Efficacy and Safety of Anti-PD1/PDL1 in Advanced Biliary Tract Cancer: A Systematic Review and Meta-Analysis

Abstract

BackgroundAnti-programmed cell death protein 1 and its ligand (anti-PD1/PDL1) have been proposed as a promising therapeutic option for advanced biliary tract cancer (aBTC). Given the scarce quantitative analyses of anti-PD1/PDL1 in aBTC, we thus did a meta-analysis to assess the benefits and risks of this emerging treatment strategy in patients with aBTC.MethodsPubMed, Embase, the Cochrane Library, Web of Science, and meeting resources were searched for relevant studies. The main endpoints were median progression-free survival (mPFS), median overall survival (mOS), objective response rate (ORR), disease control rate (DCR), any-grade adverse events (AEs), and grade 3–4 AEs.ResultsTwenty-eight studies with 1,338 participants were included. The best curative effect was found in the anti-PD1/PDL1 combined with anti-CTLA4 and chemotherapy group (mPFS: 12.4 months; mOS: 16.0 months; ORR: 45.1%; DCR: 95.0%), followed by the anti-PD1/PDL1 plus chemotherapy group (mPFS: 8.2 months; mOS: 14.8 months; ORR: 36.3%; DCR: 84.6%), the anti-PD1/PDL1 plus antiangiogenesis group (mPFS: 4.9 months; mOS: 10.2 months; ORR: 17.5%; DCR: 68.7%), the anti-PD1/PDL1 plus anti-cytotoxic T lymphocyte antigen 4 (anti-CTLA4) group (mPFS: 2.9 months; mOS: 8.3 months; ORR: 9.9%; DCR: 36.8%), and the anti-PD1/PDL1 monotherapy group (mPFS: 2.5 months; mOS: 7.6 months; ORR: 6.8%; DCR: 34.7%). Compared with anti-PD1-containing regimens, anti-PDL1-containing regimens achieved preferable mPFS (11.1 vs. 3.8 months), mOS (12.2 vs. 9.8 months), and ORR (23.7% vs. 17.4%), despite a similar DCR (61.1% vs. 61.3%). The mPFS, mOS, ORR, and DCR were 10.6 months, 15.8 months, 42.3%, and 88.6% of first-line anti-PD1/PDL1 and 3.0 months, 9.1 months, 11.6%, and 51.1% of second-line therapy or beyond, respectively. There were 80.6% and 34.0% of the patients suffering any-grade AEs and grade 3–4 AEs. Anti-PD1/PDL1 monotherapy might be considered as a safer alternative than combination regimens. Meanwhile, obvious toxicities in the first-line setting could not be neglected.ConclusionsAnti-PD1/PDL1 showed encouraging efficacy and acceptable safety profile in aBTC and, thus, could be an alternative treatment.

Survival benefit and biomarker of PD‐1 inhibitor combination therapy in first‐line of advanced biliary tract cancer: A retrospective study

“…Similar to the findings of Zhu's study, early use of immunotherapy and chemotherapy combined with targeted therapy is recommended for patients who are able to tolerate it 24 . Additionally, a recent meta‐analysis of the efficacy of anti‐PD‐1/PD‐L1 in advanced BTC showed that median OS was longer in the first‐line settings than in the second‐line settings or beyond 25 …”

“…24 Additionally, a recent meta-analysis of the efficacy of anti-PD-1/PD-L1 in advanced BTC showed that median OS was longer in the first-line settings than in the second-line settings or beyond. 25 Peripheral blood inflammation scores have great potential in predicting the efficacy of immunotherapy and have been reported in a variety of tumors, such as hepatocellular carcinoma, 26 non-small cell lung cancer, 27 and pancreatic cancer. 28 Several studies have shown that inflammation scores can be used as a predictor of response to anti-PD-1 in patients with BTC.…”

“… 24 Additionally, a recent meta‐analysis of the efficacy of anti‐PD‐1/PD‐L1 in advanced BTC showed that median OS was longer in the first‐line settings than in the second‐line settings or beyond. 25 …”

Construction of a ferroptosis-related lncRNA signature for predicting prognosis, immune response and drug sensitivity in cervical squamous cell carcinoma and endocervical adenocarcinoma

“…Programmed cell death 1/programmed cell death ligand 1 (PD1/PDL1) enhances tumor resistance to immuneinduced apoptosis and promotes tumor growth. Targeting the PD1/PDL1 axis can effectively inhibit tumor progression and improve patients' OS [69][70][71][72][73][74][75][76][77][78]. We found that several immune cells and immunological checkpoints were differentially expressed in the two risk subgroups after performing immune cell infiltration and immune checkpoint analyses using the CESC prognostic model.…”

The predictive value of PD-L1 expression in response to anti-PD-1/PD-L1 therapy for biliary tract cancer: a systematic review and meta-analysis

“…Various drugs, including conventional chemotherapeutic agents, anti-angiogenic agents, and inhibitors targeting other immune checkpoints (e.g., cytotoxic T lymphocyte-4), have been introduced in combination regimens with anti-PD-1/PD-L1 agents for the treatment of BTC ( 27 , 28 , 30 , 37 ). A recent meta-analysis involving patients with BTC showed superior treatment response and clinical outcomes using combination regimens with anti-PD-1/PD-L1 therapy compared to anti-PD-1/PD-L1 monotherapy ( 58 ). This was consistent with our results, which demonstrated a higher response rate in combination therapy.…”