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

Abstract

Background: 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.

Methods: 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.

Results: 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.

Conclusions: 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.

Trial registration: NCT04338438.

Keywords: Molecular targeted therapy; S-1; apatinib; stomach neoplasms.

Conflict of interest statement

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://dx.doi.org/10.21037/jgo-21-186). All authors report that the study was supported by National Key Technologies R&D Program (No. 2015BAI13B09) and China Anti-Cancer Association-Hengrui Pharmaceutical Innovative Drugs Clinical Research Fund. The authors have no other conflicts of interest to declare.

2021 Journal of Gastrointestinal Oncology. All rights reserved.

Figures

Figure 1

Trial profile.

Figure 2

Kaplan-Meier curve for (A) OS and (B) PFS in patients with at least one post-baseline efficacy assessment (n=37).

Figure 3

Waterfall plot for the best percentage change in target lesions size. This plot shows the best percentage change in sum of the longest target lesion diameters of 37 patients who had at least one post-baseline efficacy assessment.

Figure 4

Kaplan-Meier curve for subgroup analysis. (A) The overall survival of patients with (n=14) and without radical gastrectomy (n=23). (B) The progression-free survival the overall survival of patients with and without radical gastrectomy. (C) The overall survival of patients with (n=21) and without ascites (n=16). (D) The progression-free survival of patients with and without ascites.