Pembrolizumab plus chemotherapy following lack of response to nivolumab-based therapy in MSI-High/dMMR advanced gastric cancer: a case report.

Abstract

Microsatellite instability-high (MSI-H) or deficient mismatch repair (dMMR) gastric cancer is generally sensitive to immune checkpoint inhibitors (ICIs); however, the clinical role of re-administration of ICI plus chemotherapy after an initial lack of response remains unclear. We report a 76-year-old man with HER2-negative advanced gastric adenocarcinoma who exhibited no clear radiologic response and worsening gastric outlet obstruction after two cycles of first-line SOX (S-1 plus oxaliplatin) with nivolumab, necessitating gastrojejunostomy. He subsequently received ramucirumab-based therapy, paclitaxel, and irinotecan. Genomic profiling revealed MSI-H/dMMR with loss of MLH1 and PMS2 expression. Pembrolizumab combined with capecitabine and oxaliplatin (CAPOX) was initiated as fifth-line therapy, resulting in notable regression of hepatic and nodal metastases. This case underscores the clinical importance of early MSI/MMR and genomic testing and suggests that re-administration of ICI plus chemotherapy may be a therapeutic option for selected patients with advanced gastric cancer who initially show limited response to ICI-based therapy.