Abstract
BackgroundImmunotherapy dramatically changed the treatment landscape of gastric cancer in recent years. PD-L1 expression was proposed as a biomarker; however, the treatment strategy according to PD-L1 is still uncertain. Here, we aimed to find the appropriate cutoff value of PD-L1 expression for gastric cancer immunotherapy.MethodsWe did a systematic electronic research of prospective clinical trials of gastric cancer immunotherapy across databases. Studies that provided subgroup analysis results stratified by PD-L1 expression were included. Objective response rate (ORR), disease control rate (DCR), hazard ratio (HR), and 95% confidential interval (CI) of progression-free survival (PFS) and overall survival (OS) at different PD-L1 cutoff values were extracted.ResultsTwelve studies and 6,488 patients in total were finally included for pooled analysis. ORR in allover, PD-L1-negative, combined positive score (CPS) ≥1, CPS ≥5, and CPS ≥10 population was 10%, 3%, 13%, 20%, and 23%, respectively. Immune checkpoint inhibitor (ICI) monotherapy failed to show survival advantage in allover and PD-L1-negative patients. Single-agent ICI therapy prolonged OS (HR = 0.84, 95% CI: 0.74–0.96) but not PFS (HR = 1.38, 95% CI: 0.91–2.09) in PD-L1 CPS ≥1 patients. For combined immunotherapy, ORR in allover, PD-L1-negative, CPS ≥1, CPS ≥5, and CPS ≥10 population was 64%, 57%, 48%, 60%, and 58%, respectively. Allover population could gain survival benefit from combined immunotherapy based on the results from Checkmate-649. OS (HR = 0.81, 95% CI: 0.71–0.92) and PFS (HR = 0.77, 95% CI: 0.69–0.86) were significantly prolonged in PD-L1 CPS ≥1 patients receiving combined immunotherapy.ConclusionEfficacy and survival advantages improved with PD-L1 CPS. CPS ≥1 was the cutoff value for ICI monotherapy to gain survival benefit. Combined immunotherapy prolonged PFS and OS in allover population but needs further study to confirm it.
Highlights
Programmed death protein-1/ligand 1 (PD-1/PD-L1) inhibitors profoundly changed the treatment landscape of gastric cancer in recent years
Studies were included if they met the following inclusion criteria: 1) randomized or nonrandomized clinical trials that reported the efficacy or survival outcomes of PD-1/PD-L1 inhibitors or immune checkpoint inhibitor (ICI) plus chemotherapy for gastric cancer; and 2) studies that provided the results stratified by PD-L1 Combined positive score (CPS)
Following the publication of several clinical trials, immunotherapy transformed the treatment of gastric cancer, and PD-L1 has been proposed as a biomarker for gastric cancer immunotherapy
Summary
Programmed death protein-1/ligand 1 (PD-1/PD-L1) inhibitors profoundly changed the treatment landscape of gastric cancer in recent years. PD-L1 expression has been proposed as one of the pan-cancer biomarkers for immunotherapy. In KEYNOTE-059, pembrolizumab exhibited favorable efficacy in gastric cancer, especially in PD-L1-positive patients, with an objective response rate (ORR) of 15.5% and duration of response (DOR) of 16.3 months [2]. Pembrolizumab was approved for PD-L1-positive gastric cancer patients in second- or later-line treatment by the Food and Drug Administration (FDA). Pembrolizumab failed to show superiority to paclitaxel in second-line gastric cancer treatment in KEYNOTE-061, posthoc analysis revealed that the treatment effect was greater in patients with a PD-L1 CPS ≥10 than CPS ≥1 [4]. Immunotherapy dramatically changed the treatment landscape of gastric cancer in recent years. We aimed to find the appropriate cutoff value of PD-L1 expression for gastric cancer immunotherapy
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