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Ding X, Yin X, Zheng L, Zhou L, Hu J, Sun W, Sun L, Shen Y, Teng Y, Xu Y, Li W, Liu M, Chen J. Patients with uHCC and Child-Pugh B8/9 also benefit from a combination of antiangiogenic agents and PD-1 inhibitors: a multicenter real-world study. Acta Oncol 2025; 64:607-615. [PMID: 40325791 PMCID: PMC12067986 DOI: 10.2340/1651-226x.2025.42652] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/05/2024] [Accepted: 04/16/2025] [Indexed: 05/07/2025]
Abstract
BACKGROUND AND PURPOSE Patients with unresectable hepatocellular carcinoma (uHCC) and Child-Pugh grade B face limited treatment options and poor outcomes. This study aims to evaluate whether the effect and safety of combining tyrosine kinase inhibitors (TKIs) with progressive disease (PD)-1 inhibitors in uHCC patients with Child-Pugh B7 (CP7) and B8/9 (CP8/9) differ. METHODS This multicenter retrospective study included 179 uHCC patients with Child-Pugh B (CP7 group: n = 106; CP8/9 group: n = 73), receiving a combination of lenvatinib/sorafenib/other TKIs and PD-1 inhibitors between December 2020 and March 2023. Progression-free survival (PFS) and overall survival (OS) were defined as the primary endpoint. Secondary endpoints included the objective response rate (ORR) and safety. RESULTS The median PFS and OS for the entire cohort were 7.3 months (95% confidence intervals [CI]: 6.3-8.3) and 16.0 months (95% CI: 12.9-19.1), respectively. No statistically significant differences were observed between CP7 and CP8/9 groups in PFS (7.8 vs. 6.3 months, p = 0.28), OS (17.8 vs. 14.0 months, p = 0.20), ORR (33.0% vs. 27.4%, p = 0.42), or safety profiles. However, the CP8/9 group had significantly higher rates of TKI dose reductions (46.6% vs. 31.1%, p = 0.04) and discontinuations (57.5% vs. 24.5%, p < 0.001). Notably, 30.2% of patients maintained sustained radiographic responses despite advanced liver dysfunction. INTERPRETATION Combining TKIs with PD-1 inhibitors is an effective and well-tolerated option for HCC patients with Child-Pugh B, including those with CP8/9.
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Affiliation(s)
- Xiaoyan Ding
- Department of Cancer Center, Beijing Ditan Hospital, Capital Medical University, Beijing, China
| | - Xue Yin
- Department of Cancer Center, Beijing Ditan Hospital, Capital Medical University, Beijing, China
| | - Linlin Zheng
- Jinan Eco-environmental Monitoring Center of Shandong Province, Jinan, Shandong Province, China
| | - Lin Zhou
- Department of Interventional Radiology, The Fifth Medical Center, Chinese PLA General Hospital, Beijing, China
| | - Junke Hu
- Department of Pathology, Beijing Ditan Hospital, Capital Medical University, Beijing, China
| | - Wei Sun
- Department of Cancer Center, Beijing Ditan Hospital, Capital Medical University, Beijing, China
| | - Lei Sun
- Department of Pathology, Beijing Ditan Hospital, Capital Medical University, Beijing, China
| | - Yanjun Shen
- Department of Cancer Center, Beijing Ditan Hospital, Capital Medical University, Beijing, China
| | - Ying Teng
- Department of Cancer Center, Beijing Ditan Hospital, Capital Medical University, Beijing, China
| | - Yawen Xu
- Department of Cancer Center, Beijing Ditan Hospital, Capital Medical University, Beijing, China
| | - Wendong Li
- Department of Cancer Center, Beijing Ditan Hospital, Capital Medical University, Beijing, China
| | - Mei Liu
- Department of Oncology, Beijing You'an Hospital, Capital Medical University, Beijing, China.
| | - Jinglong Chen
- Department of Cancer Center, Beijing Ditan Hospital, Capital Medical University, Beijing, China.
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Liu J, Xia S, Zhang B, Mohammed DM, Yang X, Zhu Y, Jiang X. Small molecule tyrosine kinase inhibitors approved for systemic therapy of advanced hepatocellular carcinoma: recent advances and future perspectives. Discov Oncol 2024; 15:259. [PMID: 38960980 PMCID: PMC11222362 DOI: 10.1007/s12672-024-01110-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/12/2024] [Accepted: 06/18/2024] [Indexed: 07/05/2024] Open
Abstract
Liver cancer is the sixth most commonly diagnosed cancer and the third leading cause of cancer death in the world, and hepatocellular carcinoma (HCC) is the most common form of liver cancer. More than half of the HCC patients are diagnosed at an advanced stage and often require systemic therapy. Dysregulation of the activity of receptor tyrosine kinases (RTKs) is involved in the development and progress of HCC, RTKs are therefore the potential targets for systemic therapy of advanced HCC (aHCC). Currently, a total of six small molecule tyrosine kinase inhibitors (TKIs) have been approved for aHCC, including first-line sorafenib, lenvatinib, and donafenib, and second-line regorafenib, cabozantinib, and apatinib. These TKIs improved patients survival, which are associated with disease stage, etiology, liver function, tumor burden, baseline levels of alpha-fetoprotein, and treatment history. This review focuses on the clinical outcomes of these TKIs in key clinical trials, retrospective and real-world studies and discusses the future perspectives of TKIs for aHCC, with an aim to provide up-to-date evidence for decision-making in the treatment of aHCC.
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Affiliation(s)
- Jianzhong Liu
- Clinical Laboratory, Wuhan No.7 Hospital, Zhong Nan 2nd Road, Wuhan, 430071, China
| | - Shuai Xia
- Department of Biochemistry and Molecular Biology, Jining Medical University, Jining, 272067, Shandong, China
| | - Baoyi Zhang
- National Engineering Research Center for Nanomedicine, Key Laboratory of Molecular Biophysics of the Ministry of Education, College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan, 430074, Hubei, China
| | - Dina Mostafa Mohammed
- Nutrition and Food Sciences Department, National Research Centre, Dokki, Cairo, Egypt
| | - Xiangliang Yang
- National Engineering Research Center for Nanomedicine, Key Laboratory of Molecular Biophysics of the Ministry of Education, College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan, 430074, Hubei, China
| | - Yanhong Zhu
- National Engineering Research Center for Nanomedicine, Key Laboratory of Molecular Biophysics of the Ministry of Education, College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan, 430074, Hubei, China
| | - Xinnong Jiang
- National Engineering Research Center for Nanomedicine, Key Laboratory of Molecular Biophysics of the Ministry of Education, College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan, 430074, Hubei, China.
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Hsiao YW, Sou FM, Wang JH, Chen YH, Tsai MC, Hu TH, Hung CH, Chen CH, Kuo YH. Well-controlled viremia reduces the progression of hepatocellular carcinoma in chronic viral hepatitis patients treated with lenvatinib. Kaohsiung J Med Sci 2023; 39:1233-1242. [PMID: 37843189 DOI: 10.1002/kjm2.12757] [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: 07/05/2023] [Revised: 08/12/2023] [Accepted: 08/28/2023] [Indexed: 10/17/2023] Open
Abstract
Lenvatinib has been approved as one of the first-line treatments for advanced hepatocellular carcinoma (HCC) due to its high treatment efficacy being non-inferior to sorafenib. Previous studies have shown well-controlled viremia contributes to the prognosis of HCC patients receiving first-line sorafenib; hence, we postulated this association might also exist in HCC patients with lenvatinib treatment. From April 2018 to December 2021, 201 unresectable HCC patients with first-line lenvatinib treatment in our institute were assessed. High-effect nucleoside analogues were administered for hepatitis B virus (HBV) control, while direct-acting antivirals were used for hepatitis C virus (HCV) elimination. Based on our previous study, well-controlled viremia was defined as patients who had undetectable viremia, or who had been receiving antivirals at least 6 months before lenvatinib. This study enrolled 129 patients, including 85 patients with HBV-related HCC (HBV-HCC) and 44 patients with HCV-related HCC (HCV-HCC), respectively. Progression-free survival (PFS) and overall survival (OS) rates between the two groups were not different. Before administration of lenvatinib, 57.1% of the HBV-HCC patients and 88.4% of the HCV-HCC patients had well-controlled viremia, and their PFS (8.8 vs. 3.1 months, p < 0.001) and OS (30.2 vs. 12.8 months, p = 0.041) were better than those who had uncontrolled viremia; moreover, well-controlled viremia reduced tumor progression in multivariate analysis (Hazard ratio: 0.41, 95% confidence interval: 0.25-0.68, p = 0.001) after adjusting for albumin-bilirubin grade and concurrent treatment. HBV or HCV infection was not associated with tumor progression of HCC patients receiving lenvatinib, but viremia, controlled or not, was.
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Affiliation(s)
- Ya-Wen Hsiao
- Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan
| | - Fai-Meng Sou
- Division of Hepatogastroenterology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan
| | - Jing-Houng Wang
- Division of Hepatogastroenterology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan
| | - Yen-Hao Chen
- Division of Hematology-Oncology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan
| | - Ming-Chao Tsai
- Division of Hepatogastroenterology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan
| | - Tsung-Hui Hu
- Division of Hepatogastroenterology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan
| | - Chao-Hung Hung
- Division of Hepatogastroenterology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan
| | - Chien-Hung Chen
- Division of Hepatogastroenterology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan
| | - Yuan-Hung Kuo
- Division of Hepatogastroenterology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan
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Lin LW, Yan LY, Ke K, Yang WZ, Lin JQ, Huang N. Efficacy and safety of transarterial chemoembolization combined with lenvatinib, programmed death-1 inhibitor, and iodine-125 seed brachytherapy for hepatocellular carcinoma with portal vein tumor thrombosis. Brachytherapy 2023; 22:858-871. [PMID: 37574351 DOI: 10.1016/j.brachy.2023.06.229] [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: 04/03/2023] [Revised: 06/28/2023] [Accepted: 06/28/2023] [Indexed: 08/15/2023]
Abstract
BACKGROUND Therapy for hepatocellular carcinoma (HCC) patients with portal vein tumor thrombosis (PVTT) is still controversial. This study was performed to evaluate the efficacy and safety of the combination therapy comprising transarterial chemoembolization (TACE), lenvatinib (L), programmed death-1 inhibitor (P), and iodine-125 seed (I125) brachytherapy relative to TACE in combination with lenvatinib plus programmed death-1 inhibitor therapy and TACE plus lenvatinib therapy. METHODS The data of HCC patients with PVTT from July 2017 to August 2022 were assessed in this single-center retrospective study. Primary study outcomes were progression-free survival (PFS) and overall survival (OS), while the secondary outcomes were disease control rate (DCR), objective response rate (ORR), and treatment-related adverse events. RESULTS We enrolled 150 patients totally, including 50 patients treated with TACE plus lenvatinib therapy (TACE+L group), 45 patients treated with TACE in combination with lenvatinib plus programmed death-1 inhibitor therapy (TACE+L+P group), and 55 patients treated with the combination therapy of TACE along with I125 brachytherapy, lenvatinib, and programmed death-1 inhibitor therapy (TACE+L+P+I125 group). The median OS in the TACE+L+P+I125 group (21.0; 95% confidence interval [CI]: 18.4∼23.5 months) was significantly longer than that in the TACE+L group (10; 95% CI: 7.8∼12.1months) (p = 0.006), while it was insignificantly longer than that in the TACE+L+P group (14.0; 95% CI: 10.7∼17.2months) (p = 0.058). The median PFS in the TACE+L+P+I125 group (13.0; 95% CI: 10.2∼15.7 months) was significantly longer than that in the TACE+L group (5.0; 95% CI: 4.2∼5.7 months) (p = 0.014) and the TACE+L+P group (9.0; 95% CI: 6.7∼11.2 months) (p = 0.048). Statistically significant differences between groups were found in DCR (p = 0.015). There were no significant between-group differences in treatment-related adverse events (p > 0.05). CONCLUSIONS A combination therapy of TACE, lenvatinib, programmed death-1 inhibitor, and I125 seed brachytherapy significantly improve OS, PFS, and DCR and show better survival prognosis for HCC patients accompanied by PVTT.
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Affiliation(s)
- Long-Wang Lin
- Department of Interventional Radiology, Fujian Medical University Union Hospital, Fuzhou, Fujian, China
| | - Le-Ye Yan
- Department of Interventional Radiology, Fujian Medical University Union Hospital, Fuzhou, Fujian, China
| | - Kun Ke
- Department of Interventional Radiology, Fujian Medical University Union Hospital, Fuzhou, Fujian, China
| | - Wei-Zhu Yang
- Department of Interventional Radiology, Fujian Medical University Union Hospital, Fuzhou, Fujian, China
| | - Jun-Qing Lin
- Department of Interventional Radiology, Fujian Medical University Union Hospital, Fuzhou, Fujian, China.
| | - Ning Huang
- Department of Interventional Radiology, Fujian Medical University Union Hospital, Fuzhou, Fujian, China.
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Lin LW, Ke K, Yan LY, Chen R, Huang JY. Efficacy and safety of hepatic artery infusion chemotherapy combined with tyrosine kinase inhibitors plus programmed death-1 inhibitors for hepatocellular carcinoma refractory to transarterial chemoembolization. Front Oncol 2023; 13:1178428. [PMID: 37207144 PMCID: PMC10189040 DOI: 10.3389/fonc.2023.1178428] [Citation(s) in RCA: 8] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/02/2023] [Accepted: 04/18/2023] [Indexed: 05/21/2023] Open
Abstract
Background The subsequent therapy for hepatocellular carcinoma (HCC) patients with refractory to transarterial chemoembolization (TACE) is still controversial. This study was performed to evaluate the efficacy and safety of combination therapy comprising hepatic artery infusion chemotherapy (HAIC), lenvatinib, and programmed death-1 inhibitors relative to HAIC combined with lenvatinib. Methods In this single-center retrospective study, we analyzed data from HCC patients with refractory to TACE from June 2017 to July 2022. Primary study outcomes were overall survival (OS) and progression-free survival (PFS), while the secondary outcomes were the objective response rate (ORR), disease control rate (DCR), and treatment-related adverse events. Results We enrolled 149 patients finally, including 75 patients who received HAIC combined with lenvatinib plus PD-1 inhibitors therapy (HAIC+L+P group) and 74 patients who received HAIC combined with lenvatinib therapy (HAIC+L group). The median OS in the HAIC+L+P group (16.0; 95% CI: 13.6~18.3 months) was significantly higher compared to the HAIC+L group (9.0; 95% CI: 6.5~11.4 months) (p = 0.002), while the median PFS in the HAIC+L+P group (11.0; 95% CI: 8.6~13.3 months) was significantly higher compared to the HAIC+L group (6.0; 95% CI: 5.0~6.9 months) (p < 0.001). Significant between-group differences in DCR (p = 0.027) were found. Additionally, 48 pairs of patients were matched after propensity matching analysis. The survival prognosis between two groups before propensity matching is similar to that after propensity matching. Moreover, the percentage of patients with hypertension in the HAIC+L+P group was significantly higher compared to the HAIC+L group (28.00% vs. 13.51%; p = 0.029). Conclusions A combination therapy of HAIC, lenvatinib, and programmed death-1 inhibitors significantly improved oncologic response and prolonged survival duration, showing a better survival prognosis for HCC patients with refractory toTACE.
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Persano M, Casadei-Gardini A, Burgio V, Scartozzi M, Cascinu S, Rimini M. Five years of lenvatinib in hepatocellular carcinoma: are there any predictive and/or prognostic factors? Expert Rev Anticancer Ther 2023; 23:19-27. [PMID: 36472371 DOI: 10.1080/14737140.2023.2156340] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
INTRODUCTION Lenvatinib was the first drug approved in 2017 for first-line treatment of hepatocarcinoma (HCC) after 10 years of Sorafenib as exclusive standard of care. The therapeutic armamentarium has recently expanded following the approval of atezolizumab plus bevacizumab. AREAS COVERED Numerous studies have been conducted during the past 5 years on Lenvatinib use in real-world settings in an effort to determine prognostic and predictive factors of Lenvatinib efficacy. In order to choose the most effective therapeutic approach, it may be helpful to summarize these results in this review. EXPERT OPINION A subgroup that appears to benefit most from Lenvatinib therapy are patients with non-viral cirrhosis. This aspect is of great importance today considering the increase in NASH prevalence. Also, a significant proportion of BCLC B patients appear to respond well to Lenvatinib therapy. The biological heterogeneity highlighted in HCC patients, along with the growing number of therapeutic options, makes the identification of stratification tools able to define which patients are more likely to respond to a treatment rather than another one of crucial interest. Further investigation deepening the biological pathways underlying HCC carcinogenesis are of particular interest in order to pave the way for precision medicine even for HCC patients.
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Affiliation(s)
- Mara Persano
- Medical Oncology, University Hospital of Cagliari, Milan, Italy
| | - Andrea Casadei-Gardini
- Department of Oncology, Vita-Salute San Raffaele University, IRCCS San Raffaele Scientific Institute Hospital, Milan, Italy
| | - Valentina Burgio
- IRCCS San Raffaele Scientific Institute Hospital, Department of Oncology, Vita-Salute San Raffaele University, Milan, Italy
| | - Mario Scartozzi
- Medical Oncology, University Hospital of Cagliari, Milan, Italy
| | - Stefano Cascinu
- Department of Oncology, Vita-Salute San Raffaele University, IRCCS San Raffaele Scientific Institute Hospital, Milan, Italy
| | - Margherita Rimini
- IRCCS San Raffaele Scientific Institute Hospital, Department of Oncology, Vita-Salute San Raffaele University, Milan, Italy
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Su C, Teng W, Lin P, Jeng W, Chen K, Hsieh Y, Chen W, Ho M, Hsieh C, Wang C, Chai P, Lin C, Lin C, Lin S. Similar efficacy and safety between lenvatinib versus atezolizumab plus bevacizumab as the first‐line treatment for unresectable hepatocellular carcinoma. Cancer Med 2022; 12:7077-7089. [PMID: 36468578 PMCID: PMC10067067 DOI: 10.1002/cam4.5506] [Citation(s) in RCA: 17] [Impact Index Per Article: 5.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/13/2022] [Revised: 10/06/2022] [Accepted: 11/19/2022] [Indexed: 12/07/2022] Open
Abstract
BACKGROUND Lenvatinib and atezolizumab plus bevacizumab(A + B) have been used for unresectable hepatocellular carcinoma (HCC) as first-line therapy. Real-world studies comparison of efficacy and safety in these two regimens are limited, we therefore conduct this study to investigate these issues. METHODS We retrospectively reviewed patients received lenvatinib (n = 46) and A + B (n = 46) as first-line systemic therapy for unresectable HCC in a tertiary medical center. Objective response rate (ORR), progression free survival (PFS), and overall survival (OS) were evaluated according to modified Response Evaluation Criteria in Solid Tumors (mRECIST). Inverse probability weighting (IPW) was performed for baseline clinical features balance. RESULTS A total of 92 patients with median age of 63.8 year-old, 78.3% male, 85.9% viral hepatitis infected, 67.4% BCLC stage C were enrolled. The median treatment and follow-up duration were 4.7 months and 9.4 months, respectively. There was no significant difference in ORR (26.1% vs. 41.3%, p = 0.1226), PFS (5.9 vs. 5.3 months, p = 0.4066), and OS (not reached vs. not reached, p = 0.7128) between the lenvatinib and A + B groups. After IPW, the results of survival and response rate were also compared. Subgroup analysis suggested that using lenvatinib was not inferior to A + B in regards of PFS, including those with elder, Child-Pugh class B, beyond up-to-seven, or portal vein invasion VP4 patients. Among the lenvatinib treated patients, multivariate analysis showed patients elder than 65-year-old was an independent predictor associated with shorter PFS (adjust HR: 2.085[0.914-4.753], p = 0.0213). The incidence rates of adverse events were similar between two groups (76 vs. 63%, p = 0.1740). Both of two regimens had similarly few impact on liver function by comparison of baseline, third month, and sixth month albumin-bilirubin index and Child-Pugh score. CONCLUSIONS The efficacy and safety of lenvatinib are similar to A + B as a first-line systemic therapy for unresectable HCC.
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Affiliation(s)
- Chung‐Wei Su
- Department of Gastroenterology and Hepatology Chang Gung Memorial Hospital, Linkou Medical Center Taoyuan Taiwan
- College of Medicine, Chang Gung University Taoyuan Taiwan
| | - Wei Teng
- Department of Gastroenterology and Hepatology Chang Gung Memorial Hospital, Linkou Medical Center Taoyuan Taiwan
- College of Medicine, Chang Gung University Taoyuan Taiwan
| | - Po‐Ting Lin
- Department of Gastroenterology and Hepatology Chang Gung Memorial Hospital, Linkou Medical Center Taoyuan Taiwan
- College of Medicine, Chang Gung University Taoyuan Taiwan
| | - Wen‐Juei Jeng
- Department of Gastroenterology and Hepatology Chang Gung Memorial Hospital, Linkou Medical Center Taoyuan Taiwan
- College of Medicine, Chang Gung University Taoyuan Taiwan
| | - Kuei‐An Chen
- College of Medicine, Chang Gung University Taoyuan Taiwan
- Department of Medical Imaging and Intervention Chang Gung Memorial Hospital, Linkou Medical Center Taoyuan Taiwan
| | - Yi‐Chung Hsieh
- Department of Gastroenterology and Hepatology Chang Gung Memorial Hospital, Linkou Medical Center Taoyuan Taiwan
- College of Medicine, Chang Gung University Taoyuan Taiwan
| | - Wei‐Ting Chen
- Department of Gastroenterology and Hepatology Chang Gung Memorial Hospital, Linkou Medical Center Taoyuan Taiwan
- College of Medicine, Chang Gung University Taoyuan Taiwan
| | - Ming‐Mo Ho
- College of Medicine, Chang Gung University Taoyuan Taiwan
- Department of Medical Oncology Chang Gung Memorial Hospital, Linkou Medical Center Taoyuan Taiwan
| | - Chia‐Hsun Hsieh
- College of Medicine, Chang Gung University Taoyuan Taiwan
- Department of Medical Oncology Tucheng Composite Municipal Hospital New Taipei Taiwan
| | - Ching‐Ting Wang
- College of Medicine, Chang Gung University Taoyuan Taiwan
- Department of Nursing Chang Gung Memorial Hospital, Linkou Medical Center Taoyuan Taiwan
| | - Pei‐Mei Chai
- College of Medicine, Chang Gung University Taoyuan Taiwan
- Department of Nursing Chang Gung Memorial Hospital, Linkou Medical Center Taoyuan Taiwan
| | - Chen‐Chun Lin
- Department of Gastroenterology and Hepatology Chang Gung Memorial Hospital, Linkou Medical Center Taoyuan Taiwan
- College of Medicine, Chang Gung University Taoyuan Taiwan
| | - Chun‐Yen Lin
- Department of Gastroenterology and Hepatology Chang Gung Memorial Hospital, Linkou Medical Center Taoyuan Taiwan
- College of Medicine, Chang Gung University Taoyuan Taiwan
| | - Shi‐Ming Lin
- Department of Gastroenterology and Hepatology Chang Gung Memorial Hospital, Linkou Medical Center Taoyuan Taiwan
- College of Medicine, Chang Gung University Taoyuan Taiwan
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Casadei-Gardini A, Rimini M, Kudo M, Shimose S, Tada T, Suda G, Goh MJ, Jefremow A, Scartozzi M, Cabibbo G, Campani C, Tamburini E, Tovoli F, Ueshima K, Aoki T, Iwamoto H, Torimura T, Kumada T, Hiraoka A, Atsukawa M, Itobayashi E, Toyoda H, Sakamoto N, Sho T, Kang W, Siebler J, Neurath MF, Burgio V, Cascinu S. Real Life Study of Lenvatinib Therapy for Hepatocellular Carcinoma: RELEVANT Study. Liver Cancer 2022; 11:527-539. [PMID: 36589723 PMCID: PMC9801178 DOI: 10.1159/000525145] [Citation(s) in RCA: 22] [Impact Index Per Article: 7.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/27/2021] [Accepted: 05/11/2022] [Indexed: 02/04/2023] Open
Abstract
INTRODUCTION In the REFLECT trial, lenvatinib was found to be noninferior compared to sorafenib in terms of overall survival. Here, we analyze the effects of lenvatinib in the real-life experience of several centers across the world and identify clinical factors that could be significantly associated with survival outcomes. METHODS The study population was derived from retrospectively collected data of HCC patients treated with lenvatinib. The overall cohort included western and eastern populations from 23 center in five countries. RESULTS We included 1,325 patients with HCC and treated with lenvatinib in our analysis. Median OS was 16.1 months. Overall response rate was 38.5%. Multivariate analysis for OS highlighted that HBsAg positive, NLR >3, and AST >38 were independently associated with poor prognosis in all models. Conversely, NAFLD/NASH-related etiology was independently associated with good prognosis. Median progression-free survival was 6.3 months. Multivariate analysis for progression-free survival revealed that NAFLD/NASH, BCLC, NLR, and AST were independent prognostic factors for progression-free survival. A proportion of 75.2% of patients suffered from at least one adverse effect during the study period. Multivariate analysis exhibited the appearance of decreased appetite grade ≥2 versus grade 0-1 as an independent prognostic factor for worse progression-free survival. 924 patients of 1,325 progressed during lenvatinib (69.7%), and 827 of them had a follow-up over 2 months from the beginning of second-line treatment. From first-line therapy, the longest median OS was obtained with the sequence lenvatinib and immunotherapy (47.0 months), followed by TACE (24.7 months), ramucirumab (21.2 months), sorafenib (15.7 months), regorafenib (12.7 months), and best supportive care (10.8 months). CONCLUSIONS Our study confirms in a large and global population of patients with advanced HCC, not candidates for locoregional treatment the OS reported in the registration study and a high response rate with lenvatinib.
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Affiliation(s)
- Andrea Casadei-Gardini
- Department of Oncology, Vita-Salute San Raffaele University, IRCCS San Raffaele Scientific Institute Hospital, Milan, Italy
- Department of Medical Oncology, San Raffaele Scientific Institute IRCCS, Milan, Italy
| | - Margherita Rimini
- Division of Oncology, Department of Oncology and Hematology, University Hospital of Modena, Modena, Italy
| | - Masatoshi Kudo
- Department of Gastroenterology and Hepatology, Kindai University Faculty of Medicine, Osaka, Japan
| | - Shigeo Shimose
- Division of Gastroenterology, Department of Medicine, Kurume University School of Medicine, Kurume, Japan
| | - Toshifumi Tada
- Department of Internal Medicine, Japanese Red Cross Himeji Hospital, Himeji, Japan
| | - Goki Suda
- Department of Gastroenterology and Hepatology, Hokkaido, University Graduate School of Medicine, Sapporo, Japan
| | - Myung Ji Goh
- Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea
| | - Andre Jefremow
- Department of Medicine 1, University Hospital Erlangen, Friedrich-Alexander-Universitaet Erlangen-Nuremberg, Erlangen, Germany
- Deutsches Zentrum Immuntherapie, Erlangen, Germany
| | - Mario Scartozzi
- Medical Oncology Unit, University Hospital and University of Cagliari, Cagliari, Italy
| | - Giuseppe Cabibbo
- Section of Gastroenterology & Hepatology, Department of Health Promotion Sciences Maternal and Infant Care, Internal Medicine and Medical Specialties, PROMISE, University of Palermo, Palermo, Italy
| | - Claudia Campani
- Department of Experimental and Clinical Medicine, University of Florence, Florence, Italy
| | - Emiliano Tamburini
- Department of Oncology and Palliative Care, Cardinale G Panico, Tricase City Hospital, Tricase, Italy
| | - Francesco Tovoli
- Division of Internal Medicine, Hepatobiliary and Immunoallergic Diseases, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy
| | - Kazuomi Ueshima
- Department of Gastroenterology and Hepatology, Kindai University Faculty of Medicine, Osaka, Japan
| | - Tomoko Aoki
- Department of Gastroenterology and Hepatology, Kindai University Faculty of Medicine, Osaka, Japan
| | - Hideki Iwamoto
- Division of Gastroenterology, Department of Medicine, Kurume University School of Medicine, Kurume, Japan
| | - Takuji Torimura
- Division of Gastroenterology, Department of Medicine, Kurume University School of Medicine, Kurume, Japan
| | - Takashi Kumada
- Department of Medical Oncology, San Raffaele Scientific Institute IRCCS, Milan, Italy
| | - Atsushi Hiraoka
- Gastroenterology Center, Ehime Prefectural Central Hospital, Matsuyama, Japan
| | - Masanori Atsukawa
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Nippon Medical School, Tokyo, Japan
| | - Ei Itobayashi
- Department of Gastroenterology, Asahi General Hospital, Asahi, Japan
| | - Hidenori Toyoda
- Department of Gastroenterology and Hepatology, Ogaki Municipal Hospital, Ogaki, Japan
| | - Naoya Sakamoto
- Department of Gastroenterology and Hepatology, Hokkaido, University Graduate School of Medicine, Sapporo, Japan
| | - Takuya Sho
- Department of Gastroenterology and Hepatology, Hokkaido, University Graduate School of Medicine, Sapporo, Japan
| | - Wonseok Kang
- Department of Health Sciences and Technology, Samsung Advanced Institute for Health Sciences and Technology (SAIHST), Sungkyunkwan University, Seoul, Republic of Korea
| | - Jürgen Siebler
- Department of Medicine 1, University Hospital Erlangen, Friedrich-Alexander-Universitaet Erlangen-Nuremberg, Erlangen, Germany
- Deutsches Zentrum Immuntherapie, Erlangen, Germany
| | - Markus Friedrich Neurath
- Department of Medicine 1, University Hospital Erlangen, Friedrich-Alexander-Universitaet Erlangen-Nuremberg, Erlangen, Germany
- Deutsches Zentrum Immuntherapie, Erlangen, Germany
| | - Valentina Burgio
- Department of Medical Oncology, San Raffaele Scientific Institute IRCCS, Milan, Italy
| | - Stefano Cascinu
- Department of Oncology, Vita-Salute San Raffaele University, IRCCS San Raffaele Scientific Institute Hospital, Milan, Italy
- Department of Medical Oncology, San Raffaele Scientific Institute IRCCS, Milan, Italy
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9
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Sun B, Zhang L, Sun T, Ren Y, Cao Y, Zhang W, Zhu L, Guo Y, Gui Y, Liu F, Chen L, Xiong F, Zheng C. Safety and efficacy of lenvatinib combined with camrelizumab plus transcatheter arterial chemoembolization for unresectable hepatocellular carcinoma: A two-center retrospective study. Front Oncol 2022; 12:982948. [PMID: 36172158 PMCID: PMC9511022 DOI: 10.3389/fonc.2022.982948] [Citation(s) in RCA: 22] [Impact Index Per Article: 7.3] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/30/2022] [Accepted: 08/17/2022] [Indexed: 12/03/2022] Open
Abstract
Objectives To compare the safety and efficacy of lenvatinib (LEN) combined with camrelizumab plus transcatheter arterial chemoembolization (TACE-LEN-C) and TACE combined with LEN (TACE-LEN) in patients with unresectable hepatocellular carcinoma (uHCC). Methods Eighty-three patients with uHCC treated with TACE-LEN-C or TACE-LEN from September 2018 to May 2021 were enrolled in this retrospective study. Overall survival (OS), progression-free survival (PFS), local tumor response, and adverse events (AEs) were evaluated. Univariate and multivariate analyses were used to determine the factors affecting survival. Results There were 31 patients in the TACE-LEN-C group and 52 patients in the TACE-LEN group. The median follow-up period was 14.2 months (range 7.2–25.2 months) in the whole study. The combination of triple therapy was found to significantly prolong the PFS (12.5 months vs. 6.6 months, P<0.001) and OS (18.9 months vs. 13.9 months, P<0.001. In terms of tumor response, the combination demonstrated a higher objective response rate (71% vs. 42.3% by the modified Response Evaluation Criteria in Solid Tumors, P=0.023) without a statistically significant difference in the disease control rate (93.5% in TACE-LEN-C, 80.8% in TACE-LEN, P=0.195). In the multivariate analysis, two independent factors affecting PFS were identified: number of tumors and treatment. Three independent factors affected OS: number of tumors, Barcelona Clinic Liver Cancer (BCLC) stage, and treatment. All the AEs were tolerable. Conclusion TACE-LEN-C is a safe and effective treatment for patients with uHCC, and could be a potential treatment option.
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Affiliation(s)
- Bo Sun
- Department of Radiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
- Key Laboratory of Molecular Imaging of Hubei Province, Wuhan, China
- Department of Interventional Radiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Lijie Zhang
- Department of Radiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
- Key Laboratory of Molecular Imaging of Hubei Province, Wuhan, China
- Department of Interventional Radiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Tao Sun
- Department of Radiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
- Key Laboratory of Molecular Imaging of Hubei Province, Wuhan, China
- Department of Interventional Radiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Yanqiao Ren
- Department of Radiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
- Key Laboratory of Molecular Imaging of Hubei Province, Wuhan, China
- Department of Interventional Radiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Yanyan Cao
- Department of Radiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
- Key Laboratory of Molecular Imaging of Hubei Province, Wuhan, China
- Department of Interventional Radiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Weihua Zhang
- Department of Radiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
- Key Laboratory of Molecular Imaging of Hubei Province, Wuhan, China
- Department of Interventional Radiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Licheng Zhu
- Department of Radiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
- Key Laboratory of Molecular Imaging of Hubei Province, Wuhan, China
- Department of Interventional Radiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Yusheng Guo
- Department of Radiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
- Key Laboratory of Molecular Imaging of Hubei Province, Wuhan, China
- Department of Interventional Radiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Yuxi Gui
- Department of Radiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
- Key Laboratory of Molecular Imaging of Hubei Province, Wuhan, China
- Department of Interventional Radiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Fengyong Liu
- Department of Interventional Radiology, The Fifth Medical Center of Chinese, People’s Liberation Army (PLA) General Hospital, Beijing, China
| | - Lei Chen
- Department of Radiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
- Key Laboratory of Molecular Imaging of Hubei Province, Wuhan, China
- Department of Interventional Radiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
- *Correspondence: Chuansheng Zheng, ; Fu Xiong, ; Lei Chen,
| | - Fu Xiong
- Department of Radiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
- Key Laboratory of Molecular Imaging of Hubei Province, Wuhan, China
- Department of Interventional Radiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
- *Correspondence: Chuansheng Zheng, ; Fu Xiong, ; Lei Chen,
| | - Chuansheng Zheng
- Department of Radiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
- Key Laboratory of Molecular Imaging of Hubei Province, Wuhan, China
- Department of Interventional Radiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
- *Correspondence: Chuansheng Zheng, ; Fu Xiong, ; Lei Chen,
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10
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Immune-Related lncRNAs with WGCNA Identified the Function of SNHG10 in HBV-Related Hepatocellular Carcinoma. JOURNAL OF ONCOLOGY 2022; 2022:9332844. [PMID: 35847362 PMCID: PMC9279027 DOI: 10.1155/2022/9332844] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 03/18/2022] [Revised: 05/14/2022] [Accepted: 05/17/2022] [Indexed: 11/18/2022]
Abstract
Objective. The hepatitis B virus (HBV) infection led to hepatitis, which was one of common reasons for hepatocellular carcinoma (HCC). The immune microenvironment alteration played a crucial role in this process. The study aimed to identify immune-related long noncoding RNAs (lncRNAs) in HBV-related HCC and explore potential mechanisms. Methods. In total, 1,072 immune‐related genes (IRGs) were enriched in different co-expression modules with weighted gene co-expression network analysis (WGCNA) combining the corresponding clinical features in HBV-related HCC. The immune-related lncRNAs were selected from the crucial co-expression model based on the correlation analysis with IRGs. The immune-related lncRNAs were furtherly used to construct prognostic signature by the Cox proportional hazards regression and Lasso regression. Furthermore, the proliferation and migration ability of lncRNA SNHG10 were verified in vitro. Results. A total of nine co-expression modules were identified by WGCNA of which the “red” co-expression module was most correlated with various clinical characteristics. Additionally, the IRGs in this module were significantly enriched in multiple immune-related pathways. The twelve immune-related lncRNAs prognostic signature (HAND2-AS1, LINC00844, SNHG10, MALAT1, LINC00460, LBX2-AS1, MIR31HG, SEMA6A-AS1, LINC1278, LINC00514, CTBP-AS2, and LINC00205) was constructed. The risk score was an independent risk factor in HBV-related HCC and verified by principal components analysis (PCA), nomogram, and PCR between different cell lines. Moreover, the proportion of immune cells were significantly different between high-risk score group and low-risk score group. The malignant behavior of Hep3B was significantly different between si-lncRNA SNHG10 and control group. Conclusions. The immune-related lncRNAs prognostic signature provided some potential biomarkers and molecular mechanisms in HBV-related HCC.
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11
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Burgio V, Iavarone M, Di Costanzo GG, Marra F, Lonardi S, Tamburini E, Piscaglia F, Masi G, Celsa C, Foschi FG, Silletta M, Amoruso DC, Rimini M, Bruccoleri M, Tortora R, Campani C, Soldà C, Viola MG, Forgione A, Conti F, Salani F, Catanese S, Giacchetto CM, Fulgenzi C, Coppola C, Lampertico P, Pellino A, Rancatore G, Cabibbo G, Ratti F, Pedica F, Della Corte A, Colombo M, De Cobelli F, Aldrighetti L, Cascinu S, Casadei-Gardini A. Real-Life Clinical Data of Lenvatinib versus Sorafenib for Unresectable Hepatocellular Carcinoma in Italy. Cancer Manag Res 2022; 13:9379-9389. [PMID: 34992463 PMCID: PMC8713715 DOI: 10.2147/cmar.s330195] [Citation(s) in RCA: 31] [Impact Index Per Article: 10.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/26/2021] [Accepted: 10/05/2021] [Indexed: 12/24/2022] Open
Abstract
Background Lenvatinib has been approved in Italy since October 2019 as a first-line therapy for advanced hepatocellular carcinoma (HCC) and to date data on effectiveness and safety of lenvatinib are not available in our region. To fill this gap, we performed a multicentric analysis of the real-world treatment outcomes with the propensity score matching in a cohort of Italian patients with unresectable HCC who were treated with either sorafenib or lenvatinib. Aims and Methods To evaluate the effectiveness of sorafenib and lenvatinib as primary treatment of advanced HCC in clinical practice we performed a multicentric analysis of the treatment outcomes of 288 such patients recruited in 11 centers in Italy. A propensity score was used to mitigate confounding due to referral biases in the assessment of mortality and progression-free survival. Results Over a follow-up period of 11 months the Cox regression model showed 48% reduction of death risk for patients treated with lenvatinib (95% CI: 0.34-0.81; p = 0.0034), compared with those treated with sorafenib. The median PFS was 9.0 and 4.9 months for lenvatinib and sorafenib arm, respectively. Patients treated with lenvatinib showed a higher percentage of response rate (29.4% vs 2.8%; p < 0.00001) compared with patients treated with sorafenib. Sorafenib was shown to be correlated with more HFSR, diarrhea and fatigue, while lenvatinib with more hypertension and fatigue. Conclusion Our study highlighted for the first time the efficacy and safety of lenvatinib in an Italian cohort of patients.
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Affiliation(s)
- Valentina Burgio
- Department of Medical Oncology, Vita-Salute San Raffaele University, IRCCS San Raffaele Scientific Institute, Milan, 20132, Italy
| | - Massimo Iavarone
- Foundation IRCCS Ca' Granda Ospedale Maggiore Policlinico, Division of Gastroenterology and Hepatology, Milan, Italy
| | | | - Fabio Marra
- Dipartimento di Medicina Sperimentale e Clinica, Università di Firenze, Firenze, Italy
| | - Sara Lonardi
- Early Phase Clinical Trial Unit, Department of Oncology, Veneto Institute of Oncology IOV-IRCCS, Padua, Italy.,Medical Oncology Unit 1, Department of Oncology, Veneto Institute of Oncology IOV - IRCCS, Padua, Italy
| | - Emiliano Tamburini
- Department of Oncology and Palliative Care, Cardinale Hospital, Naples, Italy
| | - Fabio Piscaglia
- Division of Internal Medicine, Hepatobiliary and Immunoallergic Disease, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy
| | - Gianluca Masi
- Department of Translational Research and New Technologies in Medicine and Surgery, University of Pisa, Pisa, Italy.,Unit of Medical Oncology 2, Azienda Ospedaliero-Universitaria Pisana, Pisa, Italy
| | - Ciro Celsa
- Department of Surgical, Oncological and Oral Sciences (Di.Chir.On.S.), University of Palermo, Palermo, 90127, Italy
| | | | | | | | - Margherita Rimini
- Department of Oncology and Hematology, Division of Oncology, University of Modena and Reggio Emilia, Modena, 4121, Italy
| | - Mariangela Bruccoleri
- Foundation IRCCS Ca' Granda Ospedale Maggiore Policlinico, Division of Gastroenterology and Hepatology, Milan, Italy
| | | | - Claudia Campani
- Dipartimento di Medicina Sperimentale e Clinica, Università di Firenze, Firenze, Italy
| | - Caterina Soldà
- Medical Oncology Unit 1, Department of Oncology, Veneto Institute of Oncology IOV - IRCCS, Padua, Italy
| | | | - Antonella Forgione
- Division of Internal Medicine, Hepatobiliary and Immunoallergic Disease, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy
| | - Fabio Conti
- Internal Medicine, Infermi Hospital, Faenza (AUSL ROMAGNA), Ravenna, Italy
| | - Francesca Salani
- Department of Translational Research and New Technologies in Medicine and Surgery, University of Pisa, Pisa, Italy.,Unit of Medical Oncology 2, Azienda Ospedaliero-Universitaria Pisana, Pisa, Italy
| | - Silvia Catanese
- Department of Translational Research and New Technologies in Medicine and Surgery, University of Pisa, Pisa, Italy.,Unit of Medical Oncology 2, Azienda Ospedaliero-Universitaria Pisana, Pisa, Italy
| | - Carmelo Marco Giacchetto
- Section of Gastroenterology & Hepatology, Department of Health Promotion, Mother and Child Care, Internal Medicine and Medical Specialties, PROMISE, University of Palermo, Palermo, 90127, Italy
| | | | - Carmine Coppola
- Hepatology Unit, Internal Medicine, Area Stabiese Hospital, Naples, Italy
| | - Pietro Lampertico
- Liver Center, IRCCS San Raffaele Scientific Institute, Milan, 20132, Italy
| | - Antonio Pellino
- Medical Oncology Unit 1, Department of Oncology, Veneto Institute of Oncology IOV - IRCCS, Padua, Italy.,Department of Surgery, Oncology and Gastroenterology, University of Padua, Padua, Italy
| | - Gabriele Rancatore
- Section of Gastroenterology & Hepatology, Department of Health Promotion, Mother and Child Care, Internal Medicine and Medical Specialties, PROMISE, University of Palermo, Palermo, 90127, Italy
| | - Giuseppe Cabibbo
- Section of Gastroenterology & Hepatology, Department of Health Promotion, Mother and Child Care, Internal Medicine and Medical Specialties, PROMISE, University of Palermo, Palermo, 90127, Italy
| | - Francesca Ratti
- Hepatobiliary Surgery Division, Liver Center, Vita-Salute San Raffaele University, IRCCS San Raffaele Scientific Institute, Milan, 20132, Italy
| | - Federica Pedica
- Department of Experimental Oncology, Pathology Unit, IRCCS San Raffaele Scientific Institute, Milan, 20132, Italy
| | - Angelo Della Corte
- Department of Radiology, Vita-Salute San Raffaele University, IRCCS San Raffaele Scientific Institute, Milan, 20132, Italy
| | - Massimo Colombo
- Liver Center, IRCCS San Raffaele Scientific Institute, Milan, 20132, Italy
| | | | - Luca Aldrighetti
- Hepatobiliary Surgery Division, Liver Center, Vita-Salute San Raffaele University, IRCCS San Raffaele Scientific Institute, Milan, 20132, Italy
| | - Stefano Cascinu
- Department of Medical Oncology, Vita-Salute San Raffaele University, IRCCS San Raffaele Scientific Institute, Milan, 20132, Italy.,School of Medicine, Vita-Salute San Raffaele University, Milan, 20132, Italy
| | - Andrea Casadei-Gardini
- Department of Medical Oncology, Vita-Salute San Raffaele University, IRCCS San Raffaele Scientific Institute, Milan, 20132, Italy.,School of Medicine, Vita-Salute San Raffaele University, Milan, 20132, Italy
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12
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Rimini M, Shimose S, Lonardi S, Tada T, Masi G, Iwamoto H, Lai E, Burgio V, Hiraoka A, Ishikawa T, Soldà C, Shirono T, Vivaldi C, Takaguchi K, Shimada N, Astara G, Koga H, Nouso K, Joko K, Torimura T, Hiasa Y, Salani F, Scartozzi M, Cascinu S, Casadei-Gardini A. Lenvatinib versus Sorafenib as first-line treatment in hepatocellular carcinoma: A multi-institutional matched case-control study. Hepatol Res 2021; 51:1229-1241. [PMID: 34591334 DOI: 10.1111/hepr.13718] [Citation(s) in RCA: 31] [Impact Index Per Article: 7.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/18/2021] [Revised: 09/16/2021] [Accepted: 09/23/2021] [Indexed: 12/24/2022]
Abstract
BACKGROUND Advanced Hepatocarcinoma (HCC) is an important health problem worldwide. Recently, the REFLECT trial demonstrated the non-inferiority of Lenvatinib compared to Sorafenib in I line setting, thus leading to the approval of new first-line standard of care, along with Sorafenib. AIMS AND METHODS With aim to evaluate the optimal choice between Sorafenib and Lenvatinib as primary treatment in clinical practice, we performed a multicentric analysis with the propensity score matching on 184 HCC patients. RESULTS The median overall survival (OS) were 15.2 and 10.5 months for Lenvatinib and Sorafenib arm, respectively. The median progression-free survival (PFS) was 7.0 and 4.5 months for Lenvatinib and Sorafenib arm, respectively. Patients treated with Lenvatinib showed a 36% reduction of death risk (p = 0.0156), a 29% reduction of progression risk (p = 0.0446), a higher response rate (p < 0.00001) and a higher disease control rate (p = 0.002). Sorafenib showed to be correlated with more hand-foot skin reaction and Lenvatinib with more hypertension and fatigue. We highlighted the prognostic role of Barcelona Clinic Liver Cancer (BCLC) stage, Eastern Cooperative Oncology Group Performance Status (ECOG-PS), bilirubin, alkaline phosphatase and eosinophils for Sorafenib. Conversely, albumin, aspartate aminotransferase (AST), alkaline phosphatase and Neutrophil-Lymphocyte Ratio (NLR) resulted prognostic in Lenvatinib arm. Finally, we highlighted the positive predictive role of albumin > Normal Value (NV), ECOG > 0, NLR < 3, absence of Hepatitis C Virus positivity, and presence of portal vein thrombosis in favor of Lenvatinib arm. Eosinophil < 50 and ECOG > 0 negatively predicted the response to Sorafenib. CONCLUSION SLenvatinib showed to better perform in a real-word setting compared to Sorafenib. More researches are needed to validate the predictor factors of response to Lenvatinib rather than Sorafenib.
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Affiliation(s)
- Margherita Rimini
- Division of Oncology, Department of Oncology and Hematology, University of Modena and Reggio Emilia, Modena, Italy
| | - Shigeo Shimose
- Division of Gastroenterology, Department of Medicine, Kurume University School of Medicine, Kurume, Japan
| | - Sara Lonardi
- Early Phase Clinical Trial Unit, Department of Oncology, Veneto Institute of Oncology IOV-IRCCS, Padua, Italy
- Medical Oncology Unit 1, Department of Oncology, Veneto Institute of Oncology IOV-IRCCS, Padua, Italy
| | - Toshifumi Tada
- Department of Internal Medicine, Japanese Red Cross Himeji Hospital, Himeji, Japan
| | - Gianluca Masi
- Unit of Medical Oncology, Pisa University Hospital, Pisa, Italy
| | - Hideki Iwamoto
- Division of Gastroenterology, Department of Medicine, Kurume University School of Medicine, Kurume, Japan
| | - Eleonora Lai
- Medical Oncology Unit, University Hospital and University of Cagliari, Cagliari, Italy
| | - Valentina Burgio
- Department of Medical Oncology, IRCCS San Raffaele Hospital, Milan, Italy
| | - Atsushi Hiraoka
- Gastroenterology Center, Ehime Prefectural Central Hospital, Matsuyama, Japan
| | - Toru Ishikawa
- Department of Gastroenterology, Saiseikai Niigata Hospital, Niigata, Japan
| | - Caterina Soldà
- Medical Oncology Unit 1, Department of Oncology, Veneto Institute of Oncology IOV-IRCCS, Padua, Italy
| | - Tomotake Shirono
- Division of Gastroenterology, Department of Medicine, Kurume University School of Medicine, Kurume, Japan
| | | | - Koichi Takaguchi
- Department of Hepatology, Kagawa Prefectural Central Hospital, Takamatsu, Japan
| | - Noritomo Shimada
- Division of Gastroenterology and Hepatology, Otakanomori Hospital, Kashiwa, Japan
| | - Giorgio Astara
- Medical Oncology Unit, University Hospital and University of Cagliari, Cagliari, Italy
| | - Hironori Koga
- Division of Gastroenterology, Department of Medicine, Kurume University School of Medicine, Kurume, Japan
| | - Kazuhiro Nouso
- Department of Gastroenterology, Okayama City Hospital, Okayama, Japan
| | - Kouji Joko
- Hepato-biliary Center, Matsuyama Red Cross Hospital, Matsuyama, Japan
| | - Takuji Torimura
- Division of Gastroenterology, Department of Medicine, Kurume University School of Medicine, Kurume, Japan
| | - Yoichi Hiasa
- Department of Gastroenterology and Metabology, Ehime University Graduate School of Medicine, Matsuyama, Japan
| | | | - Mario Scartozzi
- Medical Oncology Unit, University Hospital and University of Cagliari, Cagliari, Italy
| | - Stefano Cascinu
- Department of Medical Oncology, IRCCS San Raffaele Hospital, Milan, Italy
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13
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Sally R, Ugonabo N, Nguyen A, Kim RH, Lo Sicco K. Lenvatinib-induced psoriasiform eruption and palmoplantar erythema in a patient with hepatocellular carcinoma. JAAD Case Rep 2021; 15:1-3. [PMID: 34381857 PMCID: PMC8340048 DOI: 10.1016/j.jdcr.2021.07.001] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/17/2022] Open
Affiliation(s)
- Rachel Sally
- Ronald O. Perelman Department of Dermatology, New York University Grossman School of Medicine, New York, New York
| | - Nkemjika Ugonabo
- Ronald O. Perelman Department of Dermatology, New York University Grossman School of Medicine, New York, New York
| | - Andy Nguyen
- Ronald O. Perelman Department of Dermatology, New York University Grossman School of Medicine, New York, New York
| | - Randie H Kim
- Ronald O. Perelman Department of Dermatology, New York University Grossman School of Medicine, New York, New York
| | - Kristen Lo Sicco
- Ronald O. Perelman Department of Dermatology, New York University Grossman School of Medicine, New York, New York
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14
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Wang T, Zhang Q, Wang N, Liu Z, Zhang B, Zhao Y. Research Progresses of Targeted Therapy and Immunotherapy for Hepatocellular Carcinoma. Curr Med Chem 2021; 28:3107-3146. [PMID: 33050856 DOI: 10.2174/0929867327666201013162144] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/30/2020] [Revised: 08/25/2020] [Accepted: 09/01/2020] [Indexed: 12/24/2022]
Abstract
Hepatocellular carcinoma (HCC) is one of the most common malignant tumors worldwide, with nearly one million new cases and deaths every year. Owing to the complex pathogenesis, hidden early symptoms, rapidly developing processes, and poor prognosis, the morbidity and mortality of HCC are increasing yearly. With the progress being made in modern medicine, the treatment of HCC is no longer limited to traditional methods. Targeted therapy and immunotherapy have emerged to treat advanced and metastatic HCC in recent years. Since Sorafenib is the first molecular targeting drug against angiogenesis, targeted drugs for HCC are continually emerging. Moreover, immunotherapy plays a vital role in clinical trials. In particular, the application of immune checkpoint inhibitors, which have received increasing attention in the field of cancer treatment, is a possible research path. Interestingly, these two therapies generally complement each other at some stages of HCC, bringing new hope for patients with advanced HCC. In this paper, we discuss the research progress of targeted therapy and immunotherapy for HCC in recent years, which will provide a reference for the further development of drugs for HCC.
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Affiliation(s)
- Tao Wang
- Institute of Drug Discovery Technology, Ningbo University, Ningbo, Zhejiang 315211, China
| | - Qiting Zhang
- Institute of Drug Discovery Technology, Ningbo University, Ningbo, Zhejiang 315211, China
| | - Ning Wang
- Institute of Drug Discovery Technology, Ningbo University, Ningbo, Zhejiang 315211, China
| | - Ziqi Liu
- Department of Pharmacy, the PLA Rocket Force Characteristic Medical Center, Beijing 100088, China
| | - Bin Zhang
- Li Dak Sum Yip Yio Chin Kenneth Li Marine Biopharmaceutical Research Center, Department of Marine Pharmacy, College of Food and Pharmaceutical Sciences, Ningbo University, Ningbo, Zhejiang 315211, China
| | - Yufen Zhao
- Institute of Drug Discovery Technology, Ningbo University, Ningbo, Zhejiang 315211, China
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15
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Vogel A, Rimassa L, Sun HC, Abou-Alfa GK, El-Khoueiry A, Pinato DJ, Sanchez Alvarez J, Daigl M, Orfanos P, Leibfried M, Blanchet Zumofen MH, Gaillard VE, Merle P. Comparative Efficacy of Atezolizumab plus Bevacizumab and Other Treatment Options for Patients with Unresectable Hepatocellular Carcinoma: A Network Meta-Analysis. Liver Cancer 2021; 10:240-248. [PMID: 34239810 PMCID: PMC8237801 DOI: 10.1159/000515302] [Citation(s) in RCA: 36] [Impact Index Per Article: 9.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/09/2020] [Accepted: 02/12/2021] [Indexed: 02/04/2023] Open
Abstract
BACKGROUND Most phase 3 clinical trials of systemic therapy for first-line unresectable hepatocellular carcinoma (HCC) have failed, with the exception of SHARP, REFLECT, and IMbrave150. We conducted indirect comparisons of therapies evaluated for first-line HCC treatment. SUMMARY We conducted a systematic review and meta-analysis of treatments for adults with locally advanced or metastatic unresectable HCC and no prior systemic treatment, including atezolizu-mab plus bevacizumab, sorafenib, lenvatinib, nivolumab, selective internal radiotherapy (SIRT), transarterial chemoembolization, and placebo or best supportive care. Randomized controlled trials published from January 1, 2007, to March 12, 2020, were retrieved from MEDLINE and Embase. Qualitative assessment of heterogeneity evaluated study designs, populations, and outcomes. Indirect comparisons used generalized linear models with random effects within a Bayesian framework and informative priors. We calculated relative efficacy estimates with 95% credible intervals (CrIs) and Bayesian posterior probability estimates of atezolizumab-bevacizumab being superior to other treatments. Nine clinical studies with a total of 3,897 participants were identified from 8,783 records and used to build the all-trials evidence network. Indirect comparisons suggested an improved overall survival (OS) with atezolizumab-bevacizumab versus lenvatinib (odds ratio, 0.63 [95% CrI 0.39-1.04]; with 97% Bayesian posterior probability of being superior), nivolumab (0.68 [95% CrI 0.41-1.14]; 94%), sorafenib (0.59 [95% CrI 0.39-0.87]; 99%), SIRT (0.51 [95% CrI 0.32-0.82]; 100%), or placebo/best supportive care (0.40 [95% CrI 0.25-0.64]; 100%). KEY MESSAGES Within the context of indirect comparisons, analyses of OS favored atezolizumab-bevacizumab versus other treatment options for patients with locally advanced or metastatic unresectable HCC.
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Affiliation(s)
- Arndt Vogel
- Hannover Medical School, Hannover, Germany,*Arndt Vogel,
| | - Lorenza Rimassa
- Medical Oncology and Hematology Unit, Humanitas Cancer Center, Humanitas Clinical and Research Center, IRCCS and Department of Biomedical Sciences, Humanitas University, Milan, Italy
| | - Hui-Chan Sun
- Department of Liver Surgery and Transplantation, Liver Cancer Institute, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Ghassan K. Abou-Alfa
- Memorial Sloan Kettering Cancer Center and Weill Medical College at Cornell University, New York, New York, USA
| | | | - David J. Pinato
- Department of Surgery and Cancer, Imperial College London, London, United Kingdom
| | | | | | | | | | | | | | - Philippe Merle
- Hepatology Unit, Hôpital de La Croix-Rousse, Lyon, France
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Boilève A, Hilmi M, Delaye M, Tijeras-Raballand A, Neuzillet C. Biomarkers in Hepatobiliary Cancers: What is Useful in Clinical Practice? Cancers (Basel) 2021; 13:2708. [PMID: 34070929 PMCID: PMC8198554 DOI: 10.3390/cancers13112708] [Citation(s) in RCA: 18] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/25/2021] [Revised: 05/25/2021] [Accepted: 05/27/2021] [Indexed: 12/24/2022] Open
Abstract
Hepatocellular carcinoma (HCC) and biliary tract cancers (BTC) exhibit a poor prognosis with 5-year overall survival rates around 15%, all stages combined. Most of these primary liver malignancies are metastatic at diagnostic, with only limited therapeutic options, relying mainly on systemic therapies. Treatment modalities are different yet partially overlapping between HCC and BTC. The complex molecular profile of BTC yields to several actionable therapeutic targets, contrary to HCC that remains the field of antiangiogenic drugs in non-molecularly selected patients. Immunotherapy is now validated in the first line in HCC in combination with bevacizumab, while clinical activity of single agent immunotherapy appears limited to a subset of patients in BTC, still poorly characterized, and combinations are currently under investigation. In this review, we provide a critical evaluation and grading of clinical relevance on (i) the main prognostic biomarkers in HCC and BTC, (ii) the main theragnostic biomarkers in both tumors, and lastly (iii) what is recommended in clinical practice.
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Affiliation(s)
- Alice Boilève
- Gustave Roussy, Département de Médecine Oncologique, 94805 Villejuif, France;
- GERCOR Group, 151 rue du Faubourg Saint-Antoine, 75011 Paris, France; (M.H.); (M.D.); (A.T.-R.)
| | - Marc Hilmi
- GERCOR Group, 151 rue du Faubourg Saint-Antoine, 75011 Paris, France; (M.H.); (M.D.); (A.T.-R.)
- Département de Médecine Oncologique, Curie Institute, 92210 Saint-Cloud, France
| | - Matthieu Delaye
- GERCOR Group, 151 rue du Faubourg Saint-Antoine, 75011 Paris, France; (M.H.); (M.D.); (A.T.-R.)
- Département de Médecine Oncologique, Curie Institute, 92210 Saint-Cloud, France
| | - Annemilaï Tijeras-Raballand
- GERCOR Group, 151 rue du Faubourg Saint-Antoine, 75011 Paris, France; (M.H.); (M.D.); (A.T.-R.)
- OncoMEGA, 75010 Paris, France
| | - Cindy Neuzillet
- GERCOR Group, 151 rue du Faubourg Saint-Antoine, 75011 Paris, France; (M.H.); (M.D.); (A.T.-R.)
- Département de Médecine Oncologique, Curie Institute, 92210 Saint-Cloud, France
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Han Y, Zhi WH, Xu F, Zhang CB, Huang XQ, Luo JF. Selection of first-line systemic therapies for advanced hepatocellular carcinoma: A network meta-analysis of randomized controlled trials. World J Gastroenterol 2021; 27:2415-2433. [PMID: 34040331 PMCID: PMC8130040 DOI: 10.3748/wjg.v27.i19.2415] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/26/2021] [Revised: 03/10/2021] [Accepted: 04/21/2021] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND The majority of clinical trials of first-line systemic treatments for hepatocellular carcinoma (HCC) used placebo or sorafenib as comparators, and there are limited data providing a cross comparison of treatments in this setting, especially for newly-approved immune checkpoint inhibitor and vascular endothelial growth factor inhibitor combination treatments. AIM To systematically review and compare response rates, survival outcomes, and safety of first-line systemic therapies for advanced hepatocellular carcinoma. METHODS We searched PubMed, Science Direct, the Cochrane Database, Excerpta Medica Database, and abstracts from the American Society of Clinical Oncology 2020 annual congress. Eligible studies were randomized controlled trials of systemic therapy enrolling adults with advanced/unresectable HCC. Risk of bias was assessed with the Cochrane risk of bias tool for randomized controlled trials. A network meta-analysis was used to synthesize data and perform direct and indirect comparisons between treatments. P value, a frequentist analog to the surface under the cumulative ranking curve, was used to rank treatments. RESULTS In total, 1398 articles were screened and 27 included. Treatments compared were atezolizumab plus bevacizumab, brivanib, donafenib, dovitinib, FOLFOX4, lenvatinib, linifanib, nintedanib, nivolumab, sorafenib, sunitinib, vandetanib, 11 sorafenib combination therapies, and three other combination therapies. For overall response rate, lenvatinib ranked 1/19, followed by atezolizumab plus bevacizumab and nivolumab. For progression-free survival (PFS), atezolizumab + bevacizumab was ranked 1/15, followed by lenvatinib. With the exception of atezolizumab + bevacizumab [hazard ratios (HR)PFS = 0.90; 95% confidence interval (CI): 0.64-1.25], the estimated HRs for PFS for all included treatments vs lenvatinib were > 1; however, the associated 95%CI passed through unity for bevacizumab plus erlotinib, linifanib, and FOLFOX4. For overall survival, atezolizumab plus bevacizumab was ranked 1/25, followed by vandetanib 100 mg/d and donafinib, with lenvatinib ranked 6/25. Atezolizumab + bevacizumab was associated with a lower risk of death vs lenvatinib (HRos = 0.63; 95%CI: 0.44-0.89), while the HR for overall survival for most other treatments vs lenvatinib had associated 95%CIs that passed through unity. Vandetanib 300 mg/d and 100 mg/d were ranked 1/13 and 2/13, respectively, for the lowest incidence of treatment terminations due to adverse events, followed by sorafenib (5/13), lenvatinib (10/13), and atezolizumab + bevacizumab (13/13). CONCLUSION There is not one single first-line treatment for advanced HCC associated with superior outcomes across all outcome measurements. Therefore, first-line systemic treatment should be selected based on individualized treatment goals.
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Affiliation(s)
- Yue Han
- Department of Interventional Therapy, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China
| | - Wei-Hua Zhi
- Department of Interventional Therapy, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China
| | - Fei Xu
- Department of Interventional Therapy, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China
| | - Chen-Bo Zhang
- Department of Biostatistics, School of Public Health, Fudan University, Shanghai 200034, China
| | - Xiao-Qian Huang
- Department of Biostatistics, School of Public Health, Fudan University, Shanghai 200034, China
| | - Jian-Feng Luo
- Department of Biostatistics, School of Public Health, Fudan University, Shanghai 200034, China
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FGF/FGFR Signaling in Hepatocellular Carcinoma: From Carcinogenesis to Recent Therapeutic Intervention. Cancers (Basel) 2021; 13:cancers13061360. [PMID: 33802841 PMCID: PMC8002748 DOI: 10.3390/cancers13061360] [Citation(s) in RCA: 28] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/16/2021] [Revised: 03/11/2021] [Accepted: 03/13/2021] [Indexed: 12/16/2022] Open
Abstract
Simple Summary As the most common primary liver cancer, HCC is a tricky cancer resistant to systemic therapies. The fibroblast growth factor family and its receptors are gaining more and more attention in various cancers. Noticing an explosion in the number of studies about aberrant FGF/FGFR signaling in HCC being studied, we were encouraged to summarize them. This review discusses how FGF/FGFR signaling influences HCC development and its implications in HCC prediction and target treatment, and combination treatment. Abstract Hepatocellular carcinoma (HCC) is the most common type of primary liver cancer, ranking third in cancer deaths worldwide. Over the last decade, several studies have emphasized the development of tyrosine kinase inhibitors (TKIs) to target the aberrant pathways in HCC. However, the outcomes are far from satisfactory due to the increasing resistance and adverse effects. The family of fibroblast growth factor (FGF) and its receptors (FGFR) are involved in various biological processes, including embryogenesis, morphogenesis, wound repair, and cell growth. The aberrant FGF/FGFR signaling is also observed in multiple cancers, including HCC. Anti-FGF/FGFR provides delightful benefits for cancer patients, especially those with FGF signaling alteration. More and more multi-kinase inhibitors targeting FGF signaling, pan-FGFR inhibitors, and selective FGFR inhibitors are now under preclinical and clinical investigation. This review summarizes the aberrant FGF/FGFR signaling in HCC initiating, development and treatment status, and provide new insights into the treatment of HCC.
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Donisi C, Puzzoni M, Ziranu P, Lai E, Mariani S, Saba G, Impera V, Dubois M, Persano M, Migliari M, Pretta A, Liscia N, Astara G, Scartozzi M. Immune Checkpoint Inhibitors in the Treatment of HCC. Front Oncol 2021; 10:601240. [PMID: 33585218 PMCID: PMC7874239 DOI: 10.3389/fonc.2020.601240] [Citation(s) in RCA: 84] [Impact Index Per Article: 21.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/31/2020] [Accepted: 11/11/2020] [Indexed: 12/24/2022] Open
Abstract
Hepatocellular carcinoma (HCC) is the typical inflammation-induced neoplasia. It often prospers where a chronic liver disease persists, thus leading a strong rationale for immune therapy. Several immune-based treatments, including immune checkpoint inhibitors (ICI), cytokines, adoptive cell transfer, and vaccines, have been tested in the treatment of HCC. In this review, we summarize the role of the ICI in HCC patients in various sets of treatment. As for advanced HCC, the anti-Programmed cell Death protein 1 (PD1) antibodies and the anti-Cytotoxic T-Lymphocyte Antigen 4 (CTLA-4) antibodies have been examined in patients with enthusiastic results in phase I-II-III studies. Overall, this led the Food and Drug Administration (FDA) to approve pembrolizumab, nivolumab, and nivolumab + ipilimumab in the second-line setting. The anti- Programmed Death-Ligand 1 (PDL-1) antibodies have also been evaluated. Thanks to the results obtained from phase III IMbrave study, atezolizumab + bevacizumab is now the standard of care in the first-line advanced setting of HCC. As for localized HCC, the putative immunological effect of locoregional therapies led to evaluate the combination strategy with ICI. This way, chemoembolization, ablation with radiofrequency, and radioembolization combined with ICI are currently under study. Likewise, the study of adjuvant immunotherapy following surgical resection is underway. In addition, the different ICI has been studied in combination with other ICI as well as with multikinase inhibitors and anti-angiogenesis monoclonal antibody. The evidence available suggests that combining systemic therapies and locoregional treatments with ICI may represent an effective strategy in this context.
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Affiliation(s)
- Clelia Donisi
- Medical Oncology Unit, University Hospital and University of Cagliari, Cagliari, Italy
| | - Marco Puzzoni
- Medical Oncology Unit, University Hospital and University of Cagliari, Cagliari, Italy
| | - Pina Ziranu
- Medical Oncology Unit, University Hospital and University of Cagliari, Cagliari, Italy
| | - Eleonora Lai
- Medical Oncology Unit, University Hospital and University of Cagliari, Cagliari, Italy
| | - Stefano Mariani
- Medical Oncology Unit, University Hospital and University of Cagliari, Cagliari, Italy
| | - Giorgio Saba
- Medical Oncology Unit, University Hospital and University of Cagliari, Cagliari, Italy
| | - Valentino Impera
- Medical Oncology Unit, University Hospital and University of Cagliari, Cagliari, Italy
- Medical Oncology Unit, Sapienza University of Rome, Rome, Italy
| | - Marco Dubois
- Medical Oncology Unit, University Hospital and University of Cagliari, Cagliari, Italy
| | - Mara Persano
- Medical Oncology Unit, University Hospital and University of Cagliari, Cagliari, Italy
| | - Marco Migliari
- Medical Oncology Unit, University Hospital and University of Cagliari, Cagliari, Italy
| | - Andrea Pretta
- Medical Oncology Unit, University Hospital and University of Cagliari, Cagliari, Italy
- Medical Oncology Unit, Sapienza University of Rome, Rome, Italy
| | - Nicole Liscia
- Medical Oncology Unit, University Hospital and University of Cagliari, Cagliari, Italy
- Medical Oncology Unit, Sapienza University of Rome, Rome, Italy
| | - Giorgio Astara
- Medical Oncology Unit, University Hospital and University of Cagliari, Cagliari, Italy
| | - Mario Scartozzi
- Medical Oncology Unit, University Hospital and University of Cagliari, Cagliari, Italy
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Lee J, Sung PS, Yang H, Lee SK, Nam HC, Yoo SH, Lee HL, Kim HY, Lee SW, Kwon JH, Jang JW, Kim CW, Nam SW, Bae SH, Choi JY, Yoon SK. A Real-World Comparative Analysis of Lenvatinib and Sorafenib as a Salvage Therapy for Transarterial Treatments in Unresectable HCC. J Clin Med 2020; 9:4121. [PMID: 33371271 PMCID: PMC7767204 DOI: 10.3390/jcm9124121] [Citation(s) in RCA: 23] [Impact Index Per Article: 4.6] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/01/2020] [Accepted: 12/18/2020] [Indexed: 12/15/2022] Open
Abstract
BACKGROUND/AIMS Lenvatinib was recently approved as a first-line oral multikinase inhibitor for unresectable hepatocellular carcinoma (HCC). In this study, we aimed to compare the efficacy and safety of lenvatinib and sorafenib for the treatment of unresectable HCC in patients with prior failure of transarterial treatment. METHODS Between January 2019 and September 2020, 98 unresectable HCC patients treated with lenvatinib or sorafenib as salvage therapy were enrolled from five Korean university-affiliated hospitals. Progression-free survival (PFS), overall survival (OS), objective response rate (ORR), and disease control rate were calculated to assess the antitumor response. RESULTS A total of 43 and 55 patients were treated with lenvatinib and sorafenib, respectively, as salvage therapy after the failure of transarterial treatments. The median PFS was 4.97 months in the lenvatinib group and 2.47 months in the sorafenib group (p = 0.001, log-rank test). The ORR was significantly higher in the lenvatinib group (25.6%) than in the sorafenib group (3.6%, p = 0.002). Use of lenvatinib over sorafenib (hazard ratio: 0.359, 95% confidence interval: 0.203-0.635, p < 0.001) was the most significant factor for a favorable PFS after the failure of transarterial treatments in all enrolled patients. For favorable OS, achieving objective response was the significant factor (hazard ratio 0.356, 95% confidence interval: 0.132-0.957, p = 0.041). There were no significant differences in the safety profile between the two groups. CONCLUSIONS In this real-world study, lenvatinib was demonstrated to be more efficacious than sorafenib as a salvage therapy for transarterial treatments in unresectable HCC.
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Affiliation(s)
- Jaejun Lee
- The Catholic University Liver Research Center, College of Medicine, The Catholic University of Korea, Seoul 06591, Korea; (J.L.); (H.Y.); (S.K.L.); (H.C.N.); (S.H.Y.); (H.L.L.); (H.Y.K.); (S.W.L.); (J.H.K.); (J.W.J.); (C.W.K.); (S.W.N.); (S.H.B.); (J.Y.C.); (S.K.Y.)
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, College of Medicine, Eunpyeong St. Mary’s Hospital, The Catholic University of Korea, Seoul 03382, Korea
| | - Pil Soo Sung
- The Catholic University Liver Research Center, College of Medicine, The Catholic University of Korea, Seoul 06591, Korea; (J.L.); (H.Y.); (S.K.L.); (H.C.N.); (S.H.Y.); (H.L.L.); (H.Y.K.); (S.W.L.); (J.H.K.); (J.W.J.); (C.W.K.); (S.W.N.); (S.H.B.); (J.Y.C.); (S.K.Y.)
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, College of Medicine, Seoul St. Mary’s Hospital, The Catholic University of Korea, Seoul 06591, Korea
| | - Hyun Yang
- The Catholic University Liver Research Center, College of Medicine, The Catholic University of Korea, Seoul 06591, Korea; (J.L.); (H.Y.); (S.K.L.); (H.C.N.); (S.H.Y.); (H.L.L.); (H.Y.K.); (S.W.L.); (J.H.K.); (J.W.J.); (C.W.K.); (S.W.N.); (S.H.B.); (J.Y.C.); (S.K.Y.)
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, College of Medicine, Eunpyeong St. Mary’s Hospital, The Catholic University of Korea, Seoul 03382, Korea
| | - Soon Kyu Lee
- The Catholic University Liver Research Center, College of Medicine, The Catholic University of Korea, Seoul 06591, Korea; (J.L.); (H.Y.); (S.K.L.); (H.C.N.); (S.H.Y.); (H.L.L.); (H.Y.K.); (S.W.L.); (J.H.K.); (J.W.J.); (C.W.K.); (S.W.N.); (S.H.B.); (J.Y.C.); (S.K.Y.)
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, College of Medicine, Seoul St. Mary’s Hospital, The Catholic University of Korea, Seoul 06591, Korea
| | - Hee Chul Nam
- The Catholic University Liver Research Center, College of Medicine, The Catholic University of Korea, Seoul 06591, Korea; (J.L.); (H.Y.); (S.K.L.); (H.C.N.); (S.H.Y.); (H.L.L.); (H.Y.K.); (S.W.L.); (J.H.K.); (J.W.J.); (C.W.K.); (S.W.N.); (S.H.B.); (J.Y.C.); (S.K.Y.)
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, College of Medicine, Eunpyeong St. Mary’s Hospital, The Catholic University of Korea, Seoul 03382, Korea
| | - Sun Hong Yoo
- The Catholic University Liver Research Center, College of Medicine, The Catholic University of Korea, Seoul 06591, Korea; (J.L.); (H.Y.); (S.K.L.); (H.C.N.); (S.H.Y.); (H.L.L.); (H.Y.K.); (S.W.L.); (J.H.K.); (J.W.J.); (C.W.K.); (S.W.N.); (S.H.B.); (J.Y.C.); (S.K.Y.)
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, College of Medicine, Incheon St. Mary’s Hospital, The Catholic University of Korea, Seoul 22711, Korea
| | - Hae Lim Lee
- The Catholic University Liver Research Center, College of Medicine, The Catholic University of Korea, Seoul 06591, Korea; (J.L.); (H.Y.); (S.K.L.); (H.C.N.); (S.H.Y.); (H.L.L.); (H.Y.K.); (S.W.L.); (J.H.K.); (J.W.J.); (C.W.K.); (S.W.N.); (S.H.B.); (J.Y.C.); (S.K.Y.)
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, College of Medicine, Bucheon St. Mary’s Hospital, The Catholic University of Korea, Seoul 14647, Korea
| | - Hee Yeon Kim
- The Catholic University Liver Research Center, College of Medicine, The Catholic University of Korea, Seoul 06591, Korea; (J.L.); (H.Y.); (S.K.L.); (H.C.N.); (S.H.Y.); (H.L.L.); (H.Y.K.); (S.W.L.); (J.H.K.); (J.W.J.); (C.W.K.); (S.W.N.); (S.H.B.); (J.Y.C.); (S.K.Y.)
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, College of Medicine, Uijeongbu St. Mary’s Hospital, The Catholic University of Korea, Seoul 11765, Korea
| | - Sung Won Lee
- The Catholic University Liver Research Center, College of Medicine, The Catholic University of Korea, Seoul 06591, Korea; (J.L.); (H.Y.); (S.K.L.); (H.C.N.); (S.H.Y.); (H.L.L.); (H.Y.K.); (S.W.L.); (J.H.K.); (J.W.J.); (C.W.K.); (S.W.N.); (S.H.B.); (J.Y.C.); (S.K.Y.)
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, College of Medicine, Bucheon St. Mary’s Hospital, The Catholic University of Korea, Seoul 14647, Korea
| | - Jung Hyun Kwon
- The Catholic University Liver Research Center, College of Medicine, The Catholic University of Korea, Seoul 06591, Korea; (J.L.); (H.Y.); (S.K.L.); (H.C.N.); (S.H.Y.); (H.L.L.); (H.Y.K.); (S.W.L.); (J.H.K.); (J.W.J.); (C.W.K.); (S.W.N.); (S.H.B.); (J.Y.C.); (S.K.Y.)
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, College of Medicine, Incheon St. Mary’s Hospital, The Catholic University of Korea, Seoul 22711, Korea
| | - Jeong Won Jang
- The Catholic University Liver Research Center, College of Medicine, The Catholic University of Korea, Seoul 06591, Korea; (J.L.); (H.Y.); (S.K.L.); (H.C.N.); (S.H.Y.); (H.L.L.); (H.Y.K.); (S.W.L.); (J.H.K.); (J.W.J.); (C.W.K.); (S.W.N.); (S.H.B.); (J.Y.C.); (S.K.Y.)
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, College of Medicine, Seoul St. Mary’s Hospital, The Catholic University of Korea, Seoul 06591, Korea
| | - Chang Wook Kim
- The Catholic University Liver Research Center, College of Medicine, The Catholic University of Korea, Seoul 06591, Korea; (J.L.); (H.Y.); (S.K.L.); (H.C.N.); (S.H.Y.); (H.L.L.); (H.Y.K.); (S.W.L.); (J.H.K.); (J.W.J.); (C.W.K.); (S.W.N.); (S.H.B.); (J.Y.C.); (S.K.Y.)
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, College of Medicine, Uijeongbu St. Mary’s Hospital, The Catholic University of Korea, Seoul 11765, Korea
| | - Soon Woo Nam
- The Catholic University Liver Research Center, College of Medicine, The Catholic University of Korea, Seoul 06591, Korea; (J.L.); (H.Y.); (S.K.L.); (H.C.N.); (S.H.Y.); (H.L.L.); (H.Y.K.); (S.W.L.); (J.H.K.); (J.W.J.); (C.W.K.); (S.W.N.); (S.H.B.); (J.Y.C.); (S.K.Y.)
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, College of Medicine, Incheon St. Mary’s Hospital, The Catholic University of Korea, Seoul 22711, Korea
| | - Si Hyun Bae
- The Catholic University Liver Research Center, College of Medicine, The Catholic University of Korea, Seoul 06591, Korea; (J.L.); (H.Y.); (S.K.L.); (H.C.N.); (S.H.Y.); (H.L.L.); (H.Y.K.); (S.W.L.); (J.H.K.); (J.W.J.); (C.W.K.); (S.W.N.); (S.H.B.); (J.Y.C.); (S.K.Y.)
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, College of Medicine, Eunpyeong St. Mary’s Hospital, The Catholic University of Korea, Seoul 03382, Korea
| | - Jong Young Choi
- The Catholic University Liver Research Center, College of Medicine, The Catholic University of Korea, Seoul 06591, Korea; (J.L.); (H.Y.); (S.K.L.); (H.C.N.); (S.H.Y.); (H.L.L.); (H.Y.K.); (S.W.L.); (J.H.K.); (J.W.J.); (C.W.K.); (S.W.N.); (S.H.B.); (J.Y.C.); (S.K.Y.)
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, College of Medicine, Seoul St. Mary’s Hospital, The Catholic University of Korea, Seoul 06591, Korea
| | - Seung Kew Yoon
- The Catholic University Liver Research Center, College of Medicine, The Catholic University of Korea, Seoul 06591, Korea; (J.L.); (H.Y.); (S.K.L.); (H.C.N.); (S.H.Y.); (H.L.L.); (H.Y.K.); (S.W.L.); (J.H.K.); (J.W.J.); (C.W.K.); (S.W.N.); (S.H.B.); (J.Y.C.); (S.K.Y.)
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, College of Medicine, Seoul St. Mary’s Hospital, The Catholic University of Korea, Seoul 06591, Korea
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21
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Lai E, Astara G, Ziranu P, Pretta A, Migliari M, Dubois M, Donisi C, Mariani S, Liscia N, Impera V, Persano M, Tolu S, Balconi F, Pinna G, Spanu D, Pireddu A, Saba G, Camera S, Musio F, Puzzoni M, Pusceddu V, Madeddu C, Casadei Gardini A, Scartozzi M. Introducing immunotherapy for advanced hepatocellular carcinoma patients: Too early or too fast? Crit Rev Oncol Hematol 2020; 157:103167. [PMID: 33271389 DOI: 10.1016/j.critrevonc.2020.103167] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/20/2020] [Revised: 11/02/2020] [Accepted: 11/05/2020] [Indexed: 02/06/2023] Open
Abstract
Advanced hepatocellular carcinoma (HCC) is the most frequent liver cancer. Immunotherapy has been explored in this disease in order to improve survival outcomes. Nowadays, scientific research is focusing especially on immune checkpoint inhibitors, in particular anti-PD1, anti-PD-L1 and anti-CTLA4 monoclonal antibodies (mAbs), as single-agent or in combination with other immunotherapy agents, target therapies, anti-vascular endothelial growth factor (VEGF) and other agents targeting specific molecular pathways. Other immunotherapy strategies have been assessed or are under investigation in advanced HCC, namely cytokines, adoptive cell therapy, oncolytic virus, cancer vaccines. Each treatment presents specific efficacy and toxicity profiles, strictly related to their mechanism of action and to advanced HCC tumour microenvironment (TME). The aim of this review is to outline the state-of-the-art of immunotherapy in advanced HCC treatment, highlighting data on already investigated treatment strategies, safety and toxicity (including HBV/HCV-related HCC), and ongoing clinical trials focusing on new promising therapeutic weapons.
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Affiliation(s)
- Eleonora Lai
- Medical Oncology Unit, University Hospital and University of Cagliari, Cagliari, Italy. Oncologia Medica, Azienda Ospedaliera Universitaria di Cagliari, Presidio Policlinico Universitario "Duilio Casula" S.S. 554, Km 4,500 Bivio per Sestu, 09042 Monserrato, Cagliari, Italy.
| | - Giorgio Astara
- Medical Oncology Unit, University Hospital and University of Cagliari, Cagliari, Italy. Oncologia Medica, Azienda Ospedaliera Universitaria di Cagliari, Presidio Policlinico Universitario "Duilio Casula" S.S. 554, Km 4,500 Bivio per Sestu, 09042 Monserrato, Cagliari, Italy.
| | - Pina Ziranu
- Medical Oncology Unit, University Hospital and University of Cagliari, Cagliari, Italy. Oncologia Medica, Azienda Ospedaliera Universitaria di Cagliari, Presidio Policlinico Universitario "Duilio Casula" S.S. 554, Km 4,500 Bivio per Sestu, 09042 Monserrato, Cagliari, Italy.
| | - Andrea Pretta
- Medical Oncology Unit, Sapienza University of Rome - University Hospital and University of Cagliari, Cagliari, Italy. Oncologia Medica, Azienda Ospedaliera Universitaria di Cagliari, Presidio Policlinico Universitario "Duilio Casula" S.S. 554, Km 4,500 Bivio per Sestu, 09042 Monserrato, Cagliari, Italy.
| | - Marco Migliari
- Medical Oncology Unit, University Hospital and University of Cagliari, Cagliari, Italy. Oncologia Medica, Azienda Ospedaliera Universitaria di Cagliari, Presidio Policlinico Universitario "Duilio Casula" S.S. 554, Km 4,500 Bivio per Sestu, 09042 Monserrato, Cagliari, Italy.
| | - Marco Dubois
- Medical Oncology Unit, University Hospital and University of Cagliari, Cagliari, Italy. Oncologia Medica, Azienda Ospedaliera Universitaria di Cagliari, Presidio Policlinico Universitario "Duilio Casula" S.S. 554, Km 4,500 Bivio per Sestu, 09042 Monserrato, Cagliari, Italy.
| | - Clelia Donisi
- Medical Oncology Unit, University Hospital and University of Cagliari, Cagliari, Italy. Oncologia Medica, Azienda Ospedaliera Universitaria di Cagliari, Presidio Policlinico Universitario "Duilio Casula" S.S. 554, Km 4,500 Bivio per Sestu, 09042 Monserrato, Cagliari, Italy.
| | - Stefano Mariani
- Medical Oncology Unit, University Hospital and University of Cagliari, Cagliari, Italy. Oncologia Medica, Azienda Ospedaliera Universitaria di Cagliari, Presidio Policlinico Universitario "Duilio Casula" S.S. 554, Km 4,500 Bivio per Sestu, 09042 Monserrato, Cagliari, Italy.
| | - Nicole Liscia
- Medical Oncology Unit, Sapienza University of Rome - University Hospital and University of Cagliari, Cagliari, Italy. Oncologia Medica, Azienda Ospedaliera Universitaria di Cagliari, Presidio Policlinico Universitario "Duilio Casula" S.S. 554, Km 4,500 Bivio per Sestu, 09042 Monserrato, Cagliari, Italy.
| | - Valentino Impera
- Medical Oncology Unit, Sapienza University of Rome - University Hospital and University of Cagliari, Cagliari, Italy. Oncologia Medica, Azienda Ospedaliera Universitaria di Cagliari, Presidio Policlinico Universitario "Duilio Casula" S.S. 554, Km 4,500 Bivio per Sestu, 09042 Monserrato, Cagliari, Italy.
| | - Mara Persano
- Medical Oncology Unit, University Hospital and University of Cagliari, Cagliari, Italy. Oncologia Medica, Azienda Ospedaliera Universitaria di Cagliari, Presidio Policlinico Universitario "Duilio Casula" S.S. 554, Km 4,500 Bivio per Sestu, 09042 Monserrato, Cagliari, Italy.
| | - Simona Tolu
- Medical Oncology Unit, Sapienza University of Rome - University Hospital and University of Cagliari, Cagliari, Italy. Oncologia Medica, Azienda Ospedaliera Universitaria di Cagliari, Presidio Policlinico Universitario "Duilio Casula" S.S. 554, Km 4,500 Bivio per Sestu, 09042 Monserrato, Cagliari, Italy.
| | - Francesca Balconi
- Medical Oncology Unit, University Hospital and University of Cagliari, Cagliari, Italy. Oncologia Medica, Azienda Ospedaliera Universitaria di Cagliari, Presidio Policlinico Universitario "Duilio Casula" S.S. 554, Km 4,500 Bivio per Sestu, 09042 Monserrato, Cagliari, Italy.
| | - Giovanna Pinna
- Medical Oncology Unit, University Hospital and University of Cagliari, Cagliari, Italy. Oncologia Medica, Azienda Ospedaliera Universitaria di Cagliari, Presidio Policlinico Universitario "Duilio Casula" S.S. 554, Km 4,500 Bivio per Sestu, 09042 Monserrato, Cagliari, Italy.
| | - Dario Spanu
- Medical Oncology Unit, University Hospital and University of Cagliari, Cagliari, Italy. Oncologia Medica, Azienda Ospedaliera Universitaria di Cagliari, Presidio Policlinico Universitario "Duilio Casula" S.S. 554, Km 4,500 Bivio per Sestu, 09042 Monserrato, Cagliari, Italy.
| | - Annagrazia Pireddu
- Medical Oncology Unit, Sapienza University of Rome - University Hospital and University of Cagliari, Cagliari, Italy. Oncologia Medica, Azienda Ospedaliera Universitaria di Cagliari, Presidio Policlinico Universitario "Duilio Casula" S.S. 554, Km 4,500 Bivio per Sestu, 09042 Monserrato, Cagliari, Italy.
| | - Giorgio Saba
- Medical Oncology Unit, University Hospital and University of Cagliari, Cagliari, Italy. Oncologia Medica, Azienda Ospedaliera Universitaria di Cagliari, Presidio Policlinico Universitario "Duilio Casula" S.S. 554, Km 4,500 Bivio per Sestu, 09042 Monserrato, Cagliari, Italy.
| | - Silvia Camera
- Department of Medical Oncology, Università Vita-Salute, San Raffaele Hospital IRCCS, 20019, Milan, Italy. Dipartimento di Oncologia, IRCCS Ospedale San Raffaele, via Olgettina 60, Milan, Italy.
| | - Francesca Musio
- Medical Oncology Unit, University Hospital and University of Cagliari, Cagliari, Italy. Oncologia Medica, Azienda Ospedaliera Universitaria di Cagliari, Presidio Policlinico Universitario "Duilio Casula" S.S. 554, Km 4,500 Bivio per Sestu, 09042 Monserrato, Cagliari, Italy.
| | - Marco Puzzoni
- Medical Oncology Unit, University Hospital and University of Cagliari, Cagliari, Italy. Oncologia Medica, Azienda Ospedaliera Universitaria di Cagliari, Presidio Policlinico Universitario "Duilio Casula" S.S. 554, Km 4,500 Bivio per Sestu, 09042 Monserrato, Cagliari, Italy.
| | - Valeria Pusceddu
- Medical Oncology Unit, University Hospital and University of Cagliari, Cagliari, Italy. Oncologia Medica, Azienda Ospedaliera Universitaria di Cagliari, Presidio Policlinico Universitario "Duilio Casula" S.S. 554, Km 4,500 Bivio per Sestu, 09042 Monserrato, Cagliari, Italy.
| | - Clelia Madeddu
- Medical Oncology Unit, University Hospital and University of Cagliari, Cagliari, Italy. Oncologia Medica, Azienda Ospedaliera Universitaria di Cagliari, Presidio Policlinico Universitario "Duilio Casula" S.S. 554, Km 4,500 Bivio per Sestu, 09042 Monserrato, Cagliari, Italy.
| | - Andrea Casadei Gardini
- Department of Medical Oncology, Università Vita-Salute, San Raffaele Hospital IRCCS, 20019, Milan, Italy. Dipartimento di Oncologia, IRCCS Ospedale San Raffaele, via Olgettina 60, Milan, Italy.
| | - Mario Scartozzi
- Medical Oncology Unit, University Hospital and University of Cagliari, Cagliari, Italy. Oncologia Medica, Azienda Ospedaliera Universitaria di Cagliari, Presidio Policlinico Universitario "Duilio Casula" S.S. 554, Km 4,500 Bivio per Sestu, 09042 Monserrato, Cagliari, Italy.
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22
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Chen Z, Xie H, Hu M, Huang T, Hu Y, Sang N, Zhao Y. Recent progress in treatment of hepatocellular carcinoma. Am J Cancer Res 2020; 10:2993-3036. [PMID: 33042631 PMCID: PMC7539784] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/20/2020] [Accepted: 06/28/2020] [Indexed: 06/11/2023] Open
Abstract
Hepatocellular carcinoma (HCC) is the fourth leading cause of cancer-related death worldwide. In the past decade, there have been improvements in non-drug therapies and drug therapies for HCC treatment. Non-drug therapies include hepatic resection, liver transplantation, transarterial chemoembolization (TACE) and ablation. The former two surgical treatments are beneficial for patients with early and mid-stage HCC. As the first choice for non-surgical treatment, different TACE methods has been developed and widely used in combination therapy. Ablation has become an important alternative therapy for the treatment of small HCC or cases of unresectable surgery. Meanwhile, the drugs including small molecule targeted drugs like sorafenib and lenvatinib, monoclonal antibodies such as nivolumab are mainly used for the systematic treatment of advanced HCC. Besides strategies described above are recommended as first-line therapies due to their significant increase in mean overall survival, there are also potential drugs in clinical trials or under preclinical development. In addition, a number of potential preclinical surgical or adjuvant therapies are being studied, such as oncolytic virus, mesenchymal stem cells, biological clock, gut microbiome composition and peptide vaccine, all of which have shown different degrees of inhibition on HCC. With some potential anti-HCC drugs being reported, many promising therapeutic targets in related taxonomic signaling pathways including cell cycle, epigenetics, tyrosine kinase and so on that affect the progression of HCC have also been found. Together, the rational application of existing therapies and drugs as well as the new strategies will bring a bright future for the global cure of HCC in the coming decades.
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Affiliation(s)
- Zhiqian Chen
- West China School of Pharmacy, Sichuan UniversityChengdu 610041, China
| | - Hao Xie
- West China School of Pharmacy, Sichuan UniversityChengdu 610041, China
| | - Mingming Hu
- West China School of Pharmacy, Sichuan UniversityChengdu 610041, China
| | - Tianyi Huang
- West China School of Pharmacy, Sichuan UniversityChengdu 610041, China
| | - Yanan Hu
- West China School of Pharmacy, Sichuan UniversityChengdu 610041, China
| | - Na Sang
- Cancer Center, West China Hospital, West China Medical School, and Collaborative Innovation Center for Biotherapy, Sichuan UniversityChengdu 610041, China
| | - Yinglan Zhao
- West China School of Pharmacy, Sichuan UniversityChengdu 610041, China
- Cancer Center, West China Hospital, West China Medical School, and Collaborative Innovation Center for Biotherapy, Sichuan UniversityChengdu 610041, China
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23
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Wang DX, Yang X, Lin JZ, Bai Y, Long JY, Yang XB, Seery S, Zhao HT. Efficacy and safety of lenvatinib for patients with advanced hepatocellular carcinoma: A retrospective, real-world study conducted in China. World J Gastroenterol 2020. [PMID: 32874058 DOI: 10.3748/wjg.v26.i30.4465.] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/24/2022] Open
Abstract
BACKGROUND Lenvatinib has become an indispensable part of treatment regimens for patients with advanced hepatocellular carcinoma (aHCC). Several recent real-world studies appear to have confirmed this; however, there are etiological differences. This necessitates further real-world studies of lenvatinib across diverse populations, such as in China. AIM To investigate the efficacy and safety of lenvatinib in a Chinese HCC patient population under real-world conditions. METHODS This is a retrospective and multiregional study involving patients with aHCC receiving lenvatinib monotherapy. Efficacy was assessed using the Response Evaluation Criteria in Solid Tumors version 1.1. Baseline characteristics and adverse events (AEs) were recorded throughout the entire study. RESULTS In total, 54 HCC patients treated with lenvatinib monotherapy were included for final analysis. The objective response rate was 22% (n = 12) with a progression-free survival (PFS) of 168 d; however, AEs occurred in 92.8% of patients. Multivariate analysis showed that the Barcelona Clinic Liver Cancer stage [hazard ratio (HR) 0.465; 95%CI: 0.23-0.93; P = 0.031], portal vein tumor thrombus (HR 0.38; 95%CI: 0.15-0.94; P = 0.037) and Child-Pugh classifications (HR 0.468; 95%CI: 0.22-0.97; P = 0.042) were significant factors affecting PFS. The sensitivity (56.7%) and specificity (83.3%) of decreasing serum biomarkers including alpha-fetoprotein were calculated in order to predict tumor size reduction. Gene sequencing also provided insights into potential gene mutation signatures related to the effect of lenvatinib. CONCLUSION Our findings confirm previous evidence from the phase III REFLECT study. The majority of patients in this Chinese sample were suffering from concomitant hepatitis B virus-related HCC. However, further analysis suggested that baseline characteristics, changes in serum biomarkers and gene sequencing may hold the key for predicting lenvatinib responses. Further large-scale prospective studies that incorporate more basic medical science measures should be conducted.
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Affiliation(s)
- Dong-Xu Wang
- Department of Liver Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100730, China
| | - Xu Yang
- Department of Liver Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100730, China
| | - Jian-Zhen Lin
- Department of Liver Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100730, China
| | - Yi Bai
- Department of Liver Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100730, China
| | - Jun-Yu Long
- Department of Liver Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100730, China
| | - Xiao-Bo Yang
- Department of Liver Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100730, China
| | - Samuel Seery
- Department of Humanities, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100730, China
| | - Hai-Tao Zhao
- Department of Liver Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100730, China.
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24
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Wang DX, Yang X, Lin JZ, Bai Y, Long JY, Yang XB, Seery S, Zhao HT. Efficacy and safety of lenvatinib for patients with advanced hepatocellular carcinoma: A retrospective, real-world study conducted in China. World J Gastroenterol 2020; 26:4465-4478. [PMID: 32874058 PMCID: PMC7438196 DOI: 10.3748/wjg.v26.i30.4465] [Citation(s) in RCA: 37] [Impact Index Per Article: 7.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/14/2020] [Revised: 04/25/2020] [Accepted: 07/04/2020] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Lenvatinib has become an indispensable part of treatment regimens for patients with advanced hepatocellular carcinoma (aHCC). Several recent real-world studies appear to have confirmed this; however, there are etiological differences. This necessitates further real-world studies of lenvatinib across diverse populations, such as in China.
AIM To investigate the efficacy and safety of lenvatinib in a Chinese HCC patient population under real-world conditions.
METHODS This is a retrospective and multiregional study involving patients with aHCC receiving lenvatinib monotherapy. Efficacy was assessed using the Response Evaluation Criteria in Solid Tumors version 1.1. Baseline characteristics and adverse events (AEs) were recorded throughout the entire study.
RESULTS In total, 54 HCC patients treated with lenvatinib monotherapy were included for final analysis. The objective response rate was 22% (n = 12) with a progression-free survival (PFS) of 168 d; however, AEs occurred in 92.8% of patients. Multivariate analysis showed that the Barcelona Clinic Liver Cancer stage [hazard ratio (HR) 0.465; 95%CI: 0.23-0.93; P = 0.031], portal vein tumor thrombus (HR 0.38; 95%CI: 0.15-0.94; P = 0.037) and Child-Pugh classifications (HR 0.468; 95%CI: 0.22-0.97; P = 0.042) were significant factors affecting PFS. The sensitivity (56.7%) and specificity (83.3%) of decreasing serum biomarkers including alpha-fetoprotein were calculated in order to predict tumor size reduction. Gene sequencing also provided insights into potential gene mutation signatures related to the effect of lenvatinib.
CONCLUSION Our findings confirm previous evidence from the phase III REFLECT study. The majority of patients in this Chinese sample were suffering from concomitant hepatitis B virus-related HCC. However, further analysis suggested that baseline characteristics, changes in serum biomarkers and gene sequencing may hold the key for predicting lenvatinib responses. Further large-scale prospective studies that incorporate more basic medical science measures should be conducted.
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Affiliation(s)
- Dong-Xu Wang
- Department of Liver Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100730, China
| | - Xu Yang
- Department of Liver Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100730, China
| | - Jian-Zhen Lin
- Department of Liver Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100730, China
| | - Yi Bai
- Department of Liver Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100730, China
| | - Jun-Yu Long
- Department of Liver Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100730, China
| | - Xiao-Bo Yang
- Department of Liver Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100730, China
| | - Samuel Seery
- Department of Humanities, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100730, China
| | - Hai-Tao Zhao
- Department of Liver Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100730, China
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D'Angelo A, Sobhani N, Bagby S, Casadei-Gardini A, Roviello G. Cabozantinib as a second-line treatment option in hepatocellular carcinoma. Expert Rev Clin Pharmacol 2020; 13:623-629. [PMID: 32394749 DOI: 10.1080/17512433.2020.1767591] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/11/2020] [Accepted: 05/07/2020] [Indexed: 01/06/2023]
Abstract
INTRODUCTION Hepatocellular carcinoma (HCC) is one of the most frequent tumors affecting the gastrointestinal tract and a universal cause of morbidity and mortality. Cabozantinib is a strong multi-inhibitor of receptor tyrosine kinases approved for renal cell carcinoma that could be useful also for the treatment of HCC. AREAS COVERED This review describes the chemical structure, the pharmacologic properties and current knowledge of the efficacy of cabozantinib in the treatment of HCC based on data available from first phase and later phase clinical trials. The ongoing studies testing cabozantinib, either alone or in combination with other drugs, are also described. EXPERT OPINION Despite the recent achievements in the use of cabozantinib for patients diagnosed with hepatocellular carcinoma, data are still needed to allow clinicians to make better decisions on how to treat specific patient subgroups.
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Affiliation(s)
- Alberto D'Angelo
- Department of Biology and Biochemistry, University of Bath , Bath, UK
| | - Navid Sobhani
- Department of Medicine, Baylor College , Houston, TX, USA
| | - Stefan Bagby
- Department of Biology and Biochemistry, University of Bath , Bath, UK
| | - Andrea Casadei-Gardini
- Division of Oncology, Department of Medical and Surgical Sciences for Children & Adults, University-Hospital of Modena and Reggio Emilia , Modena, Italy
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Casadei-Gardini A, Dadduzio V, Rovesti G, Cabibbo G, Vukotic R, Rizzato MD, Orsi G, Rossi M, Guarneri V, Lonardi S, D'agostino D, Celsa C, Andreone P, Zagonel V, Scartozzi M, Cascinu S, Cucchetti A. Utility of neutrophil-to-lymphocyte ratio to identify long-term survivors among HCC patients treated with sorafenib. Medicine (Baltimore) 2020; 99:e19958. [PMID: 32481366 DOI: 10.1097/md.0000000000019958] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/12/2022] Open
Abstract
Sorafenib is the first multikinase inhibitor demonstrating a survival benefit for patients suffering from advanced hepatocellular carcinoma (HCC). However, 1 issue remains open: what is the factor able to predict which patients will be long survivors?In the present study, we harnessed the potential of conditional survival, aiming at estimating the probability that a patient receiving sorafenib survives for more than 3 years.The present multicentric study was conducted on a cohort of 438 HCC patients. The primary end point was conditional overall survival. Kaplan-Meier survival analysis was used to calculate conditional overall survival probabilities at 3 years.The 3-year conditional survival of patients without disease progression highlights that NLR and ECOG are the factors that most accurately predict the probability of long survival. The 3-year conditional survival of patients with disease progression showed a medium effect size for HCV status, alpha-fetoprotein and NLR at all time-points. Macro-vascular portal vein invasion, extra hepatic disease, and BCLC we have a large effect size at 6 months and a medium effect size at 12 and 24 months.Our findings support the use of baseline NLR for the identification of patients with a higher probability of long-survival. NLR should be used as a stratification factor in the forthcoming clinical trials on the drugs for the advanced HCC now in pipeline.
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Affiliation(s)
- Andrea Casadei-Gardini
- Unit of Oncology, Department of Oncology, University Hospital of Modena and Reggio Emilia, Modena
| | | | - Giulia Rovesti
- Unit of Oncology, Department of Oncology, University Hospital of Modena and Reggio Emilia, Modena
| | - Giuseppe Cabibbo
- Section of Gastroenterology and Hepatology, Dipartimento di Promozione della Salute, Materno Infantile, Medicina Interna e Specialistica di Eccellenza (PROMISE), University of Palermo
| | - Ranka Vukotic
- Hepatology Unit, AOU Policlinico di Sant'Orsola and University of Bologna, Bologna
| | - Mario Domenico Rizzato
- Medical Oncology Unit 1, Istituto Oncologico Veneto IRCCS, Padova
- Unit of Surgery, Oncology and Gastroenterology, University of Padova, Padua
| | - Giulia Orsi
- Unit of Oncology, Department of Oncology, University Hospital of Modena and Reggio Emilia, Modena
| | - Margherita Rossi
- Section of Gastroenterology and Hepatology, Dipartimento di Promozione della Salute, Materno Infantile, Medicina Interna e Specialistica di Eccellenza (PROMISE), University of Palermo
| | - Valeria Guarneri
- Hepatology Unit, AOU Policlinico di Sant'Orsola and University of Bologna, Bologna
| | - Sara Lonardi
- Medical Oncology Unit 1, Istituto Oncologico Veneto IRCCS, Padova
| | - Dario D'agostino
- Section of Gastroenterology and Hepatology, Dipartimento di Promozione della Salute, Materno Infantile, Medicina Interna e Specialistica di Eccellenza (PROMISE), University of Palermo
| | - Ciro Celsa
- Section of Gastroenterology and Hepatology, Dipartimento di Promozione della Salute, Materno Infantile, Medicina Interna e Specialistica di Eccellenza (PROMISE), University of Palermo
| | - Pietro Andreone
- Hepatology Unit, AOU Policlinico di Sant'Orsola and University of Bologna, Bologna
- Division of Internal and Metabolic Medicine, AOU Modena and University of Modena e Reggio Emilia, Modena
| | | | - Mario Scartozzi
- Department of Medical Oncology, University of Cagliari, Cagliari, Italy
| | - Stefano Cascinu
- Unit of Oncology, Department of Oncology, University Hospital of Modena and Reggio Emilia, Modena
| | - Alessandro Cucchetti
- Department of Molecular and Clinical Cancer Medicine, University of Liverpool, Liverpool, UK
- Department of Medical and Surgical Sciences-DIMEC, Alma Mater Studiorum-University of Bologna, Bologna
- General Surgery, Morgagni-Pierantoni Hospital, Forlì, FC, Italy
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27
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Casadei-Gardini A, Orsi G, Caputo F, Ercolani G. Developments in predictive biomarkers for hepatocellular carcinoma therapy. Expert Rev Anticancer Ther 2020; 20:63-74. [PMID: 31910040 DOI: 10.1080/14737140.2020.1712198] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
Introduction: Hepatocellular carcinoma (HCC) is the most common primary tumor of the liver and the third largest cause of cancer-relateddeaths worldwide. Potentially curative treatments (surgical resection, radiofrequency or liver transplantation) are only available for few patients, while transarterial chemoembolization (TACE) or systemic agents are the best treatments for intermediate and advanced stage disease. The identification of markers that allow us to choose the best treatment for the patient is urgent.Areas covered: In this review we summarize the potential biological markers to predict the efficacy of all treatment available in patients with HCC and discuss anew biomarker with ahigher potential of success in the next future.Expert opinion: HCC is aheterogeneous disease. Tumors are heterogeneous in terms of genetic alteration,with spatial heterogeneity in cellular density, necrosis and angiogenesis.This heterogeneity may affect prognosis and treatment. Tumor heterogeneity can be difficult to quantify with traditional imaging due to subjective assessment of images; the same for sampling biopsy, which evaluates only asmall part of the tumor. We think that combining multi-OMICSwith radiomics represents apromising strategy for evaluating tumor heterogenicity and for identifying biomarkers of response and prognosis.
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Affiliation(s)
- Andrea Casadei-Gardini
- Division of Oncology, Department of Medical and Surgical Sciences for Children & Adults, University-Hospital of Modena and Reggio Emilia, Modena, Italy
| | - Giulia Orsi
- Division of Oncology, Department of Medical and Surgical Sciences for Children & Adults, University-Hospital of Modena and Reggio Emilia, Modena, Italy
| | - Francesco Caputo
- Division of Oncology, Department of Medical and Surgical Sciences for Children & Adults, University-Hospital of Modena and Reggio Emilia, Modena, Italy
| | - Giorgio Ercolani
- General and Oncology Surgery, Morgagni-Pierantoni Hospital, Forli, Italy.,Department of Medical & Surgical Sciences-DIMEC, Alma Mater Studiorum-University of Bologna, Bologna, Italy
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Sun H, Feng F, Xie H, Li X, Jiang Q, Chai Y, Wang Z, Yang R, Li R, Hou J. Quantitative examination of the inhibitory activation of molecular targeting agents in hepatocellular carcinoma patient-derived cell invasion via a novel in vivo tumor model. Animal Model Exp Med 2019; 2:259-268. [PMID: 31942558 PMCID: PMC6930997 DOI: 10.1002/ame2.12085] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/06/2019] [Revised: 08/31/2019] [Accepted: 09/03/2019] [Indexed: 12/24/2022] Open
Abstract
BACKGROUND The outcomes for patients with advanced hepatocellular carcinoma (HCC) receiving sorafenib are far from satisfactory because of treatment resistance to sorafenib. However, the exact mechanism of resistance to sorafenib remains unclear and it is valuable to establish a novel mouse model to quantitatively analyze the inhibition rates of sorafenib on the invasive growth of HCC cells in the liver. METHODS HCC tissue microblocks derived from patients were cultured and mixed with hydrogel drops. Then, hydrogel drops containing microblocks of HCC tissue were attached onto the surface of the livers of nude mice to form lesions or nodules of HCC. The mice received molecular targeting agents through oral administration. Livers with tumor nodules were harvested for H&E staining (hematoxylin-eosin staining) analysis and H&E staining images were quantitatively analyzed using image J software. The invasive growth of HCC cells into the liver was calculated using the depth of the lesions compared with the total thickness of the liver. RESULTS Microblocks containing cells derived from HCC patients can form lesions in the liver of nude mice. Oral administration of molecular targeting agents inhibited the invasive growth of HCC cells in the liver of nude mice. CONCLUSIONS The model established in this study involves the invasive growth of HCC cells in the liver of nude mice, and the model allows for the quantitative analysis of the inhibitory effect of molecular targeting agents on the invasion of HCC cells in vivo.
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Affiliation(s)
- Huiwei Sun
- Research Center for Clinical and Translational MedicineThe Fifth Medical CenterGeneral Hospital of Chinese PLABeijingChina
| | - Fan Feng
- Research Center for Clinical and Translational MedicineThe Fifth Medical CenterGeneral Hospital of Chinese PLABeijingChina
- Center for Clinical LaboratoryThe Fifth Medical CenterGeneral Hospital of Chinese PLABeijingChina
| | - Hui Xie
- Department of Interventional TherapyThe Fifth Medical CenterGeneral Hospital of Chinese PLABeijingChina
| | - Xiaojuan Li
- Research Center for Clinical and Translational MedicineThe Fifth Medical CenterGeneral Hospital of Chinese PLABeijingChina
- Medical School of Chinese PLABeijingChina
| | - Qiyu Jiang
- Research Center for Clinical and Translational MedicineThe Fifth Medical CenterGeneral Hospital of Chinese PLABeijingChina
| | - Yantao Chai
- Research Center for Clinical and Translational MedicineThe Fifth Medical CenterGeneral Hospital of Chinese PLABeijingChina
| | - Zhijie Wang
- Research Center for Clinical and Translational MedicineThe Fifth Medical CenterGeneral Hospital of Chinese PLABeijingChina
| | - Ruichuang Yang
- Research Center for Clinical and Translational MedicineThe Fifth Medical CenterGeneral Hospital of Chinese PLABeijingChina
| | - Ruisheng Li
- Research Center for Clinical and Translational MedicineThe Fifth Medical CenterGeneral Hospital of Chinese PLABeijingChina
| | - Jun Hou
- Research Center for Clinical and Translational MedicineThe Fifth Medical CenterGeneral Hospital of Chinese PLABeijingChina
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Rovesti G, Orsi G, Kalliopi A, Vivaldi C, Marisi G, Faloppi L, Foschi FG, Silvestris N, Pecora I, Aprile G, Molinaro E, Riggi L, Ulivi P, Canale M, Cucchetti A, Tamburini E, Ercolani G, Fornaro L, Andreone P, Zavattari P, Scartozzi M, Cascinu S, Casadei-Gardini A. Impact of Baseline Characteristics on the Overall Survival of HCC Patients Treated with Sorafenib: Ten Years of Experience. Gastrointest Tumors 2019; 6:92-107. [PMID: 31768353 DOI: 10.1159/000502714] [Citation(s) in RCA: 28] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/05/2019] [Accepted: 07/29/2019] [Indexed: 12/24/2022] Open
Abstract
Background Sorafenib has been established as the standard of care for patients with advanced hepatocellular carcinoma (HCC) since 2007 on the basis of two landmark trials (SHARP and Asia-Pacific). Ten years have passed since then and, despite much research in the field, still no validated real-life prognostic markers are available for HCC patients treated with this drug. Therefore, going through 10 years of research into sorafenib of several Italian Cancer Centers, we conducted a field-practice study aimed at identifying baseline clinical factors that could be significantly associated with overall survival (OS). Method Univariate/multivariate analyses were conducted to retrospectively identify the impact of baseline characteristics on the OS of 398 advanced HCC patients treated with sorafenib. Results Based on univariate analysis, α-fetoprotein (AFP), albumin, AST, bilirubin, Child-Pugh, ECOG, systemic immune-inflammation index (SII), albumin-bilirubin (ALBI) grade, and portal vein thrombosis were significantly associated with shorter OS. Following adjustment for clinical covariates positive in univariate analysis, the multivariate analysis including AFP, age, etiology, albumin, aspartate transaminase (AST), bilirubin, Child-Pugh, LDH, platelet-to-lymphocyte ratio, ECOG, ALBI grade, portal vein thrombosis, SII, and BCLC stage identified increase in LDH, age >70 years, no viral etiologies, ECOG >0, albumin <35, ALBI grade 2, and AST >40 as prognostic factors for poorer OS based on the 5% significance level. Conclusion Our study highlights that baseline hepatic function, patient-centered variables, and etiology have prognostic value. These findings might have implications in terms of therapeutic decision-making and patient counseling.
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Affiliation(s)
- Giulia Rovesti
- Division of Oncology, Department of Oncology and Hematology, University Hospital of Modena, Modena, Italy
| | - Giulia Orsi
- Division of Oncology, Department of Oncology and Hematology, University Hospital of Modena, Modena, Italy
| | - Andrikou Kalliopi
- Division of Oncology, Department of Oncology and Hematology, University Hospital of Modena, Modena, Italy
| | - Caterina Vivaldi
- Department of Medical Oncology, Pisa University Hospital, Pisa, Italy
| | - Giorgia Marisi
- Biosciences Laboratory, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Meldola, Italy
| | - Luca Faloppi
- Oncology Unit, Macerata Hospital, Macerata, Italy
| | | | | | - Irene Pecora
- Department of Medical Oncology, Pisa University Hospital, Pisa, Italy
| | | | - Eleonora Molinaro
- Division of Oncology, Department of Oncology and Hematology, University Hospital of Modena, Modena, Italy
| | - Laura Riggi
- Division of Oncology, Department of Oncology and Hematology, University Hospital of Modena, Modena, Italy
| | - Paola Ulivi
- Biosciences Laboratory, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Meldola, Italy
| | - Matteo Canale
- Biosciences Laboratory, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Meldola, Italy
| | - Alessandro Cucchetti
- Department of Medical and Surgical Sciences-DIMEC, S. Orsola-Malpighi Hospital, Alma Mater Studiorum-University of Bologna, Bologna, Italy.,General Surgery, Morgagni-Pierantoni Hospital, Forlì, Italy
| | | | - Giorgio Ercolani
- Medical Oncology Unit, Hospital of Vicenza, Vicenza, Italy.,Department of Medical and Surgical Sciences-DIMEC, S. Orsola-Malpighi Hospital, Alma Mater Studiorum-University of Bologna, Bologna, Italy
| | - Lorenzo Fornaro
- Department of Medical Oncology, Pisa University Hospital, Pisa, Italy
| | - Pietro Andreone
- Division of Internal and Metabolic Medicine, Baggiovara Hospital, University of Modena and Reggio Emilia, Modena, Italy
| | - Patrizia Zavattari
- Unit of Biology and Genetics, Department of Biomedical Sciences, University of Cagliari, Cagliari, Italy
| | - Mario Scartozzi
- Department of Medical Sciences and Public Health, University of Cagliari, Cagliari, Italy
| | - Stefano Cascinu
- Department of Medical Oncology, Università Vita-Salute, San Raffaele Hospital IRCCS, Milan, Italy
| | - Andrea Casadei-Gardini
- Division of Oncology, Department of Oncology and Hematology, University Hospital of Modena, Modena, Italy
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