Immune checkpoint inhibitors with trastuzumab and chemotherapy in advanced HER2-positive gastric cancer: A systematic review and meta-analysis

Abstract

Background: Gastric and gastroesophageal junction (GEJ) cancers with HER2 overexpression have limited durable responses to standard HER2-targeted therapies. Adding immune checkpoint inhibitors (ICIs) to anti-HER2 regimens has emerged as a promising strategy to enhance treatment efficacy. This study assessed the efficacy and safety of combining ICIs with trastuzumab therapy in patients with HER2-positive gastric or GEJ adenocarcinoma.

Methods: A systematic review and meta-analysis was conducted according to PRISMA guidelines. Eligible studies included patients with HER2-positive gastric or GEJ cancer treated with chemotherapy inhibitors plus trastuzumab therapy, with or without PD-1/PD-L1. Statistical analyses were performed using the "meta" and "IPDfromKM" packages in R version 4.4.2.

Results: From 1306 records, five studies involving 993 patients were included. Combination therapy significantly improved OS (HR, 0.73; 95 % CI, 0.64-0.84; p < .0001); PFS (HR, 0.69; 95 % CI, 0.60-0.80; p < .0001); ORR (OR, 1.95; p < .0001) and DCR (OR, 2.94; p = .009) also favored combination therapy. In the combination therapy, although with insignificant results, patients with CPS≥ 1 showed a tendency to better OS (HR: 0.88; 95 % CI, 0.52-1.49; p = .58) and PFS (HR: 0.82; 95 % CI, 0.48-1.42; p = 0.4). Hypothyroidism was more frequent with combination therapy (RR, 3.24; p = .008), while other 11 AEs showed no difference between groups.

Conclusions: ICIs plus trastuzumab therapy improve survival and response in advanced HER2-positive gastric or GEJ cancer, particularly in PD-L1-positive and first-line settings, with manageable toxicity.

Keywords: Combination therapy; Gastric cancer; HER2-targeted therapy; Immune checkpoint inhibitors; Meta-analysis.