Treatment options for senior gastric cancer patients (aged ≥60 years): a worldwide network meta-analysis

Disease burden of gastric cancer among senior population could not be neglected. Nevertheless, there were lacking of systemic evidences regarding specified treatments. We aimed to conduct the first network meta-analysis on this topic.

From inception to August 2025, PubMed, Web of Science, Embase, Cochrane Central and ASCO meeting library were searched for literature retrieval. Randomized controlled trials investigating relative survival outcomes of different regimens among senior gastric cancer patients were included. Risk of bias 2 (ROB2) tool was employed to assess methodological quality. Hazard ratio with 95% confidence interval was used as effect size. Overall survival was primary endpoint while event-free or progression-free survival was secondary endpoint. R software was applied to perform Bayesian network meta-analysis.

120 trials were eligible, including at least 21 393 senior patients. Only one trial was rated as high risk of bias. Regarding resectable gastric cancer, pDuFLOT (EFS 0.43, 0.22-0.84) and pSOX (EFS 0.49, 0.31-0.76) significantly improved survival outcomes than aCAPOX. Concerning first-line regimens, CadCAPOX (OS 0.65, 0.47-0.90), SuCAPOX (OS 0.68, 0.50-0.93), PemCAPOX (OS 0.77, 0.64-0.92) and NiCAPOX (OS 0.75, 0.63-0.89) showed significantly better survival than CAPOX. Subgroup analyses on regions, HER2, PD-L1 and CLDN18.2 expression levels were also performed. Moreover, first-line maintenance, second-line, third-line or subsequent regimens among senior patients were also meta-analyzed.

pDuFLOT and pSOX are potential regimens among senior patients with resectable gastric cancer. At this moment, pDuFLOT may be globally used while pSOX should better be applied among East Asian countries. CadCAPOX, SuCAPOX, PemCAPOX and NiCAPOX are considered as potential first-line regimens among HER2-negative senior patients. CadCAPOX and SuCAPOX are probably more fit for East Asian patients currently, while NiCAPOX may be better applied among Western countries and PemCAPOX has the potential of worldwide application. SuCAPOX is a potential regimen among HER2-negative/PD-L1-positive senior patients, while PemCAPOX may also be considered. Currently, standard CAPOX or FOLFOX regimen may still be available for HER2-negative senior patients with CLDN18.2, FGFR2b or MET positivity. Meanwhile, among HER2-positive senior patients, TraCAPOX is still considered to be available. Regarding first-line maintenance treatments, RamP is a potential regimen among HER2-negative or non-specific senior patients, especially those from Western countries. As second-line regimens, FruP and RamP may be potentially available among East Asian and worldwide HER2-negative senior patients respectively, while T-DXd has the potential of global application among HER2-positive counterparts. Concerning third-line or subsequent regimens, T-DXd is potentially available among HER2-positive senior patients, especially from East Asian countries. Among HER2-negative or non-specific patients, RamIRI is a potential regimen, especially among East Asian patients, while nivolumab and regorafenib may still be available at this moment. Meanwhile, nivolumab and other parallel regimens already recommended by guidelines are still potentially available among HER2-negative/CLDN18.2-positive senior patients. As the first network meta-analysis on this topic, our conclusions may not only provide potential supplements for current guidelines, but also reveal the necessity and directions for future clinical and mechanism researches, especially because of the underpowered subgroup data and exploratory nature of regional applicability.