Immunotherapy or targeted therapy versus best supportive care for advanced gastric cancer: a systematic review and meta-analysis of randomized trials

Abstract

Purpose To assess the efficacy and safety of non-chemotherapy anticancer drugs (ACDs) compared to best supportive care (BSC) or placebo for the treatment of advanced gastric cancer (GC). Methods Systematic review of randomized controlled trials (RCTs) searching (May 2022) MEDLINE, EMBASE, CENTRAL, Epistemonikos, ClinicalTrials.gov and PROSPERO. Certainty of evidence was evaluated following GRADE. Results Six RCTs included. Targeted therapies likely result in a slight increase in overall survival (OS) (HR 0.84, 95%CI 0.75, 0.93; moderate certainty) and progression free survival (PFS) (HR 0.52, 95%CI 0.43, 0.62; moderate certainty). Toxicity had a slightly increased risk (RR 1.19, 95%CI 0.95, 1.48; low certainty). Immunotherapy also showed a likely improvement in PFS (HR 0.60, 95%CI 0.49, 0.73; moderate certainty) while toxicity showed a likely higher risk (RR 2.72, 95% CI 1.24, 5.94; moderate certainty). However, benefits in survival translated to time gains slightly over a month for OS and less than a month for PFS. No data were reported on performance status (PS), hospital admissions, or quality of life (QoL). Conclusions Our study suggests some survival benefits with low toxicity from these treatments, but gains are marginal. Uncertainties persist regarding their impact on QoL and outcomes for patients with poor PS. Caution is advised in treatment selection for advanced patients, who should actively participate in decision-making. Future research should include diverse patient populations and assess patient-centered outcomes with consistent comparator groups for BSC. Registration The study protocol was registered in OSF (https://doi.org/10.17605/OSF.IO/7CHX6) on 2022-04-01.