Salvage systemic therapy for advanced gastric and oesophago‐gastric junction adenocarcinoma

Background Salvage systemic therapy has become the new standard of care in patients with advanced gastric and oesophago‐gastric junction (OGJ) adenocarcinoma, following disease progression on first‐line fluoropyrimidine and platinum‐containing chemotherapy. Pharmacological agents proven to be effective in this setting include both chemotherapy and biological therapy, however, the consensus on the best salvage systemic therapy has not been reached. Objectives To assess the effects of systemic chemotherapy and biological therapy, either alone or in combination, on overall survival (OS) and progression‐free survival (PFS) in patients with advanced gastric and OGJ adenocarcinoma, whose disease has progressed on, or relapsed after first‐line fluoropyrimidine and platinum‐containing chemotherapy. Adverse events (AEs), tumour response rate (TRR) and quality of life (QoL) associated with systemic chemotherapy and/or biological therapy were additionally assessed. Search methods We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, trial registries and proceedings of the major oncology conferences up to October 2020. We additionally handsearched the reference lists of studies. No language restriction was applied. Selection criteria We included randomised controlled trials (RCTs) comparing salvage systemic therapy (chemotherapy and/or biological therapy) and either another type of salvage systemic therapy, placebo, best supportive care (BSC) or no treatment in patients with gastric and OGJ adenocarcinoma refractory to first‐line fluoropyrimidine and platinum‐containing chemotherapy. Data collection and analysis Two review authors independently performed selection of eligible studies and the primary author extracted study characteristics and outcome data from included studies. We assessed the quality and risk of bias of eligible studies according to the Cochrane Handbook for Systematic Reviews of Interventions. We expressed pooled estimates of effect using hazard ratio (HR) calculated using an inverse variance random‐effects model for time‐to‐event data, and risk ratio (RR) calculated using Mantel‐Haenszel random‐effects model for binary data. The certainty of evidence was graded using GRADEpro. Main results We identified 17 RCTs with 5110 participants for inclusion in this review. Tweenty‐nine studies are ongoing and twenty studies are awaiting classification. No studies examined the following comparisons: chemotherapy combined wi