enhanced therapeutic effects of subsequent chemotherapy after immune checkpoint inhibitor (ICI) treatment, highlighting the importance of subsequent treatment selection. Nanoparticle albumin-bound paclitaxel (nab-PTX) is commonly used in subsequent chemotherapies; however, its efficacy as a subsequent treatment after ICI treatment has not been reported. METHODS We retrospectively evaluated the efficacy and safety of nab-PTX using two prospective studies that we previously reported. The first study evaluated the efficacy and safety of nab-PTX as a second-line treatment after the failure of the first-line cytotoxic chemotherapy, excluding ICI (study 1; n = 32), and the other as a subsequent treatment after failure of ICI treatment, regardless of treatment line (study 2; n = 29). RESULTS The objective response rate was significantly higher in study 2 {55.2% (95% confidence interval [CI]: 28.1-79.6)} than in study 1 (28.1% [95% CI: 13.7-46.7]) (p = 0.04). Although the disease control rate was slightly higher in study 2 (86.2% [95% CI: 65.9-97.0]) than in study 1 (71.9% [95% CI: 53.3-86.3]), there was no significant difference (p = 0.2). The median progression-free survival was significantly longer in study 2 than in study 1 (3.9 months [95% CI: 2.0-5.5] in study 1 vs. 5.6 months [95% CI: 3.0-12.8] in study 2; hazard ratio [HR]: 0.46 [95% CI: 0.27-0.81], p = 0.006). The median overall survival was slightly longer in study 2 despite the greater number of patients who received nab-PTX in late treatment line, but there was no significant difference between study 1 and study 2 (10.9 months [95% CI: 5.1-16.8] in study 1 vs. 11.9 months [95% CI: 7.6-24.8] in study 2; HR: 0.77 [95% CI: 0.46-1.31], p = 0.34). Safety profiles did not differ between the patients in studies 1 and 2. CONCLUSION Nab-PTX monotherapy may be an effective subsequent treatment option after ICI treatment.
Collapse
Affiliation(s)
- Koki Nakashima
- Third Department of Internal Medicine, Faculty of Medical Sciences, University of Fukui, Fukui, Japan
- Department of Respiratory Medicine, Municipal Tsuruga Hospital, Fukui, Japan
| | - Yukihiro Umeda
- Third Department of Internal Medicine, Faculty of Medical Sciences, University of Fukui, Fukui, Japan
| | - Yoshiki Demura
- Department of Respiratory Medicine, Japanese Red Cross Fukui Hospital, Fukui, Japan
| | - Tomoaki Sonoda
- Third Department of Internal Medicine, Faculty of Medical Sciences, University of Fukui, Fukui, Japan
| | - Toshihiko Tada
- Department of Respiratory Medicine, Japanese Red Cross Fukui Hospital, Fukui, Japan
| | - Makiko Yamaguchi
- Third Department of Internal Medicine, Faculty of Medical Sciences, University of Fukui, Fukui, Japan
| | - Masaki Anzai
- Third Department of Internal Medicine, Faculty of Medical Sciences, University of Fukui, Fukui, Japan
| | - Maiko Kadowaki
- Third Department of Internal Medicine, Faculty of Medical Sciences, University of Fukui, Fukui, Japan
| | - Masahiro Oi
- Department of Respiratory Medicine, Japanese Red Cross Fukui Hospital, Fukui, Japan
| | - Chisato Honjo
- Third Department of Internal Medicine, Faculty of Medical Sciences, University of Fukui, Fukui, Japan
| | - Miho Mitsui
- Third Department of Internal Medicine, Faculty of Medical Sciences, University of Fukui, Fukui, Japan
| | - Yuko Waseda
- Third Department of Internal Medicine, Faculty of Medical Sciences, University of Fukui, Fukui, Japan
| | - Tamotsu Ishizuka
- Third Department of Internal Medicine, Faculty of Medical Sciences, University of Fukui, Fukui, Japan
| |
Collapse
|
|
7
|
Hamai K, Katsura R, Miyake S, Fujita S, Tada S, Hirakawa T, Ueno S, Tanimoto T, Ishikawa N. A Retrospective Analysis of the Efficacy of Oral Dexamethasone in Combination With Docetaxel Plus Ramucirumab Therapy for Previously Treated Lung Cancer. Cancer Control 2024; 31:10732748241274615. [PMID: 39120923 PMCID: PMC11316262 DOI: 10.1177/10732748241274615] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/25/2024] [Revised: 07/12/2024] [Accepted: 07/22/2024] [Indexed: 08/10/2024] Open
Abstract
INTRODUCTION Docetaxel plus ramucirumab (DTX + RAM) therapy is a standard treatment for previously treated lung cancer, but many adverse events have been reported. This retrospective study was conducted to examine if the side effects of DTX + RAM therapy can be minimized by the combined use of oral dexamethasone (DEX), and to assess the therapeutic effect of DTX + RAM in patients with recurrent lung cancer. METHODS Forty patients with relapsed non-small cell lung cancer who underwent DTX + RAM therapy were divided into two groups based on the concomitant use of oral DEX, and the therapeutic effects and toxicities in the two groups were compared. RESULTS The objective response rate (ORR) was significantly better in the DEX group (P = 0.0203). The median progression-free survival (PFS) was 5.20 months vs 2.87 months (P = 0.064) in the DEX and non-DEX groups, respectively. However, the median overall survival (OS) was significantly better in the DEX group (15.17 months vs 7.37 months, P = 0.0317). The frequency of fluid retention within six months of the start of treatment was 10.0% vs 42.5% in the DEX and non-DEX groups, respectively, with the fluid retention rate being significantly higher in the non-DEX group (P = 0.039).Conclusion: Concomitant use of oral DEX during DTX + RAM therapy may facilitate the long-term continuation of treatment and contribute to OS prolongation.
Collapse
Affiliation(s)
- Kosuke Hamai
- Department of Respiratory Medicine, Hiroshima Prefectural Hospital, Hiroshima, Japan
- Department of Respiratory Medicine, JA Onomichi General Hospital, Onomichi, Japan
| | - Ryo Katsura
- Department of Respiratory Medicine, Hiroshima Prefectural Hospital, Hiroshima, Japan
| | - Shinya Miyake
- Department of Respiratory Medicine, Hiroshima Prefectural Hospital, Hiroshima, Japan
- Department of Respiratory Medicine, National Hospital Organization Higashihiroshima Medical Center, Higashihiroshima, Japan
| | - Suguru Fujita
- Department of Respiratory Medicine, Hiroshima Prefectural Hospital, Hiroshima, Japan
| | - Shinpei Tada
- Department of Respiratory Medicine, Hiroshima Prefectural Hospital, Hiroshima, Japan
- Department of Internal Medicine, Mihara Medical Association Hospital, Mihara, Japan
| | - Tetsu Hirakawa
- Department of Respiratory Medicine, Hiroshima Prefectural Hospital, Hiroshima, Japan
- Department of Respiratory Medicine, Hiroshima University Hospital, Hiroshima, Japan
| | - Sayaka Ueno
- Department of Respiratory Medicine, Hiroshima Prefectural Hospital, Hiroshima, Japan
| | - Takuya Tanimoto
- Department of Respiratory Medicine, Hiroshima Prefectural Hospital, Hiroshima, Japan
| | - Nobuhisa Ishikawa
- Department of Respiratory Medicine, Hiroshima Prefectural Hospital, Hiroshima, Japan
| |
Collapse
|
|
8
|
Takahara Y, Abe R, Nagae S, Tanaka T, Ishige Y, Shionoya I, Yamamura K, Nishiki K, Nojiri M, Kato R, Shinomiya S, Oikawa T. Investigation of response of patients with non-small cell lung cancer to docetaxel (plus ramucirumab) therapy in second-line treatment. Thorac Cancer 2023; 14:3549-3555. [PMID: 37964501 PMCID: PMC10733157 DOI: 10.1111/1759-7714.15161] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/26/2023] [Revised: 10/30/2023] [Accepted: 10/31/2023] [Indexed: 11/16/2023] Open
Abstract
BACKGROUND Several options for second-line therapy are available for patients with advanced non-small cell lung cancer (NSCLC); however, the optimal therapy remains unclear. Docetaxel (DTX) monotherapy and DTX plus ramucirumab (RAM) are the recommended second-line treatment options. However, the efficacy of these treatments remains unsatisfactory. The aim of this study was to identify the clinical characteristics of patients with NSCLC who respond to DTX or DTX + RAM and factors that predict response. METHODS Patients with NSCLC treated with DTX or DTX + RAM after second-line therapy were retrospectively analyzed. Patients were compared with those who responded or did not respond to the post-treatment efficacy assessment. RESULTS Of 53 patients, 12 (22.6%) had lung cancer that responded to DTX or DTX + RAM therapy (response group). Multivariate analysis identified the absence of immune checkpoint inhibitors (ICIs) in the immediate prior therapy and a reduced dose of DTX after the second cycle as significant independent risk factors predicting nonresponse to DTX and DTX + RAM therapy in patients with NSCLC. The overall survival was significantly longer in the response group compared to the nonresponse group (p = 0.016). CONCLUSIONS Our results suggest that DTX and DTX + RAM therapies immediately after treatment with ICI-containing regimens as well as continuation of DTX without dose reduction after the second cycle may increase the response rate and prolong survival in patients with NSCLC.
Collapse
Affiliation(s)
- Yutaka Takahara
- Department of Respiratory MedicineKanazawa Medical UniversityIshikawaJapan
| | - Ryudai Abe
- Department of Respiratory MedicineKanazawa Medical UniversityIshikawaJapan
| | - Sumito Nagae
- Department of Respiratory MedicineKanazawa Medical UniversityIshikawaJapan
| | - Takuya Tanaka
- Department of Respiratory MedicineKanazawa Medical UniversityIshikawaJapan
| | - Yoko Ishige
- Department of Respiratory MedicineKanazawa Medical UniversityIshikawaJapan
| | - Ikuyo Shionoya
- Department of Respiratory MedicineKanazawa Medical UniversityIshikawaJapan
| | - Kouichi Yamamura
- Department of Respiratory MedicineKanazawa Medical UniversityIshikawaJapan
| | - Kazuaki Nishiki
- Department of Respiratory MedicineKanazawa Medical UniversityIshikawaJapan
| | - Masafumi Nojiri
- Department of Respiratory MedicineKanazawa Medical UniversityIshikawaJapan
| | - Ryo Kato
- Department of Respiratory MedicineKanazawa Medical UniversityIshikawaJapan
| | - Shohei Shinomiya
- Department of Respiratory MedicineKanazawa Medical UniversityIshikawaJapan
| | - Taku Oikawa
- Department of Respiratory MedicineKanazawa Medical UniversityIshikawaJapan
| |
Collapse
|
|
9
|
Siringo M, Baena J, Bote de Cabo H, Torres-Jiménez J, Zurera M, Zugazagoitia J, Paz-Ares L. Future Perspectives in the Second Line Therapeutic Setting for Non-Oncogene Addicted Non-Small-Cell Lung Cancer. Cancers (Basel) 2023; 15:5505. [PMID: 38067208 PMCID: PMC10705719 DOI: 10.3390/cancers15235505] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/27/2023] [Revised: 11/19/2023] [Accepted: 11/20/2023] [Indexed: 10/16/2024] Open
Abstract
Immune checkpoint inhibitors (ICIs) have revolutionized the management of non-oncogene addicted non-small-cell lung cancer (NSCLC). Blocking the anti-PD-1 axis represents the current standard of care in the first-line setting, with drugs administered either as monotherapy or in combination with chemotherapy. Despite notable successes achieved with ICIs, most of their long-term benefits are restricted to approximately 20% of patients. Consequently, the post-failure treatment landscape after failure to first-line treatment remains a complex challenge. Currently, docetaxel remains the preferred option, although its benefits remain modest as most patients do not respond or progress promptly. In recent times, novel agents and treatment combinations have emerged, offering fresh opportunities to improve patient outcomes. ICIs combined either with antiangiogenic or other novel immunotherapeutic compounds have shown promising preliminary activity. However, more mature data concerning specific combinations do not support their benefit over standard of care. In addition, antibody-drug conjugates seem to be the most promising alternative among all available compounds according to already-published phase I/II data that will be confirmed in soon-to-be-published phase III trial data. In this report, we provide a comprehensive overview of the current second-line treatment options and discuss future therapeutic perspectives.
Collapse
Affiliation(s)
- Marco Siringo
- Department of Medical Oncology, 12 de Octubre Hospital, 28041 Madrid, Spain; (M.S.); (J.B.); (H.B.d.C.); (J.T.-J.); (M.Z.)
- Department of Medical Oncology, Sapienza University of Rome, 00100 Rome, Italy
| | - Javier Baena
- Department of Medical Oncology, 12 de Octubre Hospital, 28041 Madrid, Spain; (M.S.); (J.B.); (H.B.d.C.); (J.T.-J.); (M.Z.)
- Lung Cancer Clinical Research Group, Spanish National Cancer Research Center (CNIO), 28029 Madrid, Spain
| | - Helena Bote de Cabo
- Department of Medical Oncology, 12 de Octubre Hospital, 28041 Madrid, Spain; (M.S.); (J.B.); (H.B.d.C.); (J.T.-J.); (M.Z.)
- Lung Cancer Clinical Research Group, Spanish National Cancer Research Center (CNIO), 28029 Madrid, Spain
| | - Javier Torres-Jiménez
- Department of Medical Oncology, 12 de Octubre Hospital, 28041 Madrid, Spain; (M.S.); (J.B.); (H.B.d.C.); (J.T.-J.); (M.Z.)
- Lung Cancer Clinical Research Group, Spanish National Cancer Research Center (CNIO), 28029 Madrid, Spain
| | - María Zurera
- Department of Medical Oncology, 12 de Octubre Hospital, 28041 Madrid, Spain; (M.S.); (J.B.); (H.B.d.C.); (J.T.-J.); (M.Z.)
- Lung Cancer Clinical Research Group, Spanish National Cancer Research Center (CNIO), 28029 Madrid, Spain
| | - Jon Zugazagoitia
- Department of Medical Oncology, 12 de Octubre Hospital, 28041 Madrid, Spain; (M.S.); (J.B.); (H.B.d.C.); (J.T.-J.); (M.Z.)
- Lung Cancer Clinical Research Group, Spanish National Cancer Research Center (CNIO), 28029 Madrid, Spain
- Ciberonc, 28029 Madrid, Spain
| | - Luis Paz-Ares
- Department of Medical Oncology, 12 de Octubre Hospital, 28041 Madrid, Spain; (M.S.); (J.B.); (H.B.d.C.); (J.T.-J.); (M.Z.)
- Lung Cancer Clinical Research Group, Spanish National Cancer Research Center (CNIO), 28029 Madrid, Spain
- Ciberonc, 28029 Madrid, Spain
- Medicine Department, Medicine Faculty, Complutense University, 28040 Madrid, Spain
| |
Collapse
|
|
10
|
Garon EB, Visseren-Grul C, Rizzo MT, Puri T, Chenji S, Reck M. Clinical outcomes of ramucirumab plus docetaxel in the treatment of patients with non-small cell lung cancer after immunotherapy: a systematic literature review. Front Oncol 2023; 13:1247879. [PMID: 37731641 PMCID: PMC10507469 DOI: 10.3389/fonc.2023.1247879] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/26/2023] [Accepted: 08/10/2023] [Indexed: 09/22/2023] Open
Abstract
Introduction In the REVEL trial, ramucirumab plus docetaxel demonstrated significant improvements in overall survival (OS), progression-free survival (PFS), and overall response rate (ORR) compared with placebo plus docetaxel for treatment of metastatic non-small cell lung cancer (NSCLC) that progressed during or after platinum-based chemotherapy. Since the approval of ramucirumab plus docetaxel, immune checkpoint inhibitors (ICIs), either as single agents or in combination with chemotherapy, have become the standard of care for first-line treatment of patients with advanced NSCLC. However, efficacy and safety data for ramucirumab plus docetaxel after prior ICI treatment from randomized controlled clinical studies are lacking. Methods Following Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, a systematic literature review was performed. Electronic databases and select international oncology conference proceedings were searched. Studies published between 01 January 2014 and 01 July 2022, which evaluated 2 efficacy outcomes (and included at least 1 time-to-event endpoint) or safety outcomes of ramucirumab plus docetaxel in NSCLC that progressed after prior ICI treatment, were identified. Twelve studies were included in the analysis. Two treatment groups were selected: ramucirumab plus docetaxel after prior ICI ± chemotherapy (RAM + DTX ICI pre-treated) and ramucirumab plus docetaxel after prior chemotherapy only (RAM + DTX ICI naïve). OS, PFS, ORR, disease control rate (DCR), and safety data were extracted and descriptively summarized across both treatment groups. Results The pooled weighted median PFS and median OS were 5.7 months (95% confidence interval [CI]: 3.9-6.8) and 11.2 months (95% CI: 7.5-17.5), respectively, in the RAM + DTX ICI pre-treated group and 3.8 months (95% CI: 2.3-4.1) and 13.5 months (95% CI: 8-24.0), respectively, in the RAM + DTX ICI naïve group. The ORR and DCR ranged from 20.9% to 60.0% and from 62.4% to 90.0%, respectively, in the RAM + DTX ICI pre-treated group and from 17.7% to 20.0% and from 57.1% to 75.0%, respectively, in the RAM + DTX ICI naïve group. The safety profile across studies was consistent between both treatment groups, and no new safety signals were reported. Conclusions Cumulatively, these results support the combination of ramucirumab plus docetaxel as an effective and safe subsequent therapy for the treatment of patients with metastatic NSCLC with disease progression irrespective of previous ICI treatment.
Collapse
Affiliation(s)
- Edward B. Garon
- David Geffen School of Medicine, University of California, Los Angeles/Translational Research in Oncology-United States Network, Los Angeles, CA, United States
| | - Carla Visseren-Grul
- Eli Lilly and Company, Lilly Corporate Center, Indianapolis, IN, United States
| | - Maria Teresa Rizzo
- Eli Lilly and Company, Lilly Corporate Center, Indianapolis, IN, United States
| | - Tarun Puri
- Eli Lilly and Company, Lilly Corporate Center, Indianapolis, IN, United States
| | | | - Martin Reck
- Department of Thoracic Oncology, Airway Research Center North (ARCN), Member of the German Center for Lung Research (DZL), Lung Clinic Grosshansdorf, Großhansdorf, Germany
| |
Collapse
|
|
11
|
Hirata T, Hakozaki T. Efficacy of second-line chemotherapy after immunotherapy in advanced non-small cell lung cancer. J Thorac Dis 2023; 15:3554-3556. [PMID: 37559596 PMCID: PMC10407526 DOI: 10.21037/jtd-23-858] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/27/2023] [Accepted: 06/30/2023] [Indexed: 08/11/2023]
Affiliation(s)
- Tsuyoshi Hirata
- Department of Thoracic Oncology and Respiratory Medicine, Tokyo Metropolitan Cancer and Infectious Diseases Center, Komagome Hospital, Tokyo, Japan
| | - Taiki Hakozaki
- Department of Thoracic Oncology and Respiratory Medicine, Tokyo Metropolitan Cancer and Infectious Diseases Center, Komagome Hospital, Tokyo, Japan
- Graduate School of Advanced Science and Engineering, Faculty of Science and Engineering, Waseda University, Tokyo, Japan
| |
Collapse
|
|
12
|
Agostara AG, Roazzi L, Villa F, Romano' R, Piscazzi D, Martinelli F, Ciarlo G, Oresti S, Travaglini F, Marando A, Sartore-Bianchi A, Giannetta L, Cerea G, Siena S, Pizzutilo EG, Signorelli D. What to do after immune-checkpoint inhibitors failure in advanced non-small cell lung cancer: an expert opinion and review. Expert Rev Respir Med 2023; 17:787-803. [PMID: 37817448 DOI: 10.1080/17476348.2023.2268509] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/23/2023] [Accepted: 10/05/2023] [Indexed: 10/12/2023]
Abstract
INTRODUCTION Immune-checkpoint inhibitors (IO) have significantly improved outcomes of patients with non-oncogene-addicted non-small cell lung cancer (NSCLC), becoming the first-line agents for advanced disease. However, resistance remains a significant clinical challenge, limiting their effectiveness. AREAS COVERED Hereby, we addressed standard and innovative therapeutic approaches for NSCLC patients experiencing progression after IO treatment, discussing the emerging resistance mechanisms and the ongoing efforts to overcome them. In order to provide a complete overview of the matter, we performed a comprehensive literature search across prominent databases, including PubMed, EMBASE (Excerpta Medica dataBASE), and the Cochrane Library, and a research of the main ongoing studies on clinicaltrials.gov. EXPERT OPINION The dynamics of progression to IO, especially in terms of time to treatment failure and burden of progressive disease, should guide the best subsequent management, together with patient clinical conditions. Long-responders to IO might benefit from continuation of IO beyond-progression, in combination with other treatments. Patients who experience early progression should be treated with salvage CT in case of preserved clinical conditions. Finally, patients who respond to IO for a considerable timeframe and who later present oligo-progression could be treated with a multimodal approach in order to maximize the benefit of immunotherapy.
Collapse
Affiliation(s)
- Alberto Giuseppe Agostara
- Niguarda Cancer Center, Grande Ospedale Metropolitano Niguarda, Milan, Italy
- Department of Oncology and Hemato-Oncology, Università degli Studi di Milano, Milan, Italy
| | - Laura Roazzi
- Niguarda Cancer Center, Grande Ospedale Metropolitano Niguarda, Milan, Italy
- Department of Oncology and Hemato-Oncology, Università degli Studi di Milano, Milan, Italy
| | - Federica Villa
- Niguarda Cancer Center, Grande Ospedale Metropolitano Niguarda, Milan, Italy
- Department of Oncology and Hemato-Oncology, Università degli Studi di Milano, Milan, Italy
| | - Rebecca Romano'
- Niguarda Cancer Center, Grande Ospedale Metropolitano Niguarda, Milan, Italy
- Department of Oncology and Hemato-Oncology, Università degli Studi di Milano, Milan, Italy
| | - Daniele Piscazzi
- Niguarda Cancer Center, Grande Ospedale Metropolitano Niguarda, Milan, Italy
- Department of Oncology and Hemato-Oncology, Università degli Studi di Milano, Milan, Italy
| | - Francesca Martinelli
- Niguarda Cancer Center, Grande Ospedale Metropolitano Niguarda, Milan, Italy
- Department of Oncology and Hemato-Oncology, Università degli Studi di Milano, Milan, Italy
| | - Gabriele Ciarlo
- Niguarda Cancer Center, Grande Ospedale Metropolitano Niguarda, Milan, Italy
- Department of Oncology and Hemato-Oncology, Università degli Studi di Milano, Milan, Italy
| | - Sara Oresti
- Niguarda Cancer Center, Grande Ospedale Metropolitano Niguarda, Milan, Italy
- Department of Oncology and Hemato-Oncology, Università degli Studi di Milano, Milan, Italy
| | | | - Alessandro Marando
- Niguarda Cancer Center, Grande Ospedale Metropolitano Niguarda, Milan, Italy
| | - Andrea Sartore-Bianchi
- Niguarda Cancer Center, Grande Ospedale Metropolitano Niguarda, Milan, Italy
- Department of Oncology and Hemato-Oncology, Università degli Studi di Milano, Milan, Italy
| | - Laura Giannetta
- Niguarda Cancer Center, Grande Ospedale Metropolitano Niguarda, Milan, Italy
| | - Giulio Cerea
- Niguarda Cancer Center, Grande Ospedale Metropolitano Niguarda, Milan, Italy
| | - Salvatore Siena
- Niguarda Cancer Center, Grande Ospedale Metropolitano Niguarda, Milan, Italy
- Department of Oncology and Hemato-Oncology, Università degli Studi di Milano, Milan, Italy
| | - Elio Gregory Pizzutilo
- Niguarda Cancer Center, Grande Ospedale Metropolitano Niguarda, Milan, Italy
- Department of Oncology and Hemato-Oncology, Università degli Studi di Milano, Milan, Italy
| | - Diego Signorelli
- Niguarda Cancer Center, Grande Ospedale Metropolitano Niguarda, Milan, Italy
| |
Collapse
|
|
13
|
Assi HI, Zerdan MB, Hodroj M, Khoury M, Naji NS, Amhaz G, Zeidane RA, El Karak F. Value of chemotherapy post immunotherapy in stage IV non-small cell lung cancer (NSCLC). Oncotarget 2023; 14:517-525. [PMID: 37235814 DOI: 10.18632/oncotarget.28444] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 05/28/2023] Open
Abstract
BACKGROUND Lung cancer is the number one cause of mortality among all types of cancer worldwide. Its treatment landscape has shifted from the classic chemotherapy alone to newer regimens based on the discovery of new immunotherapy and targeted therapy drugs. However, chemotherapy is still an option for treatment of advanced non-small cell lung cancer (NSCLC) after progression on immunotherapy alone or in combination with first-line chemotherapy. METHODS This is a retrospective study based on chart review of patients diagnosed with advanced NSCLC cases who received Docetaxel as second or third line after being treated by immunotherapy and/or chemotherapy in previous lines. The data was collected from the medical records of physicians' clinics in three different hospital centers in Lebanon over the period of 5 years from July 2015 until December 2020. February 2021 was data analysis cut off time. The main aim was to assess the role of Docetaxel post-chemoimmunotherapy for patients with diagnosed NSCLC. RESULTS A total of 21 patients were included in this study. The majority of our patients were males (81%). As for histologic type, most patients had non-squamous lung cancer (67%) as compared to 33% who had squamous lung cancer. Overall, our study reported a 24% response rate to Docetaxel including stable disease and partial response and a median progression free survival (PFS) of 3 months. The mean time interval elapsed from diagnosis to the initiation of Docetaxel was 11.5 months. CONCLUSION New therapeutic options should be validated for the treatment of NSCLC in the second and subsequent lines of therapy considering the poor prognosis of this disease. The chemotherapy in second and third line may keep an important role in the treatment after progression on newer agents, but it needs more evidence in prospective studies including a larger number of patients.
Collapse
Affiliation(s)
- Hazem I Assi
- Department of Internal Medicine, Division of Hematology and Oncology, Naef K. Basile Cancer Institute, American University of Beirut Medical Center, Beirut, Lebanon
| | - Maroun Bou Zerdan
- Department of Internal Medicine, Division of Hematology and Oncology, Naef K. Basile Cancer Institute, American University of Beirut Medical Center, Beirut, Lebanon
| | - Mohammad Hodroj
- Department of Internal Medicine, Division of Hematology and Oncology, Naef K. Basile Cancer Institute, American University of Beirut Medical Center, Beirut, Lebanon
| | - Makram Khoury
- Department of Internal Medicine, Division of Hematology and Oncology, Hotel Dieu de France University Hospital, Beirut, Lebanon
| | - Nour Sabiha Naji
- Department of Internal Medicine, Division of Hematology and Oncology, Naef K. Basile Cancer Institute, American University of Beirut Medical Center, Beirut, Lebanon
| | - Ghid Amhaz
- Department of Internal Medicine, Division of Hematology and Oncology, Naef K. Basile Cancer Institute, American University of Beirut Medical Center, Beirut, Lebanon
| | - Reine Abou Zeidane
- Department of Internal Medicine, Division of Hematology and Oncology, Naef K. Basile Cancer Institute, American University of Beirut Medical Center, Beirut, Lebanon
| | - Fadi El Karak
- Department of Internal Medicine, Division of Hematology and Oncology, Hotel Dieu de France University Hospital, Beirut, Lebanon
| |
Collapse
|
|
14
|
Sonoda T, Umeda Y, Demura Y, Tada T, Nakashima K, Anzai M, Yamaguchi M, Shimada A, Ohi M, Honjo C, Waseda Y, Akai M, Ishizuka T. Efficacy and safety of nanoparticle albumin-bound paclitaxel monotherapy after immune checkpoint inhibitor administration for advanced non-small cell lung cancer: A multicenter Phase 2 clinical trial. Cancer Med 2023. [PMID: 37081729 DOI: 10.1002/cam4.5978] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/31/2023] [Revised: 03/15/2023] [Accepted: 04/08/2023] [Indexed: 04/22/2023] Open
Abstract
BACKGROUND Whether immunotherapy improves the efficacy or worsens adverse events of subsequent chemotherapy remains unclear. We performed a Phase 2 study to evaluate the efficacy and safety of nanoparticle albumin-bound paclitaxel (nab-paclitaxel) as a treatment for advanced non-small cell lung cancer (NSCLC) after treatment with programmed cell death 1 or programmed death ligand 1 [PD-(L)1] inhibitor failure. METHODS Nab-paclitaxel (100 mg/m2 ) was administered on Days 1, 8, and 15 of a 28-day cycle to patients with advanced NSCLC within 12 weeks after the failure of PD-(L)1 inhibitor treatment. The primary endpoint was objective response rate (ORR) in all patients; the secondary endpoints were disease control rate (DCR), progression-free survival (PFS), overall survival (OS), and safety. RESULTS Thirty cases were registered, and 29 cases were included in the analysis. The ORR was 55.2% (95% confidence interval [CI]: 28.1%-79.6%) and the DCR was 86.2% (95% CI: 65.9%-97.0%). The median PFS was 5.6 months (95% CI: 4.4-6.7 months), and PFS rates at 1- and 2-year timepoints were 34.5% and 13.3%, respectively. The median OS was 11.9 months (95% CI: 0.8-23.0 months). Good performance status and responder of previous PD-(L)1 inhibitor therapy were independent predictors of PFS. Grade 3 or higher toxicities included leukopenia (27.6%), neutropenia (31.0%), peripheral sensory neuropathy (6.9%), increased alanine aminotransferase and aspartate aminotransferase levels (3.4%), and interstitial lung disease (3.4%). CONCLUSIONS Nab-paclitaxel therapy improved ORR after PD-(L)1 inhibitor treatment failure with a durable response of 13% and acceptable toxicities in patients with advanced NSCLC.
Collapse
Affiliation(s)
- Tomoaki Sonoda
- Third Department of Internal Medicine, Faculty of Medical Sciences, University of Fukui, Fukui, Japan
| | - Yukihiro Umeda
- Third Department of Internal Medicine, Faculty of Medical Sciences, University of Fukui, Fukui, Japan
| | - Yoshiki Demura
- Department of Respiratory Medicine, Japanese Red Cross Fukui Hospital, Fukui, Japan
| | - Toshihiko Tada
- Department of Respiratory Medicine, Japanese Red Cross Fukui Hospital, Fukui, Japan
| | - Koki Nakashima
- Department of Respiratory Medicine, Municipal Tsuruga Hospital, Fukui, Japan
| | - Masaki Anzai
- Third Department of Internal Medicine, Faculty of Medical Sciences, University of Fukui, Fukui, Japan
| | - Makiko Yamaguchi
- Third Department of Internal Medicine, Faculty of Medical Sciences, University of Fukui, Fukui, Japan
| | - Akikazu Shimada
- Third Department of Internal Medicine, Faculty of Medical Sciences, University of Fukui, Fukui, Japan
| | - Masahiro Ohi
- Department of Respiratory Medicine, Japanese Red Cross Fukui Hospital, Fukui, Japan
| | - Chisato Honjo
- Third Department of Internal Medicine, Faculty of Medical Sciences, University of Fukui, Fukui, Japan
| | - Yuko Waseda
- Third Department of Internal Medicine, Faculty of Medical Sciences, University of Fukui, Fukui, Japan
| | - Masaya Akai
- Department of Respiratory Medicine, Japanese Red Cross Fukui Hospital, Fukui, Japan
| | - Tamotsu Ishizuka
- Third Department of Internal Medicine, Faculty of Medical Sciences, University of Fukui, Fukui, Japan
| |
Collapse
|
|
15
|
Nakamura A, Yamaguchi O, Mori K, Miura K, Tamiya M, Oba T, Yanagitani N, Mizutani H, Ninomiya T, Kajiwara T, Ito K, Miyanaga A, Arai D, Kodama H, Kobayashi K, Kaira K. Multicentre real-world data of ramucirumab plus docetaxel after combined platinum-based chemotherapy with programmed death-1 blockade in advanced non-small cell lung cancer: NEJ051 (REACTIVE study). Eur J Cancer 2023; 184:62-72. [PMID: 36905770 DOI: 10.1016/j.ejca.2023.01.025] [Citation(s) in RCA: 8] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/05/2022] [Revised: 12/26/2022] [Accepted: 01/26/2023] [Indexed: 02/12/2023]
Abstract
BACKGROUND Ramucirumab plus docetaxel (RD) is a promising treatment for previously treated advanced non-small cell lung cancer (NSCLC). However, its clinical significance after platinum-based chemotherapy plus programmed death-1 (PD-1) blockade remains unclear. RESEARCH QUESTION What is the clinical significance of RD as a second-line treatment after the failure of chemo-immunotherapy in NSCLC? STUDY DESIGN AND METHODS In this multicentre retrospective study, 288 patients with advanced NSCLC who received RDas second-line therapy after platinum-based chemotherapy plus PD-1 blockade, at 62 Japanese institutions from January 2017 to August 2020, were included. Prognostic analyses were performed using the log-rank test. Prognostic factor analyses were performed using a Cox regression analysis. RESULTS A total of 288 patients were enrolled: 222 were men (77.1%), 262 were aged <75 years (91.0%), 237 (82.3%) had smoking history and 269 (93.4%) had a performance status (PS) of 0-1. One hundred ninety-nine patients (69.1%) were classified as adenocarcinoma (AC) and 89 (30.9%) as non-AC. The types of PD-1 blockade used in the first-line treatment were anti-PD-1 antibody and anti-programmed death-ligand 1 antibody in 236 (81.9%) and 52 (18.1%) patients, respectively. The objective response rate for RD was 28.8% (95% confidence interval [CI], 23.7-34.4). The disease control rate was 69.8% (95% CI, 64.1-75.0).The median progression free survival and overall survival were 4.1 months (95% CI, 3.5-4.6) and 11.6 months (95% CI, 9.9-13.9), respectively. In a multivariate analysis, non-AC and PS 2-3 were independent prognostic factors for worse progression free survival , while bone metastasis on diagnosis, PS 2-3 and non-AC were identified as independent prognostic factors for poor overall survival. INTERPRETATION RD is a feasible second-line treatment in patients with advanced NSCLC who had received combined chemo-immunotherapy with PD-1 blockade. CLINICAL TRIAL REGISTRATION NUMBER UMIN000042333.
Collapse
Affiliation(s)
- Atsushi Nakamura
- Department of Pulmonary Medicine, Sendai Kousei Hospital, Sendai, Japan
| | - Ou Yamaguchi
- Department of Respiratory Medicine, Comprehensive Cancer Center, Saitama Medical University International Medical Center, Hidaka, Japan.
| | - Keita Mori
- Clinical Research Center, Shizuoka Cancer Center, Nagaizumi, Japan
| | - Keita Miura
- Department of Respiratory Medicine, Juntendo University Graduate School of Medicine, Tokyo, Japan
| | - Motohiro Tamiya
- Department of Thoracic Oncology, Osaka International Cancer Institute, Osaka, Japan
| | - Tomohiro Oba
- Department of Respiratory Medicine, Saitama Red Cross Hospital, Saitama, Japan
| | - Noriko Yanagitani
- Department of Thoracic Medical Oncology, The Cancer Institute Hospital of Japanese Foundation for Cancer Research, Tokyo, Japan
| | - Hideaki Mizutani
- Department of Thoracic Oncology, Saitama Cancer Center, Saitama, Japan
| | - Takashi Ninomiya
- Department of Thoracic Oncology and Medicine, National Hospital Organization Shikoku Cancer Center, Matsuyama, Japan
| | - Tomosue Kajiwara
- Department of Internal Medicine, Niigata Cancer Center Hospital, Niigata, Japan
| | - Kentaro Ito
- Respiratory Center, Matsusaka Municipal Hospital, Matsusaka, Mie, Japan
| | - Akihiko Miyanaga
- Department of Pulmonary Medicine and Oncology, Graduate School of Medicine, Nippon Medical School, Tokyo, Japan
| | - Daisuke Arai
- Department of Internal Medicine, Saiseikai Utsunomiya Hospital, Utsunomiya, Japan
| | - Hiroaki Kodama
- Division of Thoracic Oncology, Shizuoka Cancer Center, Shizuoka, Japan
| | - Kunihiko Kobayashi
- Department of Respiratory Medicine, Comprehensive Cancer Center, Saitama Medical University International Medical Center, Hidaka, Japan
| | - Kyoichi Kaira
- Department of Respiratory Medicine, Comprehensive Cancer Center, Saitama Medical University International Medical Center, Hidaka, Japan
| |
Collapse
|
|
16
|
Chen X, He F, Zhang W, Fu Y, Cao Z. Emerging trends of BCG immunotherapy for bladder cancer in last decade: a bibliometric and visualization analysis. Front Oncol 2023; 13:1092969. [PMID: 37124495 PMCID: PMC10140368 DOI: 10.3389/fonc.2023.1092969] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/08/2022] [Accepted: 03/29/2023] [Indexed: 05/02/2023] Open
Abstract
Background One of the milestones in bacterial-mediated therapy for cancer, Bacillus Calmette-Guerin (BCG) has been used to treat bladder cancer (BC) for more than 30 years. BCG immunotherapy is now the standard of care for high-grade non-muscle invasive bladder cancer (NMIBC) following transurethral resection. Methods We searched the Web of Science core collection (WoSCC) database and used bibliometric methods through CiteSpace (version 5.1.R6), VOSviewer (version 1.6.18) and R-Bibliometrix (version R 4.2.1) to analyze and discuss the current status and trends of BCG therapy of BC from 2012 to 2021 in terms of co-occurrence, co-polymerization and visualization. Results A total of 2476 publications were found, with the majority coming from the United States and China. Over the last decade, overall yearly outputs have increased fivefold, from 117 papers in 2012 to 534 records in 2021. Most publications were produced by the University of Texas System. The authors, Ashish M. Kamat of the University of Texas-MD Anderson Cancer Center in the United States, and Shahrokh F. Shariat of Weill Cornell Medical College, were pioneers in this field with the most publications. The journals, Urologic Oncology Seminars and Original Investigations, Cancers and Frontiers in Oncology, have published a dramatic increase in the number of articles, and tumor and urology nephrology research directions have received the most attention from journals. Furthermore, recent research has concentrated on muscle-invasive bladder cancer (MIBC). BCG therapy mechanism, BCG dose and strains, targeted therapy and immune checkpoint inhibitors (ICIs) for BC were attractive research contents, with ICIs (PD-1, PD-L1) being the most popular study point in recent years. With more research on tumor immunology, screening for more reliable biomarkers for precision treatment, and the development of combination regimens of ICIs, targeted treatment of BC stem cells, and personalized BC therapies may be promising areas of immunotherapy research in the coming years. Conclusion The results of this bibliometric study can provide the current status and research trends of BCG therapy for BC in the last decade, and also further complements the research content of bacterial-mediated cancer therapy.
Collapse
Affiliation(s)
- Xingfeng Chen
- School of Nursing, Shanxi Medical University, Taiyuan, China
| | - Fang He
- Department of General Surgery, Shanxi Bethune Hospital, Third Hospital of Shanxi Medical University, Shanxi Academy of Medical Sciences, Tongji Shanxi Hospital, Taiyuan, China
| | - Wenjin Zhang
- Urology Department, Third Hospital of Shanxi Medical University, Shanxi Bethune Hospital, Shanxi Academy of Medical Sciences, Tongji Shanxi Hospital, Taiyuan, China
- *Correspondence: Wenjin Zhang,
| | - Yao Fu
- School of Public Health, Shanxi Medical University, Taiyuan, China
| | - Zhiqin Cao
- School of Nursing, Shanxi University of Traditional Chinese Medicine, Taiyuan, China
| |
Collapse
|
|
17
|
Meynard L, Dinart D, Delaunay B, Fléchon A, Saldana C, Lefort F, Gravis G, Thiery-Vuillemin A, Cancel M, Coquan E, Ladoire S, Maillet D, Rolland F, Boughalem E, Martin S, Laramas M, Crouzet L, Abbar B, Falkowski S, Pouessel D, Roubaud G. Chemotherapy following immune checkpoint inhibitors in patients with locally advanced or metastatic urothelial carcinoma. Eur J Cancer 2022; 175:43-53. [PMID: 36088671 DOI: 10.1016/j.ejca.2022.08.014] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/09/2022] [Revised: 08/07/2022] [Accepted: 08/11/2022] [Indexed: 12/24/2022]
Abstract
BACKGROUND Recent studies suggest improvements in response to salvage chemotherapy (CT) after immune checkpoint inhibitors (ICIs) in several types of cancer. Our objective was to assess the efficacy of chemotherapy re-challenge after ICI, compared with second-line chemotherapy without previous ICI in patients with locally advanced or metastatic urothelial carcinoma (la/mUC). METHODS In this multicentre retrospective study, we included all patients with la/mUC initiating second or third-line chemotherapy from January 2015 to June 2020. We compared patients treated with second-line chemotherapy without previous ICI (CT2) and patients treated with third-line chemotherapy after ICI (CT3). The primary end-point was objective response rate (ORR) in CT3 compared with CT2. Secondary end-points included progression-free survival (PFS) and toxicities. RESULTS Overall, 553 patients were included. ORRs were 31.0% (95% CI, 26.5 to 35.5) and 29.2% (95% CI, 21.9 to 36.6), respectively, in CT2 and CT3, with no statistically significant differences (P = 0.62). In subgroup analyses, no differences in ORR were observed by Bellmunt risk group, type of chemotherapy (platinum or taxanes), duration of response to first-platinum-based chemotherapy (< or ≥ 12 months) or FGFR-status. Median PFS was 4.6 months (95% CI, 3.9 to 5.1) and 4.9 months (95% CI, 4.1 to 5.5) in CT2 and CT3, respectively, and grade 3-4 hematologic toxicity occurred in 35.0% and 22.4% of patients. CONCLUSION This large multicentre retrospective study provides clinically relevant real-world data. Chemotherapy re-challenge after ICI in la/mUC achieves ORR and PFS comparable with those obtained in CT2 with an acceptable safety profile. These updated results offer more promising outcomes than historically reported with second-line chemotherapy data.
Collapse
Affiliation(s)
- Lucie Meynard
- Department of Medical Oncology, Institut Bergonié, Bordeaux, France.
| | - Derek Dinart
- University Bordeaux, Inserm, Bordeaux Population Health Research Center, Epicene Team, UMR 1219, F-33000 Bordeaux, France; Inserm CIC1401, Clinical and Epidemiological Research Unit, Institut Bergonié, Comprehensive Cancer Center, F-33000 Bordeaux, France
| | - Blandine Delaunay
- Department of Medical Oncology, Institut Claudius Régaud, IUCT Oncopole, Toulouse, France
| | - Aude Fléchon
- Department of Medical Oncology, Centre Léon Bérard, Lyon, France
| | - Carolina Saldana
- AP-HP, Hopital Henri Mondor, Service d'Oncologie, Univ Paris Est Creteil, TRePCa, F-94010 Creteil, France
| | - Félix Lefort
- Department of Medical Oncology, University Hospital, Bordeaux, France
| | - Gwenaëlle Gravis
- Department of Medical Oncology, Institut Paoli Calmettes, Marseille, France
| | | | - Mathilde Cancel
- Department of Medical Oncology, University Hospital, Tours, France
| | - Elodie Coquan
- Department of Medical Oncology, Centre François Baclesse, Caen, France
| | - Sylvain Ladoire
- Department of Medical Oncology, Centre Georges François Leclerc, Dijon, France
| | - Denis Maillet
- Department of Medical Oncology, Institut de Cancérologie des Hospices Civils de Lyon (IC-HCL), Lyon, France
| | - Frédéric Rolland
- Department of Medical Oncology, Institut de Cancérologie de l'Ouest, Nantes, France
| | - Elouen Boughalem
- Department of Medical Oncology, Institut de Cancérologie de l'Ouest, Angers, France
| | - Sophie Martin
- Department of Medical Oncology Institut de Cancérologie Strasbourg Europe, Strasbourg, France
| | - Mathieu Laramas
- Department of Medical Oncology, University Hospital, Grenoble, France
| | - Laurence Crouzet
- Department of Medical Oncology, Centre Eugène Marquis, Rennes, France
| | - Baptiste Abbar
- Sorbonne Université, INSERM, Institut Pierre Louis d'Epidémiologie et de Santé Publique (iPLESP), Assistance Publique-Hôpitaux de Paris (AP-HP), Pitié Salpêtrière Hospital, Department of Medical Oncology, Institute Universitaire de Cancérologie, CLIP(2) Galilée, Paris, France
| | - Sabrina Falkowski
- Department of Medical Oncology, Clinique François Chénieux, Limoges, France
| | - Damien Pouessel
- Department of Medical Oncology, Institut Claudius Régaud, IUCT Oncopole, Toulouse, France
| | - Guilhem Roubaud
- Department of Medical Oncology, Institut Bergonié, Bordeaux, France
| |
Collapse
|
|
18
|
Efficacy and Safety of Amrubicin in Small Cell Carcinoma Previously Treated with Immune Checkpoint Inhibitors and Chemotherapy. Cancers (Basel) 2022; 14:cancers14163953. [PMID: 36010946 PMCID: PMC9406319 DOI: 10.3390/cancers14163953] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/23/2022] [Revised: 08/11/2022] [Accepted: 08/13/2022] [Indexed: 11/16/2022] Open
Abstract
Simple Summary Therapeutic efficacy of chemotherapy combined with immune checkpoint inhibitors as first-line therapy has been previously demonstrated in extensive-stage small cell lung cancer. However, there are no reports of any cytotoxic drug that is effective as second-line therapy in extensive-stage small cell lung cancer patients previously treated with chemotherapy and immune checkpoint inhibitors as a first-line treatment. In the present study, we retrospectively evaluated patients with extensive-stage small cell lung cancer to clarify whether the previous treatment with chemotherapy and immune checkpoint inhibitors impacts the efficacy and safety of amrubicin as a second-line treatment. This study shows that the efficacy and safety of amrubicin in extensive-stage small cell lung cancer remains unchanged irrespective of previous treatment with chemotherapy and immune checkpoint inhibitors. Abstract Adding an immune checkpoint inhibitor to chemotherapy to treat extensive-stage small cell lung cancer is effective. However, there are no reports of an effective second-line treatment in patients previously treated with chemotherapy and immune checkpoint inhibitors as a first-line treatment. Here, we assessed the efficacy and safety of amrubicin as a second-line treatment for extensive-stage small cell lung cancer after chemotherapy and immune checkpoint inhibitor combination therapy. The study enrolled 150 patients with extensive-stage small cell lung cancer. The efficacy and the incidence of adverse events were compared between patients previously treated with immune checkpoint inhibitors and patients without previous immune checkpoint inhibitor treatment. One hundred and twenty-three patients were eligible. There was no difference in objective response rate, time-to-treatment failure, progression-free survival, and overall survival between both groups. The incidence of adverse events was similar in both treatment groups. Pretreatment with immune checkpoint inhibitors was not associated with an increase in amrubicin-related adverse events. This study shows that the efficacy of amrubicin in extensive-stage small cell lung cancer remains unchanged irrespective of previous treatment with immune checkpoint inhibitors. Amrubicin-related adverse events did not increase in patients previously treated with immune checkpoint inhibitors.
Collapse
|
|
19
|
Satkunasivam R, Lim K, Teh BS, Guzman J, Zhang J, Farach A, Chen SH, Wallis CJ, Efstathiou E, Esnaola NF, Sonpavde GP. A phase II clinical trial of neoadjuvant sasanlimab and stereotactic body radiation therapy as an in situ vaccine for cisplatin-ineligible MIBC: the RAD VACCINE MIBC trial. Future Oncol 2022; 18:2771-2781. [PMID: 35703113 DOI: 10.2217/fon-2022-0380] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/21/2022] Open
Abstract
The utilization of neoadjuvant immune checkpoint inhibitor therapy, specifically anti-PD-1/L1 agents, prior to radical cystectomy is an emerging paradigm in muscle-invasive bladder cancer (MIBC). In situ vaccination represents a strategy to manipulate the tumor in order to augment the immune response toward improved local and distant cancer control. The authors describe the study rationale, design and objectives for RAD VACCINE MIBC, a single-arm, single-institution, phase II trial evaluating the efficacy and safety of combination neoadjuvant sasanlimab (humanized IgG monoclonal antibody that targets PD-1) with stereotactic body radiotherapy as an in situ vaccine in cisplatin-ineligible patients with MIBC. The results from this trial will establish the safety profile of this combination strategy and evaluate pathologic complete response rates.
Collapse
Affiliation(s)
- Raj Satkunasivam
- Center for Outcomes Research, Houston Methodist Hospital, Houston, TX 77030, USA
- Department of Urology, Houston Methodist Hospital, Houston, TX 77030, USA
| | - Kelvin Lim
- Department of Urology, Houston Methodist Hospital, Houston, TX 77030, USA
| | - Bin S Teh
- Department of Radiation Oncology, Houston Methodist Hospital, Houston, TX 77030, USA
| | - Jonathan Guzman
- Department of Urology, Houston Methodist Hospital, Houston, TX 77030, USA
- Department of Urology, Lenox Hill Hospital, New York, NY 10075, USA
| | - Jun Zhang
- Department of Medical Oncology, Houston Methodist Cancer Center, Houston, TX 77030, USA
| | - Andrew Farach
- Department of Radiation Oncology, Houston Methodist Hospital, Houston, TX 77030, USA
| | - Shu-Hsia Chen
- Center for Immunotherapy Research, Houston Methodist Research Institute, Houston, TX 77030, USA
| | - Christopher Jd Wallis
- Division of Urology, University of Toronto, Toronto, ON M5G 1E2, Canada
- Division of Urology, Mount Sinai Hospital, Toronto, ON M5G 1X5, Canada
| | - Eleni Efstathiou
- Department of Medical Oncology, Houston Methodist Cancer Center, Houston, TX 77030, USA
| | - Nestor F Esnaola
- Department of Surgical Oncology, Houston Methodist Hospital, Houston, TX 77030, USA
| | - Guru P Sonpavde
- Department of Genitourinary Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02215, USA
| |
Collapse
|
|
20
|
Is the Efficacy of Adding Ramucirumab to Docetaxel Related to a History of Immune Checkpoint Inhibitors in the Real-World Clinical Practice? Cancers (Basel) 2022; 14:cancers14122970. [PMID: 35740634 PMCID: PMC9221111 DOI: 10.3390/cancers14122970] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/27/2022] [Revised: 06/09/2022] [Accepted: 06/14/2022] [Indexed: 11/17/2022] Open
Abstract
Simple Summary Previous studies have shown that the use of chemotherapy in combination with immune checkpoint inhibitors as a first-line treatment in patients with non-small cell lung cancer improved overall survival and progression-free survival. However, the efficacy of cytotoxic agents as a second-line or later-line therapy in non-small cell lung cancer patients previously treated with immune checkpoint inhibitors in the real-world clinical practice is still controversial. In the present study, we retrospectively evaluated patients with non-small cell lung cancer to clarify whether the previous treatment with immune checkpoint inhibitors impacts the efficacy of docetaxel or the combined therapy of docetaxel plus ramucirumab. The results of this study using real-world data show that the addition of ramucirumab to docetaxel is superior to docetaxel monotherapy for improving time-to-treatment failure and overall survival, irrespective of previous treatment with immune checkpoint inhibitors. Abstract Reports on the efficacy of second-line treatment with cytotoxic agents after treatment with immune checkpoint inhibitors are limited. Here, we retrospectively evaluated patients in the real-world clinical practice treated with docetaxel or docetaxel plus ramucirumab. Ninety-three patients treated with docetaxel or docetaxel plus ramucirumab as a second- or later-line therapy were included. The patients were categorized into the following four treatment groups: docetaxel group (n = 50), docetaxel/ramucirumab group (n = 43) and pretreated (n = 45) and untreated (n = 48) with immune checkpoint inhibitor groups. The docetaxel/ramucirumab group showed an overall response rate of 57.1% in patients pretreated with immune checkpoint inhibitors and 20% in untreated patients. The docetaxel group showed an overall response rate of 15.4% in patients pretreated with immune checkpoint inhibitors and 5.0% in untreated patients. The median time-to-treatment failure and the median survival time were longer in the docetaxel/ramucirumab group than in the docetaxel group in both immune checkpoint inhibitor-pretreated and -untreated groups. There was no difference in time-to-treatment failure and overall survival between immune checkpoint inhibitor-pretreated and -untreated groups in each docetaxel and docetaxel/ramucirumab treatment group. In conclusion, our real-world data show that the addition of ramucirumab to docetaxel was superior to docetaxel monotherapy for improving time-to-treatment failure and overall survival, irrespective of previous treatment with immune checkpoint inhibitors.
Collapse
|
|
21
|
Kawachi H, Tamiya M, Matsumoto K, Tamiya A, Yanase T, Tanizaki S, Kumagai T. Efficacy and safety of ramucirumab and docetaxel in previously treated patients with squamous cell lung cancer: a multicenter retrospective cohort study. Invest New Drugs 2022; 40:634-642. [PMID: 35024985 DOI: 10.1007/s10637-022-01214-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/18/2021] [Accepted: 01/05/2022] [Indexed: 10/19/2022]
Abstract
OBJECTIVE Ramucirumab plus docetaxel (RAM/DOC) therapy is currently the standard for previously treated advanced non-small cell lung cancer (NSCLC), irrespective of histology. However, in the clinical trial, only the first-line platinum-based chemotherapy refractory patients were enrolled and the eligible criteria was strict to avoid hemoptysis, especially in squamous cell NSCLC (Sq). Thus, the efficacy and safety data on ramucirumab for Sq in real-world settings after immune checkpoint inhibitors monotherapy or combination therapy approved as novel first-line therapy is lacking. METHODS We retrospectively analyzed previously treated patients with advanced NSCLC who underwent RAM/DOC therapy at four institutions. Clinical data on the initiation of RAM/DOC were collected from medical records. Treatment outcomes were assessed according to the Response Evaluation Criteria in Solid Tumors version 1.1. Incidence of pulmonary hemorrhage was assessed according to the Common Terminology Criteria for Adverse Events version 5.0. RESULTS Overall, 237 patients with NSCLC were included and 38 (16%) had squamous cell carcinoma. There were no significant differences in median progression-free survival and overall survival between Sq and non-Sq patients (5.8 months vs. 4.3 months, P = 0.0937; 15.2 months vs. 13.4 months, P = 0.714, respectively). Of all patients, 13 (5%) developed pulmonary hemorrhage. According to histological analysis, there was no significant difference in pulmonary hemorrhage proportion between Sq and non-Sq cohorts (2/38 vs. 11/199, respectively, P = 0.947). CONCLUSIONS For previously treated patients with Sq, the efficacy and safety of RAM/DOC therapy were confirmed in a real-world setting and were similar to non-Sq.
Collapse
Affiliation(s)
- Hayato Kawachi
- Department of Thoracic Oncology, Osaka International Cancer Institute, Osaka, Japan.
- Department of Pulmonary Medicine, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan.
| | - Motohiro Tamiya
- Department of Thoracic Oncology, Osaka International Cancer Institute, Osaka, Japan
| | - Kinnosuke Matsumoto
- Department of Internal Medicine, National Hospital Organization Kinki-Chuo Chest Medical Center, Osaka, Japan
| | - Akihiro Tamiya
- Department of Internal Medicine, National Hospital Organization Kinki-Chuo Chest Medical Center, Osaka, Japan
| | - Takafumi Yanase
- Department of Thoracic Oncology, Osaka Habikino Medical Center, Osaka, Japan
| | - Satoshi Tanizaki
- Department of Respiratory Medicine, Osaka General Medical Center, Osaka, Japan
| | - Toru Kumagai
- Department of Thoracic Oncology, Osaka International Cancer Institute, Osaka, Japan
| |
Collapse
|
|
22
|
Zhao LP, Hu JH, Hu D, Wang HJ, Huang CG, Luo RH, Zhou ZH, Huang XY, Xie T, Lou JS. Hyperprogression, a challenge of PD-1/PD-L1 inhibitors treatments: potential mechanisms and coping strategies. Biomed Pharmacother 2022; 150:112949. [PMID: 35447545 DOI: 10.1016/j.biopha.2022.112949] [Citation(s) in RCA: 12] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/24/2022] [Revised: 04/01/2022] [Accepted: 04/08/2022] [Indexed: 11/29/2022] Open
Abstract
Immunotherapy is now a mainstay in cancer treatments. Programmed cell death 1 (PD-1)/programmed cell death ligand 1 (PD-L1) immune checkpoint inhibitor (ICI) therapies have opened up a new venue of advanced cancer immunotherapy. However, hyperprogressive disease (HPD) induced by PD-1/PD-L1 inhibitors caused a significant decrease in the overall survival (OS) of the patients, which compromise the efficacy of PD-1/PD-L1 inhibitors. Therefore, HPD has become an urgent issue to be addressed in the clinical uses of PD-1/PD-L1 inhibitors. The mechanisms of HPD remain unclear, and possible predictive factors of HPD are not well understood. In this review, we summarized the potential mechanisms of HPD and coping strategies that can effectively reduce the occurrence and development of HPD.
Collapse
Affiliation(s)
- Li-Ping Zhao
- School of Pharmacy, Hangzhou Normal University, Hangzhou, Zhejiang 311121, China; Collaborative Innovation Center of Traditional Chinese Medicines of Zhejiang Province, Hangzhou Normal University, Hangzhou, Zhejiang 311121, China; Engineering Laboratory of Development and Application of Traditional Chinese Medicines, Zhejiang 311121, China; Key Laboratory of Elemene Class Anti-Cancer Chinese Medicines, Hangzhou Normal University, Hangzhou, Zhejiang 311121, China
| | - Jun-Hu Hu
- School of Pharmacy, Hangzhou Normal University, Hangzhou, Zhejiang 311121, China; Collaborative Innovation Center of Traditional Chinese Medicines of Zhejiang Province, Hangzhou Normal University, Hangzhou, Zhejiang 311121, China; Engineering Laboratory of Development and Application of Traditional Chinese Medicines, Zhejiang 311121, China; Key Laboratory of Elemene Class Anti-Cancer Chinese Medicines, Hangzhou Normal University, Hangzhou, Zhejiang 311121, China
| | - Die Hu
- School of Pharmacy, Hangzhou Normal University, Hangzhou, Zhejiang 311121, China; Collaborative Innovation Center of Traditional Chinese Medicines of Zhejiang Province, Hangzhou Normal University, Hangzhou, Zhejiang 311121, China; Engineering Laboratory of Development and Application of Traditional Chinese Medicines, Zhejiang 311121, China; Key Laboratory of Elemene Class Anti-Cancer Chinese Medicines, Hangzhou Normal University, Hangzhou, Zhejiang 311121, China
| | - Hao-Jie Wang
- School of Pharmacy, Hangzhou Normal University, Hangzhou, Zhejiang 311121, China; Collaborative Innovation Center of Traditional Chinese Medicines of Zhejiang Province, Hangzhou Normal University, Hangzhou, Zhejiang 311121, China; Engineering Laboratory of Development and Application of Traditional Chinese Medicines, Zhejiang 311121, China; Key Laboratory of Elemene Class Anti-Cancer Chinese Medicines, Hangzhou Normal University, Hangzhou, Zhejiang 311121, China
| | - Chang-Gang Huang
- School of Pharmacy, Hangzhou Normal University, Hangzhou, Zhejiang 311121, China; Collaborative Innovation Center of Traditional Chinese Medicines of Zhejiang Province, Hangzhou Normal University, Hangzhou, Zhejiang 311121, China; Engineering Laboratory of Development and Application of Traditional Chinese Medicines, Zhejiang 311121, China; Key Laboratory of Elemene Class Anti-Cancer Chinese Medicines, Hangzhou Normal University, Hangzhou, Zhejiang 311121, China
| | - Ru-Hua Luo
- School of Pharmacy, Hangzhou Normal University, Hangzhou, Zhejiang 311121, China; Collaborative Innovation Center of Traditional Chinese Medicines of Zhejiang Province, Hangzhou Normal University, Hangzhou, Zhejiang 311121, China; Engineering Laboratory of Development and Application of Traditional Chinese Medicines, Zhejiang 311121, China; Key Laboratory of Elemene Class Anti-Cancer Chinese Medicines, Hangzhou Normal University, Hangzhou, Zhejiang 311121, China
| | - Zhao-Huang Zhou
- School of Pharmacy, Hangzhou Normal University, Hangzhou, Zhejiang 311121, China; Collaborative Innovation Center of Traditional Chinese Medicines of Zhejiang Province, Hangzhou Normal University, Hangzhou, Zhejiang 311121, China; Engineering Laboratory of Development and Application of Traditional Chinese Medicines, Zhejiang 311121, China; Key Laboratory of Elemene Class Anti-Cancer Chinese Medicines, Hangzhou Normal University, Hangzhou, Zhejiang 311121, China
| | - Xin-Yun Huang
- Department of Physiology and Biophysics, Weill Cornell Medical College of Cornell University, New York, NY 10065, USA.
| | - Tian Xie
- School of Pharmacy, Hangzhou Normal University, Hangzhou, Zhejiang 311121, China; Collaborative Innovation Center of Traditional Chinese Medicines of Zhejiang Province, Hangzhou Normal University, Hangzhou, Zhejiang 311121, China; Engineering Laboratory of Development and Application of Traditional Chinese Medicines, Zhejiang 311121, China; Key Laboratory of Elemene Class Anti-Cancer Chinese Medicines, Hangzhou Normal University, Hangzhou, Zhejiang 311121, China.
| | - Jian-Shu Lou
- School of Pharmacy, Hangzhou Normal University, Hangzhou, Zhejiang 311121, China; Collaborative Innovation Center of Traditional Chinese Medicines of Zhejiang Province, Hangzhou Normal University, Hangzhou, Zhejiang 311121, China; Engineering Laboratory of Development and Application of Traditional Chinese Medicines, Zhejiang 311121, China; Key Laboratory of Elemene Class Anti-Cancer Chinese Medicines, Hangzhou Normal University, Hangzhou, Zhejiang 311121, China.
| |
Collapse
|
|
23
|
Santos ES, Rodriguez E. Treatment Considerations for Patients with Advanced Squamous Cell Carcinoma of the Lung. Clin Lung Cancer 2022; 23:457-466. [DOI: 10.1016/j.cllc.2022.06.002] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/08/2022] [Revised: 06/10/2022] [Accepted: 06/12/2022] [Indexed: 11/27/2022]
|
|
24
|
Haag GM, Springfeld C, Grün B, Apostolidis L, Zschäbitz S, Dietrich M, Berger AK, Weber TF, Zoernig I, Schaaf M, Waberer L, Müller DW, Al-Batran SE, Halama N, Jaeger D. Pembrolizumab and maraviroc in refractory mismatch repair proficient/microsatellite-stable metastatic colorectal cancer – The PICCASSO phase I trial. Eur J Cancer 2022; 167:112-122. [DOI: 10.1016/j.ejca.2022.03.017] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/25/2022] [Accepted: 03/13/2022] [Indexed: 12/20/2022]
|
|
25
|
Kagawa Y, Sone K, Oguri T, Horiuchi M, Fukuda S, Uemura T, Takakuwa O, Maeno K, Fukumitsu K, Kanemitsu Y, Tajiri T, Ohkubo H, Takemura M, Ito Y, Niimi A. Predictive role of CYFRA 21-1 for S-1 monotherapy in non-small cell lung cancer patients. Respir Investig 2022; 60:393-399. [PMID: 35216954 DOI: 10.1016/j.resinv.2021.11.014] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/09/2021] [Revised: 11/05/2021] [Accepted: 11/23/2021] [Indexed: 06/14/2023]
Abstract
BACKGROUND S-1, an oral fluoropyrimidine derivative, is widely used for the treatment of several solid tumors. However, there are no predictive markers for its effectiveness. METHODS We retrospectively screened 108 patients with advanced non-small cell lung cancer (NSCLC) treated via S-1 monotherapy and investigated its relationship with cytokeratin 19 fragment (CYFRA 21-1) and CEA pretreatment levels. RESULTS Sixty-one patients with high CYFRA 21-1 levels had a statistically significant shorter progression-free survival (PFS) and overall survival (OS) than 46 patients with normal levels (median PFS = 42 days vs. 70 days, respectively; p = 0.0014; median OS = 197 days vs. 316 days, respectively, p = 0.0239). CONCLUSIONS Serum CYFRA 21-1 levels have predictive and prognostic roles in the management of patients with advanced NSCLC on S-1 monotherapy.
Collapse
Affiliation(s)
- Yusuke Kagawa
- Department of Respiratory Medicine, Allergy and Clinical Immunology, Nagoya, Japan
| | - Kazuki Sone
- Department of Respiratory Medicine, Allergy and Clinical Immunology, Nagoya, Japan
| | - Tetsuya Oguri
- Department of Respiratory Medicine, Allergy and Clinical Immunology, Nagoya, Japan; Department of Education and Research Center for Community Medicine, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan.
| | - Minoru Horiuchi
- Department of Respiratory Medicine, Allergy and Clinical Immunology, Nagoya, Japan
| | - Satoshi Fukuda
- Department of Respiratory Medicine, Allergy and Clinical Immunology, Nagoya, Japan
| | - Takehiro Uemura
- Department of Respiratory Medicine, Allergy and Clinical Immunology, Nagoya, Japan
| | - Osamu Takakuwa
- Department of Respiratory Medicine, Allergy and Clinical Immunology, Nagoya, Japan
| | - Ken Maeno
- Department of Respiratory Medicine, Allergy and Clinical Immunology, Nagoya, Japan
| | - Kennsuke Fukumitsu
- Department of Respiratory Medicine, Allergy and Clinical Immunology, Nagoya, Japan
| | - Yoshihiro Kanemitsu
- Department of Respiratory Medicine, Allergy and Clinical Immunology, Nagoya, Japan
| | - Tomoko Tajiri
- Department of Respiratory Medicine, Allergy and Clinical Immunology, Nagoya, Japan
| | - Hirotsugu Ohkubo
- Department of Respiratory Medicine, Allergy and Clinical Immunology, Nagoya, Japan
| | - Masaya Takemura
- Department of Respiratory Medicine, Allergy and Clinical Immunology, Nagoya, Japan; Department of Education and Research Center for Community Medicine, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan
| | - Yutaka Ito
- Department of Respiratory Medicine, Allergy and Clinical Immunology, Nagoya, Japan
| | - Akio Niimi
- Department of Respiratory Medicine, Allergy and Clinical Immunology, Nagoya, Japan
| |
Collapse
|
|
26
|
Heraudet L, Delon T, Veillon R, Vergnenègre C, Lepetit H, Daste A, Ravaud A, Zysman M, Domblides C. Effect of prior immunotherapy on the efficacy of chemotherapy in advanced non‐small cell lung cancer: A retrospective study. Thorac Cancer 2022; 13:1391-1400. [PMID: 35434866 PMCID: PMC9058314 DOI: 10.1111/1759-7714.14403] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/15/2022] [Revised: 03/10/2022] [Accepted: 03/11/2022] [Indexed: 11/29/2022] Open
Abstract
Background The effect of the sequential combination of chemotherapy and immune checkpoint inhibitors (ICIs) remains unclear. Here, we evaluated the efficacy of different chemotherapy regimens administered after ICIs in advanced non‐small cell lung cancer (NSCLC), compared to the same regimens administered without previous ICIs. Methods We retrospectively included all patients treated between 2015 and 2019 for an advanced NSCLC, receiving a salvage chemotherapy just after ICI (CAI group) comparing them to ICI naive patients (CWPI group) undergoing the same chemotherapy at Bordeaux University Hospital. The primary outcome was the time to treatment discontinuation (TTD), and secondary endpoints were overall survival (OS) and overall response rate (ORR). Results A total of 152 patients were included, with 34/23 (CAI/CWPI) receiving paclitaxel/bevacizumab (PB), 24/11 paclitaxel (P), 27/12 gemcitabine (G) and 6/15 pemetrexed (PE). Characteristics were comparable, except for CAI treated with PB (more patients with an ECOG PS ≤1 [p <0.001]). Median number of lines received was higher in CAI for all groups. There was no difference between CAI and CWPI for TTD, OS and ORR. However, PB was associated with a nonsignificant increase in OS in the CAI group (HR = 0.65; 95% CI: 0.38–1.2, p = 0.17]. Conclusion Our data showed no difference in TTD, OS and ORR regardless of chemotherapy, but a trend towards an increased OS with PB when given after an ICI, while patients received chemotherapy later in the CAI group. This suggests that a sequential combination of ICI followed by chemotherapy could be an interesting strategy in advanced NSCLC for selected patients.
Collapse
Affiliation(s)
- Luc Heraudet
- Department of Medical Oncology, Hôpital Saint‐André Bordeaux University Hospital Bordeaux France
- Faculty of Medicine University of Bordeaux Bordeaux France
| | - Tara Delon
- Faculty of Medicine University of Bordeaux Bordeaux France
- Pulmonary Department, Pôle Cardio‐thoracique, Hôpital Haut‐Lévèque Bordeaux University Hospital Bordeaux France
| | - Rémi Veillon
- Pulmonary Department, Pôle Cardio‐thoracique, Hôpital Haut‐Lévèque Bordeaux University Hospital Bordeaux France
| | - Charlotte Vergnenègre
- Pulmonary Department, Pôle Cardio‐thoracique, Hôpital Haut‐Lévèque Bordeaux University Hospital Bordeaux France
| | - Hélène Lepetit
- Unité de soutien méthodologique à la recherche clinique et épidémiologique Bordeaux University Hospital Bordeaux France
| | - Amaury Daste
- Department of Medical Oncology, Hôpital Saint‐André Bordeaux University Hospital Bordeaux France
| | - Alain Ravaud
- Department of Medical Oncology, Hôpital Saint‐André Bordeaux University Hospital Bordeaux France
- Faculty of Medicine University of Bordeaux Bordeaux France
| | - Maéva Zysman
- Faculty of Medicine University of Bordeaux Bordeaux France
- Pulmonary Department, Pôle Cardio‐thoracique, Hôpital Haut‐Lévèque Bordeaux University Hospital Bordeaux France
- Centre de Recherche Cardio‐Thoracique de Bordeaux (CRCTB), INSERM U1045 Bordeaux France
| | - Charlotte Domblides
- Department of Medical Oncology, Hôpital Saint‐André Bordeaux University Hospital Bordeaux France
- Faculty of Medicine University of Bordeaux Bordeaux France
- CNRS UMR5164, ImmunoConcEpT Site de Carreire, University of Bordeaux Bordeaux France
| |
Collapse
|
|
27
|
Guo L, Liang J, Dai W, Li J, Si Y, Ren W, Lu Y, Chen D. PD-1/L1 With or Without CTLA-4 Inhibitors Versus Chemotherapy in Advanced Non-Small Cell Lung Cancer. Cancer Control 2022; 29:10732748221107590. [PMID: 35673884 PMCID: PMC9185001 DOI: 10.1177/10732748221107590] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2022] Open
Abstract
BACKGROUND With the use of immune-checkpoint inhibitors (ICIs) in advanced or metastatic non-small cell lung cancer (NSCLC), whether ICIs or chemotherapy is more effective still remains controversial. This study was conducted to evaluate the efficacy of programmed cell death 1 (PD-1), programmed cell death ligand 1 (PD-L1), cytotoxic T-lymphocyte protein 4 (CTLA-4) alone or in their combination vs chemotherapy in patients with advanced or metastatic NSCLC. METHODS This meta-analysis was conducted from PubMed, Web of Science, Medline, Embase, and the Cochrane Library up to March 2021 to identify relevant randomized controlled trials. Primary endpoints were overall survival (OS) and progression-free survival (PFS). Secondary endpoint was adverse events (AEs). This meta-analysis's Prospero registration number is CRD42022323570. RESULTS The search process has identified 13 studies containing 7918 patients with advanced or metastatic NSCLC. The benefit of PD-1/L1 or CTLA-4 inhibitors alone or in combination compared with chemotherapy for advanced or metastatic NSCLC was elucidated in both OS [HR = .75, 95% CI (.70-.80), P < .001] and PFS [HR = .83, 95% CI (.73-.95), P < .001]. Besides, ICIs were associated with fewer AEs compared to chemotherapy. CONCLUSION PD-1/L1 or CTLA-4 inhibitors alone or in combination, with fewer AEs, was associated with significant improvements in terms of OS and PFS than chemotherapy in advanced or metastatic NSCLC.
Collapse
Affiliation(s)
- Luyong Guo
- The Emergency Department, 74784Zhuji People's Hospital, Shaoxing, China
| | - Jiali Liang
- The First Clinical Medical College, 70571Zhejiang Chinese Medical University, Hangzhou, China
| | - Wei Dai
- The Second Clinical Medical College, RinggoldID:70571Zhejiang Chinese Medical University, Hangzhou, China
| | - Jiayu Li
- The Second Clinical Medical College, RinggoldID:70571Zhejiang Chinese Medical University, Hangzhou, China
| | - Yuexiu Si
- School of Basic Medical Sciences, 70571Zhejiang Chinese Medical University, Hangzhou, China
| | - Wei Ren
- The First Clinical Medical College, 70571Zhejiang Chinese Medical University, Hangzhou, China
| | - Yan Lu
- The First Clinical Medical College, 70571Zhejiang Chinese Medical University, Hangzhou, China
| | - Danqi Chen
- Intensive Care Unit, 301513Ningbo Yinzhou No. 2 Hospital, Ningbo, China
| |
Collapse
|
|
28
|
Impact of treatment timing and sequence of immune checkpoint inhibitors and anti-angiogenic agents for advanced non-small cell lung cancer: A systematic review and meta-analysis. Lung Cancer 2021; 162:175-184. [PMID: 34823108 DOI: 10.1016/j.lungcan.2021.11.008] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/27/2021] [Revised: 10/24/2021] [Accepted: 11/14/2021] [Indexed: 01/10/2023]
Abstract
OBJECTIVE Several studies have demonstrated that anti-angiogenic agents (AAs) have the ability to regulate immune-related cells in the tumor microenvironment and may affect the clinical effect of immune checkpoint inhibitors (ICIs). Therefore, we investigated the drug interaction between ICI and AA for advanced non-small cell lung cancer (NSCLC). MATERIALS AND METHODS We systematically searched PubMed-MEDLINE, Embase-Scopus, and ISI Web of Science before August 23, 2021. ICI and AA therapy included the concomitant and sequential use of ICIs and AAs. The objective response rate (ORR), progression-free survival (PFS), and overall survival (OS) of patients who received ICI and AA therapy were evaluated and compared to those of patients who received either monotherapy. Subgroup analyses were performed to clarify the cause of heterogeneity; the timing and sequence of ICI and AA administration were predefined as the subgroups. RESULTS Thirteen studies involving 2414 patients were included in the meta-analysis. ICI and AA therapy had significantly higher ORR than either monotherapy (OR [95% CI]: 0.61 [0.50-0.74]; p < 0.001; I2 = 29%). PFS and OS were favorable benefits in ICI and AA therapy; however, significant heterogeneity was identified in these analyses (I2 = 80% and 59%, respectively). According to the administration timing and sequence, ICI immediately after AA showed no PFS and OS benefits compared to ICI monotherapy (HR [95 % CI]: 1.54 [1.14-2.08] and 1.50 [1.04-2.15], respectively), whereas favorable PFS and OS were demonstrated when AA was concomitantly administered with ICI (HR [95 % CI]: 0.57 [0.43-0.76] and 0.80 [0.61-1.05], respectively) or when AA was administered immediately after ICI (HR [95 % CI]: 0.58 [0.34-1.00] and 0.56 [0.40-0.80], respectively). CONCLUSION ICI and AA therapy can provide favorable clinical effects compared to either monotherapy; however, ICI administered immediately after AA may not show survival benefits.
Collapse
|
|
29
|
Nakagawa K, Kijima T, Okada M, Morise M, Kato M, Hirano K, Fujimoto N, Takenoyama M, Yokouchi H, Ohe Y, Hida T, Aoe K, Kishimoto T, Hirokawa M, Matsuki H, Kaneko Y, Yamada T, Morimoto C, Takeda M. Phase 2 Study of YS110, a Recombinant Humanized Anti-CD26 Monoclonal Antibody, in Japanese Patients With Advanced Malignant Pleural Mesothelioma. JTO Clin Res Rep 2021; 2:100178. [PMID: 34590026 PMCID: PMC8474437 DOI: 10.1016/j.jtocrr.2021.100178] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/07/2020] [Revised: 04/07/2021] [Accepted: 04/17/2021] [Indexed: 01/21/2023] Open
Abstract
Introduction YS110, a humanized monoclonal antibody with a high affinity to CD26, exhibited promising antitumor activity and was generally well-tolerated in the phase 1 part of a phase 1 and 2 Japanese trial in patients with malignant pleural mesothelioma (MPM). Here we report the results of the phase 2 part of the study. Methods The patients included were aged 20 years and older, had histologically confirmed MPM, were refractory to or intolerant of existing antineoplastic agents, and were not candidates for standard therapy. YS110 6 mg/kg, determined in the phase 1 dose-determination part, was given in 6-weekly cycles (5 × once-weekly infusions, followed by a 1-wk rest). Results The study included 31 patients (median age = 68 y, 90.3% men); 64.5% had stage IV MPM, 90.3% had greater than or equal to 20% CD26 expression in tumor tissue, and 38.7% (12 patients) had previously received nivolumab. The 6-month disease control rate was 3.2%. The best overall response was partial response in one patient and stable disease in 14 patients. The median progression-free survival was 2.8 months (both in patients who had and had not previously received nivolumab—groups A and B, respectively). Respective progression-free survival rates at 6 months were 9.1% and 31.6% in groups A and B. The median overall survival was 9.7 months. A total of 30 patients (96.8%) had at least one adverse event. Common treatment-related adverse events were infusion-related reaction (16.1%), hiccups (9.7%), and interstitial lung disease (9.7%). There were no treatment-related deaths. Conclusions The 6-month disease control rate did not exceed the predefined threshold, but YS110 revealed modest efficacy in response rate as salvage therapy in difficult-to-treat patients with MPM. YS110 was generally well tolerated.
Collapse
Affiliation(s)
- Kazuhiko Nakagawa
- Department of Medical Oncology, Kindai University Faculty of Medicine, Osaka-Sayama, Japan
| | - Takashi Kijima
- Department of Respiratory Medicine and Hematology, Hyogo College of Medicine, Nishinomiya City, Japan
| | - Morihito Okada
- Department of Surgical Oncology, Hiroshima University, Hiroshima City, Japan
| | - Masahiro Morise
- Department of Respiratory Medicine, Nagoya University Graduate School of Medicine, Nagoya City, Japan
| | - Motoyasu Kato
- Department of Respiratory Medicine, Juntendo University Graduate School of Medicine, Tokyo, Japan
| | - Katsuya Hirano
- Department of Respiratory Medicine, Hyogo Prefectural Amagasaki General Medical Center, Amagasaki City, Japan
| | - Nobukazu Fujimoto
- Department of Medical Oncology, Okayama Rosai Hospital, Okayama City, Japan
| | - Mitsuhiro Takenoyama
- Department of Thoracic Oncology, National Hospital Organization Kyushu Cancer Center, Fukuoka City, Japan
| | - Hiroshi Yokouchi
- Department of Respiratory Medicine, National Hospital Organization Hokkaido Cancer Center, Sapporo City, Japan
| | - Yuichiro Ohe
- Department of Thoracic Oncology, National Cancer Center Hospital, Tokyo, Japan
| | - Toyoaki Hida
- Department of Thoracic Oncology, Aichi Cancer Center Hospital, Nagoya City, Japan
| | - Keisuke Aoe
- Department of Medical Oncology, National Hospital Organization Yamaguchi-Ube Medical Center, Ube City, Japan
| | - Takumi Kishimoto
- Research & Training Center for Asbestos-Related Diseases, Okayama City, Japan
| | | | | | | | - Taketo Yamada
- Department of Pathology, Saitama Medical University, Iruma-gun, Japan
| | - Chikao Morimoto
- Department of Therapy Development and Innovation for Immune Disorders and Cancers, Graduate School of Medicine, Juntendo University, Tokyo, Japan
| | - Masayuki Takeda
- Department of Medical Oncology, Kindai University Faculty of Medicine, Osaka-Sayama, Japan
| |
Collapse
|
|
30
|
Brueckl WM, Reck M, Rittmeyer A, Kollmeier J, Wesseler C, Wiest GH, Christopoulos P, Stenzinger A, Tufman A, Hoffknecht P, Ulm B, Reich F, Ficker JH, Laack E. Efficacy of docetaxel plus ramucirumab as palliative second-line therapy following first-line chemotherapy plus immune-checkpoint-inhibitor combination treatment in patients with non-small cell lung cancer (NSCLC) UICC stage IV. Transl Lung Cancer Res 2021; 10:3093-3105. [PMID: 34430350 PMCID: PMC8350088 DOI: 10.21037/tlcr-21-197] [Citation(s) in RCA: 27] [Impact Index Per Article: 6.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/11/2021] [Accepted: 05/25/2021] [Indexed: 12/26/2022]
Abstract
Background Chemotherapy plus immune-checkpoint inhibitor (CTx+ICI) therapy has become the preferred 1st line treatment in patients with metastatic NSCLC without oncogenic driven mutations. However, the optimal subsequent 2nd line treatment is not defined and several alternatives exist. The purpose of this analysis was to evaluate the efficacy of 2nd line docetaxel plus ramucirumab (D+R) initiated after failure of 1st line CTx+ICI. Methods Retrospective data were collected during routine care from German thoracic oncology centers. Only patients who had received at least one course of 2nd line D+R were included. ORR, PFS, OS and numbers of courses of D+R were investigated with PFS after initiation of D+R being the primary endpoint. Results Seventy-seven patients met the inclusion criteria. 2nd line treatment with D+R achieved an ORR and DCR of 32.5% and 62.4%, respectively. Median PFS for 2nd line therapy was 3.9 months with a DOR of 6.4 months. Median OS of 15.5 and 7.5 months were observed from the start of 1st line therapy and 2nd line treatment, respectively. No unexpected toxicities occurred. Presence of KRAS mutations was associated with significantly worse median PFS to D+R (2.8 vs. 4.5 months in wild-type cases; P=0.021) and was an independent predictor of inferior PFS in multivariate analysis. Conclusions D+R is an effective and safe 2nd line treatment after failure of 1st line CTx+ICI irrespective of NSCLC histology. However, patients with a KRAS mutation did not benefit from D+R in terms of PFS and will require further investigations.
Collapse
Affiliation(s)
- Wolfgang M Brueckl
- Department of Respiratory Medicine, Allergology and Sleep Medicine/Nuernberg Lung Cancer Center, Nuernberg General Hospital, Nuremberg, Germany.,Paracelsus Medical University Nuremberg, Nuremberg, Germany
| | - Martin Reck
- Department of Thoracic Oncology, Airway Research Center North, German Center for Lung Research, Lung Clinic, Grosshansdorf, Germany
| | - Achim Rittmeyer
- Lungenfachklinik Immenhausen, Ambulanz für pneumologische Onkologie, Kassel, Germany
| | - Jens Kollmeier
- Helios Klinikum Emil von Behring, Lungenklinik Heckeshorn, Berlin, Germany
| | - Claas Wesseler
- Asklepios Tumorzentrum Hamburg, Klinikum Harburg, Hamburg, Germany
| | - Gunther H Wiest
- Asklepios Tumorzentrum Hamburg, Klinikum Harburg, Hamburg, Germany
| | | | - Albrecht Stenzinger
- Institute of Pathology, University Hospital Heidelberg, Heidelberg, Germany.,German Cancer Consortium (DKTK), Partner Site Heidelberg, and German Cancer Research Center (DKFZ), Heidelberg, Germany
| | - Amanda Tufman
- Medizinische Klinik V, Pneumologie, Klinikum der Universität München, Member of the German Center for Lung Research, CPC-M, Munich, Germany
| | - Petra Hoffknecht
- Lungenzentrum Osnabrueck, Klinik für Thoraxonkologie, Franziskus-Hospital Harderberg, Georgsmarienhütte, Germany
| | - Bernhard Ulm
- Unabhängige statistische Beratung Bernhard Ulm, Munich, Germany
| | - Fabian Reich
- Department of Respiratory Medicine, Allergology and Sleep Medicine/Nuernberg Lung Cancer Center, Nuernberg General Hospital, Nuremberg, Germany.,Paracelsus Medical University Nuremberg, Nuremberg, Germany
| | - Joachim H Ficker
- Department of Respiratory Medicine, Allergology and Sleep Medicine/Nuernberg Lung Cancer Center, Nuernberg General Hospital, Nuremberg, Germany.,Paracelsus Medical University Nuremberg, Nuremberg, Germany
| | | |
Collapse
|
|
31
|
Takemoto S, Akagi K, Ono S, Tomono H, Honda N, Suyama T, Umeyama Y, Dotsu Y, Taniguchi H, Ogawara D, Senju H, Gyotoku H, Sugasaki N, Yamaguchi H, Nakatomi K, Fukuda M, Mukae H. Efficacy of S-1 after pemetrexed in patients with non-small cell lung cancer: A retrospective multi-institutional analysis. Thorac Cancer 2021; 12:2300-2306. [PMID: 34255933 PMCID: PMC8410557 DOI: 10.1111/1759-7714.14055] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/28/2021] [Revised: 05/24/2021] [Accepted: 05/30/2021] [Indexed: 11/26/2022] Open
Abstract
Background S‐1 and pemetrexed (PEM) are key treatments for non‐small cell lung cancer (NSCLC). However, the mechanism of anticancer activity of S‐1 and PEM is similar. Cross‐resistance between S‐1 and PEM is of concern. This exploratory study was designed to evaluate the treatment effect of S‐1 following PEM‐containing treatment. Methods This retrospective study included patients with advanced (c‐stage III or IV, UICC seventh edition) or recurrent NSCLC who received S‐1 monotherapy following the failure of previous PEM‐containing chemotherapy at six hospitals in Japan. The primary endpoint of the study was the overall response rate (ORR). The secondary endpoint was the disease control rate (DCR), time to treatment failure (TTF), progression‐free survival (PFS), and overall survival (OS). Results A total of 53 NSCLC patients met the criteria for inclusion in the study. Forty‐six patients had adenocarcinoma (88.7%) and no patients had squamous cell carcinoma. Thirty‐one patients (58.5%) received the standard S‐1 regimen and 18 patients (34.0%) received the modified S‐1 regimen. ORR was 1.9% (95% confidence interval [CI]: 0.00%–10.1%). Median TTF, PFS, and OS were 65, 84, and 385 days, respectively. Conclusions Although there were several limitations in this study, the ORR of S‐1 after PEM in patients with nonsquamous (non‐SQ) NSCLC was low compared to the historical control. One of the options in the future might be to avoid S‐1 treatment in PEM‐treated patients who need tumor shrinkage.
Collapse
Affiliation(s)
- Shinnosuke Takemoto
- Department of Respiratory Medicine, Nagasaki University Graduate, School of Biomedical Sciences, Nagasaki, Japan
| | - Kazumasa Akagi
- Department of Respiratory Medicine, Japanese Red Cross Nagasaki Genbaku Isahaya Hospital, Nagasaki, Japan
| | - Sawana Ono
- Department of Respiratory Medicine, Japanese Red Cross Nagasaki Genbaku Hospital, Nagasaki, Japan
| | - Hiromi Tomono
- Department of Respiratory Medicine, National Hospital Organization Nagasaki Medical Center, Nagasaki, Japan
| | - Noritaka Honda
- Department of Respiratory Medicine, Nagasaki University Graduate, School of Biomedical Sciences, Nagasaki, Japan
| | - Takayuki Suyama
- Department of Respiratory Medicine, Nagasaki University Graduate, School of Biomedical Sciences, Nagasaki, Japan
| | - Yasuhiro Umeyama
- Department of Respiratory Medicine, Nagasaki University Graduate, School of Biomedical Sciences, Nagasaki, Japan
| | - Yosuke Dotsu
- Department of Respiratory Medicine, Nagasaki University Graduate, School of Biomedical Sciences, Nagasaki, Japan
| | - Hirokazu Taniguchi
- Molecular Pharmacology Program and Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York, USA
| | - Daiki Ogawara
- Department of Respiratory Medicine, Fukuoka Wajiro Hospital, Fukuoka, Japan
| | - Hiroaki Senju
- Department of Respiratory Medicine, Sasebo City General Hospital, Nagasaki, Japan
| | - Hiroshi Gyotoku
- Department of Respiratory Medicine, Nagasaki University Graduate, School of Biomedical Sciences, Nagasaki, Japan
| | - Nanae Sugasaki
- Department of Respiratory Medicine, Nagasaki Prefecture Shimabara Hospital, Nagasaki, Japan
| | - Hiroyuki Yamaguchi
- Department of Respiratory Medicine, Nagasaki University Graduate, School of Biomedical Sciences, Nagasaki, Japan
| | - Katsumi Nakatomi
- Department of Respiratory Medicine, National Hospital Organization Ureshino Medical Center, Saga, Japan
| | - Minoru Fukuda
- Department of Clinical oncology Center, Nagasaki University Hospital, Nagasaki, Japan
| | - Hiroshi Mukae
- Department of Respiratory Medicine, Nagasaki University Graduate, School of Biomedical Sciences, Nagasaki, Japan
| |
Collapse
|
|
32
|
Imai H, Kishikawa T, Minemura H, Yamada Y, Ibe T, Mori K, Yamaguchi O, Mouri A, Hamamoto Y, Kanazawa K, Kasai T, Kaira K, Kaburagi T, Minato K, Kobayashi K, Kagamu H. Post-Progression Survival Influences Overall Survival among Patients with Advanced Non-Small Cell Lung Cancer Undergoing First-Line Pembrolizumab Monotherapy. Oncology 2021; 99:562-570. [PMID: 34237736 DOI: 10.1159/000516745] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/21/2021] [Accepted: 04/16/2021] [Indexed: 11/19/2022]
Abstract
BACKGROUND Among patients with non-small cell lung cancer (NSCLC), the impact of first-line treatment on overall survival (OS) may be influenced by subsequent therapies. Thus, using patient-level data, we assessed the relationships of progression-free survival (PFS) and post-progression survival (PPS) with OS among patients with high-programmed death-ligand 1 (PD-L1) expression undergoing first-line pembrolizumab monotherapy for NSCLC. METHODS We reviewed data from 133 patients with high PD-L1 expression undergoing first-line pembrolizumab monotherapy for NSCLC at 6 Japanese centers between February 2017 and December 2018. The correlations of PFS and PPS with OS were evaluated at the patient level. RESULTS Linear regression analyses and Spearman's rank correlation coefficient revealed that PPS was strongly correlated with OS (r = 0.76, p < 0.05, R2 = 0.65), while PFS was only moderately correlated with OS (r = 0.71, p < 0.05, and R2 = 0.4). Furthermore, PPS was significantly associated with performance status at the end of pembrolizumab monotherapy, as well as the use of platinum-based combination chemotherapy after pembrolizumab monotherapy (both p < 0.05). CONCLUSIONS Among patients with high PD-L1 expression undergoing first-line pembrolizumab monotherapy for NSCLC, PPS was more strongly correlated with OS, relative to the relationship between PFS and OS. Therefore, subsequent treatment appears to significantly influence OS in patients with disease progression following first-line pembrolizumab monotherapy.
Collapse
Affiliation(s)
- Hisao Imai
- Department of Respiratory Medicine, Comprehensive Cancer Center, International Medical Center, Saitama Medical University, Hidaka, Japan.,Division of Respiratory Medicine, Gunma Prefectural Cancer Center, Ota, Japan
| | | | - Hiroyuki Minemura
- Department of Pulmonary Medicine, Fukushima Medical University, Fukushima, Japan
| | - Yutaka Yamada
- Division of Respiratory Medicine, Ibaraki Prefectural Central Hospital, Kasama, Japan
| | - Tatsuya Ibe
- Department of Pulmonary Medicine, National Hospital Organization, Nishisaitama-Chuo National Hospital, Tokorozawa, Japan
| | - Keita Mori
- Clinical Research Support Center, Shizuoka Cancer Center, Nagaizumi, Japan
| | - Ou Yamaguchi
- Department of Respiratory Medicine, Comprehensive Cancer Center, International Medical Center, Saitama Medical University, Hidaka, Japan
| | - Atsuto Mouri
- Department of Respiratory Medicine, Comprehensive Cancer Center, International Medical Center, Saitama Medical University, Hidaka, Japan
| | - Yoichiro Hamamoto
- Department of Pulmonary Medicine, National Hospital Organization, Nishisaitama-Chuo National Hospital, Tokorozawa, Japan
| | - Kenya Kanazawa
- Department of Pulmonary Medicine, Fukushima Medical University, Fukushima, Japan
| | - Takashi Kasai
- Division of Thoracic Oncology, Tochigi Cancer Center, Utsunomiya, Japan
| | - Kyoichi Kaira
- Department of Respiratory Medicine, Comprehensive Cancer Center, International Medical Center, Saitama Medical University, Hidaka, Japan
| | - Takayuki Kaburagi
- Division of Respiratory Medicine, Ibaraki Prefectural Central Hospital, Kasama, Japan
| | - Koichi Minato
- Division of Respiratory Medicine, Gunma Prefectural Cancer Center, Ota, Japan
| | - Kunihiko Kobayashi
- Department of Respiratory Medicine, Comprehensive Cancer Center, International Medical Center, Saitama Medical University, Hidaka, Japan
| | - Hiroshi Kagamu
- Department of Respiratory Medicine, Comprehensive Cancer Center, International Medical Center, Saitama Medical University, Hidaka, Japan
| |
Collapse
|
|
33
|
Tomita Y, Kimura G, Fukasawa S, Numakura K, Sugiyama Y, Yamana K, Naito S, Kabu K, Tajima Y, Oya M. Efficacy and safety of subsequent molecular targeted therapy after immuno-checkpoint therapy, retrospective study of Japanese patients with metastatic renal cell carcinoma (AFTER I-O study). Jpn J Clin Oncol 2021; 51:966-975. [PMID: 33594427 PMCID: PMC8163064 DOI: 10.1093/jjco/hyaa266] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/04/2020] [Accepted: 12/22/2020] [Indexed: 12/20/2022] Open
Abstract
Objectives Guidelines for treatment of mRCC recommend nivolumab monotherapy (NIVO) for treated patients, and nivolumab plus ipilimumab combination therapy (NIVO+IPI) for untreated IMDC intermediate and poor-risk mRCC patients. Although molecular-targeted therapies (TTs) such as VEGFR-TKIs and mTORi are recommended as subsequent therapy after NIVO or NIVO+IPI, their efficacy and safety remain unclear. Methods Outcome of Japanese patients with mRCC who received TT after NIVO (CheckMate 025) or NIVO+IPI (CheckMate 214) were retrospectively analyzed. Primary endpoints were investigator-assessed ORR of the first TT after either NIVO or NIVO+IPI. Secondary endpoints included TFS, PFS, OS and safety of TTs. Results Twenty six patients in CheckMate 025 and 19 patients in CheckMate 214 from 20 centers in Japan were analyzed. As the first subsequent TT after NIVO or NIVO+IPI, axitinib was the most frequently treated regimen for both CheckMate 025 (54%) and CheckMate 214 (47%) patients. The ORRs of TT after NIVO and NIVO+IPI were 27 and 32% (all risks), and median PFSs were 8.9 and 16.3 months, respectively. During the treatment of first TT after either NIVO or NIVO+IPI, 98% of patients experienced treatment-related adverse events, including grade 3–4 events in 51% of patients, and no treatment-related deaths occurred. Conclusions TTs have favorable antitumor activity in patients with mRCC after ICI, possibly via changing the mechanism of action. Safety signals of TTs after ICI were similar to previous reports. These results indicate that sequential TTs after ICI may contribute for long survival benefit.
Collapse
Affiliation(s)
- Yoshihiko Tomita
- Department of Urology, Molecular Oncology, Graduate School of Medicine and Dental Sciences, Niigata, Japan
| | - Go Kimura
- Department of Urology, Nippon Medical School Hospital, Tokyo, Japan
| | | | - Kazuyuki Numakura
- Department of Urology, Akita University School of Medicine, Akita, Japan
| | - Yutaka Sugiyama
- Department of Urology, Graduate School of Medical Sciences, Kumamoto, Japan
| | - Kazutoshi Yamana
- Department of Urology, Molecular Oncology, Graduate School of Medicine and Dental Sciences, Niigata, Japan
| | - Sei Naito
- Department of Urology, Yamagata University Faculty of Medicine, Yamagata, Japan
| | - Koki Kabu
- Bristol-Myers Squibb, Shinjuku-ku, Tokyo, Japan
| | | | - Mototsugu Oya
- Department of Urology, Keio University School of Medicine, Tokyo, Japan
| |
Collapse
|
|
34
|
Narita Y, Shoji H, Kawai S, Mizukami T, Nakamura M, Moriwaki T, Yamanaka T, Sunakawa Y, Kawakami H, Nishina T, Misumi T, Muro K. REVIVE study: a prospective observational study in chemotherapy after nivolumab therapy for advanced gastric cancer. Future Oncol 2021; 17:869-875. [PMID: 32954810 DOI: 10.2217/fon-2020-0621] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/15/2020] [Accepted: 08/18/2020] [Indexed: 01/11/2023] Open
Abstract
Nivolumab is an increasingly used standard care treatment for heavily pretreated patients with advanced gastric cancer, with increasing clinical use in Japan. Data from retrospective studies on various tumors have shown the objective response rate to cytotoxic chemotherapy potentially improves after an exposure to immune checkpoint inhibitors. Based on these data, we conducted the multicenter observational REVIVE study to evaluate the efficacy and safety of cytotoxic chemotherapy in nivolumab-refractory or nivolumab-intolerant patients with advanced gastric cancer. Patients who are refractory or intolerant to nivolumab and scheduled to receive irinotecan monotherapy, oxaliplatin combination treatment or oral trifluridine/tipiracil hydrochloride therapy will be included. The primary end point is overall survival of nivolumab-pretreated patients with advanced gastric cancer after the cytotoxic chemotherapy. Clinical trial registration: UMIN000032182 (umin.ac.jp).
Collapse
Affiliation(s)
- Yukiya Narita
- Department of Clinical Oncology, Aichi Cancer Center Hospital, Nagoya, 464-8681, Japan
| | - Hirokazu Shoji
- Department of Gastrointestinal Medical Oncology, National Cancer Center Hospital, Tokyo, 104-0045, Japan
| | - Sadayuki Kawai
- Department of Medical Oncology, Shizuoka General Hospital, Shizuoka, 420-5827, Japan
| | - Takuro Mizukami
- Department of Clinical Oncology, St Marianna University School of Medicine, Kawasaki, 216-8511, Japan
| | - Michio Nakamura
- Department of Gastroenterology, Sapporo City General Hospital, Sapporo, 060-8604, Japan
| | - Toshikazu Moriwaki
- Division of Gastroenterology, Faculty of Medicine, University of Tsukuba, Tsukuba, 305-8577, Japan
| | - Takeharu Yamanaka
- Department of Biostatistics, Yokohama City University School of Medicine, Yokohama, 236-0004, Japan
| | - Yu Sunakawa
- Department of Clinical Oncology, St Marianna University School of Medicine, Kawasaki, 216-8511, Japan
| | - Hisato Kawakami
- Department of Medical Oncology, Kindai University Faculty of Medicine, Osakasayama, 577-8502, Japan
| | - Tomohiro Nishina
- Department of Gastrointestinal Medical Oncology, National Hospital Organization Shikoku Cancer Center, Matsuyama, 791-0280, Japan
| | - Toshihiro Misumi
- Department of Biostatistics, Yokohama City University School of Medicine, Yokohama, 236-0004, Japan
| | - Kei Muro
- Department of Clinical Oncology, Aichi Cancer Center Hospital, Nagoya, 464-8681, Japan
| |
Collapse
|
|
35
|
Furuya N, Nishino M, Wakuda K, Ikeda S, Sato T, Ushio R, Tanzawa S, Sata M, Ito K. Real-world efficacy of atezolizumab in non-small cell lung cancer: A multicenter cohort study focused on performance status and retreatment after failure of anti-PD-1 antibody. Thorac Cancer 2021; 12:613-618. [PMID: 33448648 PMCID: PMC7919123 DOI: 10.1111/1759-7714.13824] [Citation(s) in RCA: 25] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/28/2020] [Revised: 12/22/2020] [Accepted: 12/22/2020] [Indexed: 11/28/2022] Open
Abstract
Background Atezolizumab is a programmed death‐ligand 1 (PD‐L1) targeted monoclonal antibody that inhibits PD‐L1 interacting with its receptors PD‐1 and B7‐1, thereby enhancing anticancer immunity. Some real‐world efficacy and safety studies of anti‐PD‐1 antibody have been previously reported. However, there have been no reports investigating the efficacy of atezolizumab monotherapy in clinical practice which have focused on performance status and previous anti‐PD‐1 antibody treatment. Methods We retrospectively reviewed consecutive advanced NSCLC patients who received atezolizumab monotherapy between April 2018 and February 2019 at eight institutions. A total of 152 patients with NSCLC were enrolled in this study. Results A total of 38 patients (25%) had already been treated with anti‐PD‐1 treatment (nivolumab or pembrolizumab) before atezolizumab. The median OS and TTF was 384 days (12.8 months) (95% confidence interval [CI]: 206–424), and 42 days (1.4 months) (95% CI: 27–56) in all patients, respectively. ECOG PS 0 had significantly longer OS (median OS; not reached, p < 0.0001) and TTF (median TTF; 63 days, p = 0.012) compared with PS 1 or 2–3. Most retreated patients were unable to continue atezolizumab for a longer period, but seven patients (18.4%) were able to continue atezolizumab over four months as an ICI retreatment. Conclusions In previously treated advanced NSCLC patients, atezolizumab monotherapy demonstrated good efficacy and safety regardless of heavily treated patients in real‐world clinical practice, and ECOG PS 0 was a favorable predictive factor. The efficacy of retreatment with atezolizumab was limited but was well tolerated in patients treated with prior anti‐PD‐1 antibody.
Collapse
Affiliation(s)
- Naoki Furuya
- Division of Respiratory Medicine, Department of Internal Medicine, St. Marianna University School of Medicine, Kawasaki, Japan
| | - Makoto Nishino
- Department of Experimental Therapeutics, National Cancer Center Hospital, Tokyo, Japan.,Division of Pulmonary Medicine, Department of Medicine, Keiyu Hospital, Yokohama, Japan
| | - Kazushige Wakuda
- Division of Thoracic Oncology, Shizuoka Cancer Center, Shizuoka, Japan
| | - Satoshi Ikeda
- Department of Respiratory Medicine, Kanagawa Cardiovascular and Respiratory Center, Yokohama, Japan
| | - Takashi Sato
- Division of Pulmonary Medicine, Department of Medicine, Keiyu Hospital, Yokohama, Japan
| | - Ryota Ushio
- Respiratory Disease Center, Yokohama City University Medical Center, Yokohama, Japan
| | - Shigeru Tanzawa
- Division of Medical Oncology, Department of Internal Medicine, Teikyo University School of Medicine, Tokyo, Japan
| | - Masafumi Sata
- Division of Pulmonary Medicine, Department of Medicine, Jichi Medical University, Tochigi, Japan
| | - Kentaro Ito
- Respiratory Center, Matsusaka Municipal Hospital, Matsusaka, Japan
| |
Collapse
|
|
36
|
Lopez-Beltran A, Cimadamore A, Blanca A, Massari F, Vau N, Scarpelli M, Cheng L, Montironi R. Immune Checkpoint Inhibitors for the Treatment of Bladder Cancer. Cancers (Basel) 2021; 13:E131. [PMID: 33401585 PMCID: PMC7795541 DOI: 10.3390/cancers13010131] [Citation(s) in RCA: 183] [Impact Index Per Article: 45.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/10/2020] [Revised: 12/28/2020] [Accepted: 12/30/2020] [Indexed: 12/11/2022] Open
Abstract
A number of immune checkpoint inhibitors (ICIs) have been approved as first-line therapy in case of cisplatin-ineligible patients or as second-line therapy for patients with metastatic urothelial carcinoma (mUC) of the bladder. About 30% of patients with mUC will respond to ICIs immunotherapy. Programmed death-ligand 1 (PD-L1) expression detected by immunohistochemistry seems to predict response to immune checkpoint inhibitors in patients with mUC as supported by the objective response rate (ORR) and overall survival (OS) associated with the response observed in most clinical trials. Pembrolizumab, an anti-PD-1 antibody, demonstrated better OS respective to chemotherapy in a randomized phase 3 study for second-line treatment of mUC. Nivolumab, a PD-1 antibody, also demonstrated an OS benefit when compared to controls. Atezolizumab, Durvalumab, and Avelumab antibodies targeting PD-L1 have also received approval as second-line treatments for mUC with durable response for more than 1 year in selected patients. Atezolizumab and Pembrolizumab also received approval for first-line treatment of patients that are ineligible for cisplatin. A focus on the utility of ICIs in the adjuvant or neoadjuvant setting, or as combination with chemotherapy, is the basis of some ongoing trials. The identification of a clinically useful biomarker, single or in association, to determine the optimal ICIs treatment for patients with mUC is very much needed as emphasized by the current literature. In this review, we examined relevant clinical trial results with ICIs in patients with mUC alone or as part of drug combinations; emphasis is also placed on the adjuvant and neoadjuvant setting. The current landscape of selected biomarkers of response to ICIs including anti-PD-L1 immunohistochemistry is also briefly reviewed.
Collapse
Affiliation(s)
- Antonio Lopez-Beltran
- Unit of Anatomic Pathology, Department of Morphological Sciences, Cordoba University Medical School, 14004 Cordoba, Spain
| | - Alessia Cimadamore
- Pathological Anatomy, School of Medicine, United Hospitals, Polytechnic University of the Marche Region, 60126 Ancona, Italy; (A.C.); (M.S.)
| | - Ana Blanca
- Maimonides Biomedical Research Institute of Cordoba, Department of Urology, University Hospital of Reina Sofia, 14004 Cordoba, Spain;
| | - Francesco Massari
- Division of Oncology, IRCCS Azienda Ospedaliero-Universitaria di Bologna, 40138 Bologna, Italy;
| | - Nuno Vau
- Medical Oncology, Champalimaud Clinical Center, 1400-038 Lisbon, Portugal;
| | - Marina Scarpelli
- Pathological Anatomy, School of Medicine, United Hospitals, Polytechnic University of the Marche Region, 60126 Ancona, Italy; (A.C.); (M.S.)
| | - Liang Cheng
- Department of Pathology and Laboratory Medicine, School of Medicine, Indiana University, Indianapolis, IN 46202, USA;
| | - Rodolfo Montironi
- Pathological Anatomy, School of Medicine, United Hospitals, Polytechnic University of the Marche Region, 60126 Ancona, Italy; (A.C.); (M.S.)
| |
Collapse
|
|
37
|
Kurosaki T, Mitani S, Tanaka K, Suzuki S, Kanemura H, Haratani K, Fumita S, Iwasa T, Hayashi H, Yoshida T, Ishikawa K, Kitano M, Otsuki N, Nishimura Y, Doi K, Nakagawa K. Safety and efficacy of cetuximab-containing chemotherapy after immune checkpoint inhibitors for patients with squamous cell carcinoma of the head and neck: a single-center retrospective study. Anticancer Drugs 2021; 32:95-101. [PMID: 32976215 PMCID: PMC7748051 DOI: 10.1097/cad.0000000000001006] [Citation(s) in RCA: 22] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/12/2020] [Revised: 09/09/2020] [Accepted: 09/09/2020] [Indexed: 12/24/2022]
Abstract
Immunotherapy has been shown to prolong survival in recurrent or metastatic squamous cell carcinoma of the head and neck (SCCHN) in front-line use; however, subsequent systemic therapy has not been optimized. This study aimed to evaluate the safety and efficacy of cetuximab-containing chemotherapy after immunotherapy. We retrospectively analyzed patients with recurrent or metastatic SCCHN who underwent cetuximab-containing regimens after progression on immunotherapy. Of the 22 patients who met the inclusion criteria, 21 received paclitaxel and cetuximab, and 1 carboplatin and fluorouracil and cetuximab after immunotherapy. Nine patients achieved a partial response, 10 patients had stable disease as their best response on cetuximab-containing chemotherapy, yielding an overall response rate and disease control rate of 40.9 and 86.4%, respectively. The median progression-free survival was 5.2 months, and the median overall survival was 14.5 months. Ten patients developed grade 3-4 adverse events, including neutropenia (31.8%), acneiform rash (9.1%), anemia (4.5%), hypertransaminasemia (4.5%) and stomatitis (4.5%). The most frequent cetuximab-related toxicities across all grades were skin reactions (77.3%), hypomagnesemia (40.9%), stomatitis (27.3%), paronychia (13.6%) and keratitis (4.5%). There was no treatment-related death. Taken together, cetuximab-containing chemotherapy was effective and feasible even after immunotherapy.
Collapse
Affiliation(s)
| | | | | | | | | | | | | | | | | | | | | | - Mutsukazu Kitano
- Department of Otolaryngology, Kindai University Faculty of Medicine, Osaka-Sayama, Osaka, Japan
| | - Naoki Otsuki
- Department of Otolaryngology, Kindai University Faculty of Medicine, Osaka-Sayama, Osaka, Japan
| | | | - Katsumi Doi
- Department of Otolaryngology, Kindai University Faculty of Medicine, Osaka-Sayama, Osaka, Japan
| | | |
Collapse
|
|
38
|
Bersanelli M, Buti S, Giannarelli D, Leonetti A, Cortellini A, Russo GL, Signorelli D, Toschi L, Milella M, Pilotto S, Bria E, Proto C, Marinello A, Randon G, Rossi S, Vita E, Sartori G, D'Argento E, Qako E, Giaiacopi E, Ghilardi L, Bettini AC, Rapacchi E, Mazzoni F, Lavacchi D, Scotti V, Ciccone LP, De Tursi M, Di Marino P, Santini D, Russano M, Bordi P, Di Maio M, Audisio M, Filetti M, Giusti R, Berardi R, Fiordoliva I, Cerea G, Pizzutilo EG, Bearz A, De Carlo E, Cecere F, Renna D, Camisa R, Caruso G, Ficorella C, Banna GL, Cortinovis D, Brighenti M, Garassino MC, Tiseo M. Chemotherapy in non-small cell lung cancer patients after prior immunotherapy: The multicenter retrospective CLARITY study. Lung Cancer 2020; 150:123-131. [PMID: 33130353 DOI: 10.1016/j.lungcan.2020.10.008] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/27/2020] [Revised: 10/11/2020] [Accepted: 10/14/2020] [Indexed: 12/14/2022]
Abstract
OBJECTIVES In the most of cases, for non-small cell lung cancer (NSCLC) patients who progressed to previous immune checkpoint inhibitors (CKI) administered as first- or as second-line therapy, chemotherapy (CT) remains the only viable options in the absence of "druggable" mutations. We aimed to explore the efficacy of salvage chemotherapy after immunotherapy (SCAI) in advanced NSCLC patients. MATERIALS AND METHODS We designed a retrospective, multicenter study, involving 20 Italian centers, with the primary objective of describing the clinical outcome of advanced NSCLC patients treated with SCAI at the participating institutions from November 2013 to July 2019. The primary endpoint of the study was represented by overall survival (OS), defined as the time from CT initiation to death. Secondary outcome endpoints of the SCAI (progression free survival, PFS, objective response rate, ORR and toxicity) and explorative biomarkers (lactate dehydrogenase, LDH, and neutrophil-to-lymphocyte ratio, NLR during immunotherapy) were also analyzed. RESULTS In our study population of 342 NSCLC patients, SCAI obtained a median OS of 6.8 months (95 % confidence interval, CI 5.5-8.1), median PFS of 4.1 months (95 % CI 3.4-4.8) and ORR of 22.8 %. A "Post-CKI score" was constructed by combining significant predictors of OS at the multivariate analyses (sex, ECOG PS, disease control with prior immunotherapy), Harrell'C was 0.65, (95 % CI:0.59-0.71). CONCLUSIONS Despite the late-line settings, our findings support the hypothesis that previous immunotherapy might increase the sensitivity of the tumor to the subsequent chemotherapy. The "Post-CKI score" was clinically effective in successfully discriminating three distinct prognostic subgroups of patients after the failure of CKI, representing a possibly useful tool for the tailored decision-making process of advanced treatment-line settings in NSCLC.
Collapse
Affiliation(s)
- Melissa Bersanelli
- Medicine and Surgery Department, University of Parma, Parma, Italy; Medical Oncology Unit, University Hospital of Parma, Parma, Italy.
| | - Sebastiano Buti
- Medical Oncology Unit, University Hospital of Parma, Parma, Italy
| | - Diana Giannarelli
- Regina Elena National Cancer Institute, IRCCS, Biostatistical Unit, Roma, Italy
| | - Alessandro Leonetti
- Medicine and Surgery Department, University of Parma, Parma, Italy; Medical Oncology Unit, University Hospital of Parma, Parma, Italy
| | - Alessio Cortellini
- Department of Biotechnology and Applied Clinical Science, University of L'Aquila, L'Aquila, Italy; Medical Oncology, St. Salvatore Hospital, L'Aquila, Italy
| | - Giuseppe Lo Russo
- Oncologia Toracica, Dipartimento di Oncologia Medica, Fondazione IRCCS Istituto Nazionale dei Tumori di Milano, Italy
| | - Diego Signorelli
- Oncologia Toracica, Dipartimento di Oncologia Medica, Fondazione IRCCS Istituto Nazionale dei Tumori di Milano, Italy
| | - Luca Toschi
- Medical Oncology, Humanitas Clinical and Research Center - IRCCS, Rozzano, Milano, Italy
| | - Michele Milella
- Section of Oncology, Department of Medicine, University of Verona School of Medicine and Verona University Hospital Trust, Verona, Italy
| | - Sara Pilotto
- Section of Oncology, Department of Medicine, University of Verona School of Medicine and Verona University Hospital Trust, Verona, Italy
| | - Emilio Bria
- Comprehensive Cancer Center, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, and Dipartimento di Medicina e Chirurgia Traslazionale, Università Cattolica del Sacro Cuore, Roma, Italy
| | - Claudia Proto
- Oncologia Toracica, Dipartimento di Oncologia Medica, Fondazione IRCCS Istituto Nazionale dei Tumori di Milano, Italy
| | - Arianna Marinello
- Medical Oncology, Humanitas Clinical and Research Center - IRCCS, Rozzano, Milano, Italy
| | - Giovanni Randon
- Oncologia Toracica, Dipartimento di Oncologia Medica, Fondazione IRCCS Istituto Nazionale dei Tumori di Milano, Italy
| | - Sabrina Rossi
- Medical Oncology, Humanitas Clinical and Research Center - IRCCS, Rozzano, Milano, Italy
| | - Emanuele Vita
- Comprehensive Cancer Center, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, and Dipartimento di Medicina e Chirurgia Traslazionale, Università Cattolica del Sacro Cuore, Roma, Italy
| | - Giulia Sartori
- Section of Oncology, Department of Medicine, University of Verona School of Medicine and Verona University Hospital Trust, Verona, Italy
| | - Ettore D'Argento
- Comprehensive Cancer Center, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, and Dipartimento di Medicina e Chirurgia Traslazionale, Università Cattolica del Sacro Cuore, Roma, Italy
| | - Eva Qako
- Medicine and Surgery Department, University of Parma, Parma, Italy
| | - Elisa Giaiacopi
- Medicine and Surgery Department, University of Parma, Parma, Italy
| | - Laura Ghilardi
- UO di Oncologia medica, ASST PAPA Giovanni XXIII Bergamo, Italy
| | | | - Elena Rapacchi
- Medical Oncology Unit, University Hospital of Parma, Parma, Italy
| | | | - Daniele Lavacchi
- Oncology Department, Careggi University Hospital, Firenze, Italy
| | - Vieri Scotti
- Radiation Oncology Unit, Oncology Department, Azienda Ospedaliero-Universitaria Careggi, Firenze, Italy
| | - Lucia Pia Ciccone
- Radiation Oncology Unit, Oncology Department, Azienda Ospedaliero-Universitaria Careggi, Firenze, Italy
| | - Michele De Tursi
- Dipartimento di Scienze mediche, orali e biotecnologiche, Sezione di Oncologia, Università G. D'Annunzio, Chieti, Italy
| | - Pietro Di Marino
- Dipartimento di Scienze mediche, orali e biotecnologiche, Sezione di Oncologia, Università G. D'Annunzio, Chieti, Italy
| | | | - Marco Russano
- Oncologia Medica, Università Campus Bio-Medico, Roma, Italy
| | - Paola Bordi
- Medical Oncology Unit, University Hospital of Parma, Parma, Italy
| | - Massimo Di Maio
- Department of Oncology, University of Turin, AO Ordine Mauriziano Hospital, Torino, Italy
| | - Marco Audisio
- Department of Oncology, University of Turin, AO Ordine Mauriziano Hospital, Torino, Italy
| | - Marco Filetti
- Medical Oncology Unit, Azienda Ospedaliero-Universitaria Sant'Andrea, Roma, Italy
| | - Raffaele Giusti
- Medical Oncology Unit, Azienda Ospedaliero-Universitaria Sant'Andrea, Roma, Italy
| | - Rossana Berardi
- Clinica Oncologica, Università Politecnica delle Marche - Ospedali Riuniti, Ancona, Italy
| | - Ilaria Fiordoliva
- Clinica Oncologica, Università Politecnica delle Marche - Ospedali Riuniti, Ancona, Italy
| | - Giulio Cerea
- Niguarda Cancer Center, Grande Ospedale Metropolitano Niguarda, Milano, Italy
| | | | | | - Elisa De Carlo
- Centro di Riferimento Oncologico, CRO-IRCCS, Aviano, Italy
| | - Fabiana Cecere
- Regina Elena National Cancer Institute, IRCCS, Oncology Unit, Roma, Italy
| | - Davide Renna
- Regina Elena National Cancer Institute, IRCCS, Oncology Unit, Roma, Italy
| | - Roberta Camisa
- Medical Oncology Unit, University Hospital of Parma, Parma, Italy
| | - Giuseppe Caruso
- Medical Oncology Unit, University Hospital of Parma, Parma, Italy
| | - Corrado Ficorella
- Department of Biotechnology and Applied Clinical Science, University of L'Aquila, L'Aquila, Italy; Medical Oncology, St. Salvatore Hospital, L'Aquila, Italy
| | | | | | | | - Marina Chiara Garassino
- Oncologia Toracica, Dipartimento di Oncologia Medica, Fondazione IRCCS Istituto Nazionale dei Tumori di Milano, Italy
| | - Marcello Tiseo
- Medicine and Surgery Department, University of Parma, Parma, Italy; Medical Oncology Unit, University Hospital of Parma, Parma, Italy
| |
Collapse
|
|
39
|
Nozawa K, Narita Y, Hosoda W, Muro K. Dramatic Response in a Patient with Metastatic Gastric Cancer Using Trifluridine/Tipiracil after Rapid Disease Progression while on Nivolumab. Case Rep Oncol 2020; 13:1381-1386. [PMID: 33442359 PMCID: PMC7772847 DOI: 10.1159/000510405] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/21/2020] [Accepted: 07/23/2020] [Indexed: 12/24/2022] Open
Abstract
The introduction of immune checkpoint inhibitors has redefined the treatment strategy and changed the way tumor assessments are made because of its response pattern. Studies have suggested that initiating chemotherapy after checkpoint inhibitors may have high anti-tumor activity in some cancer types. This response pattern has not been reported in patients with gastric cancer, and particularly for the combination of trifluridine/tipiracil. A 69-year-old man presented at follow-up for metastatic gastric cancer being treated with nivolumab, an anti-PD-1 antibody. Computed tomography of the liver showed a rapid 4-fold growth of the metastasis compared with baseline measurements taken while receiving paclitaxel and ramucirumab. It met the definition of a phenomenon called hyperprogressive disease. Nivolumab was discontinued, and he was switched to trifluridine/tipiracil. The liver metastasis was shrunk markedly after 2 months with improvement in his performance status and laboratory data. Sequential therapy starting with immune checkpoint inhibitors followed by cytotoxic agents such as trifluridine/tipiracil may have an apparent efficacy in gastric cancer even though prior immunotherapy demonstrates hyperprogressive disease.
Collapse
Affiliation(s)
- Kazuki Nozawa
- Department of Clinical Oncology, Aichi Cancer Center Hospital, Nagoya, Japan
| | - Yukiya Narita
- Department of Clinical Oncology, Aichi Cancer Center Hospital, Nagoya, Japan
| | - Waki Hosoda
- Department of Pathology and Molecular Diagnostics, Aichi Cancer Center Hospital, Nagoya, Japan
| | - Kei Muro
- Department of Clinical Oncology, Aichi Cancer Center Hospital, Nagoya, Japan
| |
Collapse
|
|
40
|
Li S, Chu X, Ye L, Ni J, Zhu Z. A narrative review of synergistic drug administration in unresectable locally advanced non-small cell lung cancer: current landscape and future prospects in the era of immunotherapy. Transl Lung Cancer Res 2020; 9:2082-2096. [PMID: 33209628 PMCID: PMC7653136 DOI: 10.21037/tlcr-20-512] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/25/2020] [Accepted: 07/25/2020] [Indexed: 12/25/2022]
Abstract
Based on the PACIFIC study, the standard care of unresectable locally advanced non-small cell lung cancer (LA-NSCLC) shifted from concurrent chemo-radiotherapy (CCRT) alone to CCRT followed by durvalumab consolidation in 2017. In the era of immunotherapy, two kinds of therapeutic drugs are involved in the management of LA-NSCLC: chemotherapeutics and anti-PD-1/PD-L1 agents. However, the best choices of systematic chemotherapy, immunotherapy, and treatment schedule remain controversial. The immune modulation effects of chemotherapy, as well as the potential immunosuppressive impact of pretreatment medications, should be taken into consideration. Indeed, chemotherapeutics are double-edged swords to immunotherapy, with both stimulatory and suppressive effects on the immune system. Moreover, low-dose chemotherapy is reported to enhance anti-tumor immune responses with reduced toxicities. As for glucocorticoids, there is no consensus about its exact impact on the efficacy of immunotherapy. In addition, the timing of anti-PD-1/PD-L1 agent related to CCRT has three modes: induction, concurrent, and consolidation therapy. Although CCRT followed by durvalumab consolidation is the standard of care, the best sequence of immunotherapy and chemo-radiotherapy is still under debate. Furthermore, the efficacy and toxicity of various PD-1/PD-L1 inhibitors should be compared, especially in the background of CCRT. In this review, we will summarize the detailed knowledge about chemotherapeutics and anti-PD-1/PD-L1 axis agents, and discuss the potential implications in designing novel, effective treatment strategies for LA-NSCLC.
Collapse
Affiliation(s)
- Shuyan Li
- Department of Radiation Oncology, Fudan University Shanghai Cancer Center, Shanghai, China
- Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China
| | - Xiao Chu
- Department of Radiation Oncology, Fudan University Shanghai Cancer Center, Shanghai, China
- Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China
| | - Luxi Ye
- Department of Radiation Oncology, Fudan University Shanghai Cancer Center, Shanghai, China
- Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China
| | - Jianjiao Ni
- Department of Radiation Oncology, Fudan University Shanghai Cancer Center, Shanghai, China
- Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China
| | - Zhengfei Zhu
- Department of Radiation Oncology, Fudan University Shanghai Cancer Center, Shanghai, China
- Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China
- Institute of Thoracic Oncology, Fudan University, Shanghai, China
| |
Collapse
|
|
41
|
Brueckl WM, Reck M, Rittmeyer A, Kollmeier J, Wesseler C, Wiest GH, Christopoulos P, Tufman A, Hoffknecht P, Ulm B, Reich F, Ficker JH, Laack E. Efficacy of Docetaxel Plus Ramucirumab as Palliative Third-Line Therapy Following Second-Line Immune-Checkpoint-Inhibitor Treatment in Patients With Non-Small-Cell Lung Cancer Stage IV. Clin Med Insights Oncol 2020; 14:1179554920951358. [PMID: 32884390 PMCID: PMC7440727 DOI: 10.1177/1179554920951358] [Citation(s) in RCA: 24] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/12/2020] [Accepted: 07/23/2020] [Indexed: 12/26/2022] Open
Abstract
BACKGROUND Antiangiogenic agents have been shown to stimulate the immune system and cause synergistic effects with chemotherapy. Effects might be even stronger after immune-checkpoint-inhibitor (ICI) therapy. The purpose of this analysis was to evaluate the efficacy of ramucirumab plus docetaxel (R + D) as third-line treatment after failure of a first-line platinum-based chemotherapy and a second-line ICI treatment in patients with non-small-cell lung cancer (NSCLC) stage IV. METHODS Retrospective data were collected from 9 German thoracic oncology centers. Only patients who had received at least 1 cycle of third-line R + D were included. The numbers of cycles, objective response rate (ORR), progression-free survival (PFS), and overall survival (OS) were investigated. RESULTS Sixty-seven patients met the criteria for inclusion. Third-line treatment with R + D achieved an ORR of 36% and a disease control rate (DCR) of 69%. Median PFS for third-line therapy was 6.8 months with a duration of response (DOR) of 10.2 months. A median OS of 29 months was observed from the start of first-line therapy with a median OS of 11.0 months from the start of third-line treatment. No unexpected toxicities occurred. CONCLUSION R + D is a highly effective and safe third-line treatment after failure of second-line programmed cell death protein 1/programmed cell death-ligand 1 (PD1/PD-L1)-derived ICI therapy irrespective of NSCLC histology. As there may be synergistic effects of second- and third-line treatments, this sequence is a very suitable option for patients not treated with first-line ICI. In addition, R + D should continue to be investigated as a second-line treatment option after failure of chemotherapy plus ICI in the palliative first-line treatment.
Collapse
Affiliation(s)
- Wolfgang M Brueckl
- Nuremberg Lung Cancer Center, Department of Respiratory Medicine, Allergology and Sleep Medicine, General Hospital Nuremberg, Paracelsus Medical University, Nuremberg, Germany
| | - Martin Reck
- LungenClinic Grosshansdorf, Großhansdorf, Germany
| | - Achim Rittmeyer
- Ambulanz für pneumologische Onkologie, Lungenfachklinik Immenhausen, Kassel, Germany
| | - Jens Kollmeier
- Lungenklinik Heckeshorn, Helios Klinikum Emil von Behring, Berlin, Germany
| | - Claas Wesseler
- Asklepios Tumorzentrum Hamburg, Asklepios Klinikum Harburg, Hamburg, Germany
| | - Gunther H Wiest
- Asklepios Tumorzentrum Hamburg, Asklepios Klinikum Harburg, Hamburg, Germany
| | | | - Amanda Tufman
- Medizinische Klinik und Poliklinik V (Pneumologie), Klinikum der Universität München, Munich, Germany
| | - Petra Hoffknecht
- Zentrum Klinik für Thoraxonkologie im Franziskus-Hospital Harderberg, Georgsmarienhütte, Germany
| | - Bernhard Ulm
- Unabhängige statistische Beratung Bernhard Ulm, Munich, Germany
| | - Fabian Reich
- Nuremberg Lung Cancer Center, Department of Respiratory Medicine, Allergology and Sleep Medicine, General Hospital Nuremberg, Paracelsus Medical University, Nuremberg, Germany
| | - Joachim H Ficker
- Nuremberg Lung Cancer Center, Department of Respiratory Medicine, Allergology and Sleep Medicine, General Hospital Nuremberg, Paracelsus Medical University, Nuremberg, Germany
| | - Eckart Laack
- Hämato-Onkologie Hamburg, Praxis, Hamburg, Germany
| |
Collapse
|