Immune checkpoint inhibitors (ICIs) have transformed the therapeutic landscape for several malignancies, but their efficacy in unresectable pancreatic adenocarcinoma remains uncertain. This systematic review aimed to evaluate the effectiveness and safety of ICIs in this context, focusing on overall survival (OS), progression-free survival (PFS), objective response rate (ORR), disease control rate (DCR), and toxicity. A comprehensive search of MEDLINE, EMBASE, CENTRAL, and Scopus identified 34 eligible studies, including randomized controlled trials and observational cohorts. Quantitative synthesis involved 21 studies comprising 937 patients, with additional qualitative analyses on biomarker-driven subgroups and early-phase trials. The median OS across studies was 8.65 months, while the median PFS was 2.55 months. The ORR and DCR were 16.2% and 50.3%, respectively, with grade ≥3 treatment-related adverse events occurring in 22% of patients. Promising outcomes were observed in MSI-H/dMMR populations, although these represented only 1-2% of cases. Combination strategies with chemotherapy demonstrated synergistic potential but lacked definitive evidence due to heterogeneity and the absence of phase III trials. ICIs showed a manageable toxicity profile, highlighting their feasibility in selected patients. Future research should focus on overcoming tumor microenvironment barriers and identifying biomarkers to optimize responsiveness and expand the applicability of ICIs in pancreatic cancer.

Pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive cancer with poor prognosis. When it metastasizes to the liver, treatment options become particularly limited and challenging. Current treatment options for liver metastatic PDAC are limited, and chemotherapy alone often proves insufficient. Immunotherapy, particularly programmed cell death 1 (PD-1) inhibitors like sintilimab, shows potential efficacy for various cancers but has limited reports on PDAC. This study compares the efficacy and safety of sintilimab plus S-1 and gemcitabine vs S-1 and gemcitabine alone in liver metastatic PDAC.

To explore the feasibility and effectiveness of combined PD-1 inhibitor sintilimab and S-1 and gemcitabine (combination group) vs S-1 and gemcitabine used alone (chemotherapy group) for treating liver metastatic pancreatic adenocarcinoma.

Eligible patients were those with only liver metastatic PDAC, an Eastern Cooperative Oncology Group performance status of 0-1, adequate organ and marrow functions, and no prior anticancer therapy. Participants in the combination group received intravenous sintilimab 200 mg every 3 weeks, oral S-1 40 mg/m² twice daily on days 1-14 of a 21-day cycle, and intravenous gemcitabine 1000 mg/m² on days 1 and 8 of the same cycle for up to eight cycles or until disease progression, death, or unacceptable toxicity. Participants in the chemotherapy group received oral S-1 40 mg/m² twice daily on days 1-14 of a 21-day cycle and intravenous gemcitabine 1000 mg/m² on days 1 and 8 of the same cycle for up to eight cycles. Between June 2020 and December 2021, 66 participants were enrolled, with 32 receiving the combination treatment and 34 receiving chemotherapy alone.

The group receiving the combined therapy exhibited a markedly prolonged median overall survival (18.8 months compared to 10.3 months, P < 0.05) and progression-free survival (9.6 months vs 5.4 months, P < 0.05). compared to the chemotherapy group. The incidence of severe adverse events did not differ significantly between the two groups (P > 0.05).

The combination of PD-1 inhibitor sintilimab with S-1 and gemcitabine demonstrated effectiveness and safety for treating liver metastatic PDAC, meriting further investigation.

Pancreatic adenocarcinoma, a malignancy that arises in the cells of the pancreas, is a devastating disease with unclear etiology and often poor prognosis. Locally advanced pancreatic cancer, a stage where the tumor has grown significantly but has not yet spread to distant organs, presents unique challenges in treatment. This article aims to discuss the current strategies, challenges, and future directions in the management of locally advanced pancreatic adenocarcinoma (LAPC).

To investigate the feasibility and efficacy of programmed cell death 1 (PD-1) inhibitor sintilimab plus concurrent chemoradiotherapy for LAPC.

Eligible patients had LAPC, an Eastern cooperative oncology group performance status of 0 or 1, adequate organ and marrow functions, and no prior anticancer therapy. In the observation group, participants received intravenous sintilimab 200 mg once every 3 wk, and received concurrent chemoradiotherapy (concurrent conventional fractionated radiotherapy with doses planning target volume 50.4 Gy and gross tumor volume 60 Gy in 28 fractions and oral S-1 40 mg/m2 twice daily on days 1-14 of a 21-d cycle and intravenous gemcitabine 1000 mg/m2 on days 1 and 8 of a 21-d cycle for eight cycles until disease progression, death, or unacceptable toxicity). In the control group, participants only received concurrent chemoradiotherapy. From April 2020 to November 2021, 64 participants were finally enrolled with 34 in the observation group and 30 in the control group.

Thirty-four patients completed the scheduled course of chemoradiotherapy, while 32 (94.1%) received sintilimab plus concurrent chemoradiotherapy with 2 patients discontinuing sintilimab in the observation group. Thirty patients completed the scheduled course of chemoradiotherapy in the control group. Based on the Response Evaluation Criteria in Solid Tumors guidelines, the analysis of the observation group revealed that a partial response was observed in 11 patients (32.4%), stable disease was evident in 19 patients (55.9%), and 4 patients (11.8%) experienced progressive disease; a partial response was observed in 6 (20.0%) patients, stable disease in 18 (60%), and progressive disease in 6 (20%) in the control group. The major toxic effects were leukopenia and nausea. The incidence of severe adverse events (AEs) (grade 3 or 4) was 26.5% (9/34) in the observation group and 23.3% (7/30) in the control group. There were no treatment-related deaths. The observation group demonstrated a significantly longer median overall survival (22.1 mo compared to 15.8 mo) (P < 0.05) and progression-free survival (12.2 mo vs 10.1 mo) (P < 0.05) in comparison to the control group. The occurrence of severe AEs did not exhibit a statistically significant difference between the observation group and the control group (P > 0.05).

Sintilimab plus concurrent chemoradiotherapy was effective and safe for LAPC patients, and warrants further investigation.

While combined immunotherapy and anti-angiogenic therapy have demonstrated efficacy in renal cell carcinoma, non-small cell lung cancer and hepatocellular carcinoma, the efficacy of first-line treatment for pancreatic ductal adenocarcinoma (PDAC) with germline BRCA2 mutation remains unproven. We described a BRCA2-mutated patient with PDAC who presented with posterior cardiac metastasis 8 months after surgery. After receiving four cycles of anlotinib combined with tislelizumab, abdominal CT scans indicated a complete response. The patient sustained this response for over 14 months on the combination regimen, with no reported adverse events. In conclusion, the combination of tislelizumab and anlotinib may offer a viable therapeutic option for recurrent metastatic BRCA2-mutated PDAC.

Paclitaxel-based chemotherapy represented by nanoparticle albumin-bound paclitaxel (nab-ptx) combined with programmed cell death protein 1 (PD-1)/programmed death ligand 1 (PD-L1) inhibitors has become the standard model for the 1st treatment of advanced non-small cell lung cancer (NSCLC) with negative driver genes (such as EGFR, ALK, etc.), indicating that nab-ptx and PD-1/PD-L1 inhibitors are synergistic. Considering PD-1/PD-L1 inhibitors alone or chemotherapy single has limited efficiency in the 2nd line or above of NSCLC, so it is of great significance to explore the combination of PD-1/PD-L1 inhibitors and nab-ptx to further improve the therapeutic efficiency in such field.

We retrospectively collected the date of these advanced NSCLC patients who accept the combination treatment of PD-1/PD-L1 inhibitor and nab-ptx in the 2nd or above line. We further analysed baseline clinical characteristics, therapeutic efficacy, treatment-related adverse events (AEs) and followed up survival. The main parameters of the study were objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS), overall survival (OS) and AEs.

A total of 53 patients were enrolled in this study. The preliminary results indicated that the ORR of the combination of camrelizumab and nab-ptx was about 36% in the 2nd or above line of NSCLC, with 19 cases of partial response (PR), 16 of stable disease (SD), and 18 cases of progressive disease (PD); the mean PFS and OS were 5 months and 10 months, respectively. Further subgroup analysis demonstrated that the expression of PD-L1 level and the decrease of regulatory T cell (Treg) correlated with the efficiency. the main adverse reactions were neuropathy, bone marrow suppression, fatigue, and hypothyroidism, most of which were mild and tolerable, indicating such regimen was higher efficiency and lower cytotoxicity for NSCLC.

The combination of nab-ptx and camrelizumab shows promising efficiency and lower toxicities for advanced NSCLC in the 2nd or above line treatment. The mechanism of action may be related to depleting Treg ratio; such a regimen may have the potential to become an effective treatment approach for NSCLC. However, due to the limitation of sample size, the real value of this regimen needs to be further confirmed in the future.