Clinical benefit of continuation of PD-1 inhibitors after progression on first-line chemoimmunotherapy in metastatic gastric cancer and biomarker exploration.

Abstract

Background: Whether continuing immunotherapy after progression in second-line settings of metastatic gastric cancer (MGC) remains unclear. Herein, we explored the efficacy of PD-1 inhibitors for MGC after progression on previous chemoimmunotherapy.

Methods: We retrospectively identified MGC patients who received oxaliplatin-based chemotherapy plus PD-1 inhibitor, with or without trastuzumab, as first-line treatment. The patients received treatment with or without PD-1 inhibitors beyond progression in patients with MGC were divided into treatment beyond progression (TBP) group and non-TBP (NTBP) group. The median progression free survival (PFS) and overall survival (OS) from the start of treatment after progression were assessed.

Results: The mOS and mPFS in the TBP group was significantly longer than that in the NTBP group (mOS: 9.0 vs. 5.0 months, P = 0.011; mPFS: 4.3 vs. 2.7 months, P = 0.03). Moreover, TBP was an independent prognostic factor for both PFS and OS in multivariate analysis. In the subgroup analysis, patients who were male, had a favorable ECOG (0-1), classified into diffuse histologic subtype and achieved disease control in the prior chemoimmunotherapy, might be more likely to benefit from continuing immunotherapy compared to discontinuation beyond progression.

Conclusion: PD-1 inhibitors based therapeutic strategy may be a reasonable option in second-line setting for MGC who progressed on prior immunotherapy. Further larger prospective trials are warranted to validate these findings.