Apatinib plus S-1 for previously treated, advanced gastric or gastro-oesophageal junction adenocarcinoma: a phase 2, single-arm, prospective study.

Abstract

The current management of advanced gastric or gastro-oesophageal junction adenocarcinoma remains unsatisfactory. We investigated the efficacy and safety of the combination therapy of apatinib and S-1, considering the potential advantage of home-based treatment without hospital admission, in patients with platinum-refractory gastric or gastro-oesophageal junction adenocarcinoma. In this open-label, single-arm, phase 2 trial, in each 21-day cycle, eligible patients received apatinib at an initial dose of 500 mg once daily continuously and S-1 at a dose of 40-60 mg twice daily on days 1-14 until the trail was discontinued disease progression, development of intolerable toxicity, or withdrawal of consent. The primary endpoints were progression-free survival. The secondary endpoints were objective response rates, disease control rates, and safety, and overall survival. This study was registered at ClinicalTrials.gov, NCT04338438. Between April 2015 and May 2019, we included 37 patients with advanced gastric or gastro-oesophageal junction adenocarcinoma refractory to first-line platinum-containing therapy. At the data cutoff, the 6-month progression-free survival was 31.5%, the median progression-free survival and overall survival were 4.2 (95% CI: 3.50-4.90) months and 8.2 (95% CI: 4.69-11.71) months, respectively. Of 37 eligible patients, 8 (21.6%) patients reached objective responses, 31 (83.8%) patients reached disease control. Grade 3 or 4 adverse events occurred in 8 (21.6%) patients, including hand-foot syndrome, hypertension, and diarrhea, etc. The combination of Apatinib and S-1 showed promising efficacy and manageable toxicity as a home-based, second-line therapy in patients with advanced gastric or gastro-oesophageal junction adenocarcinoma, especially for the elder patients with poor performance status. NCT04338438.