Case Report: Durable complete response to olaparib in a patient with BRCA2-driven metastatic gastric adenocarcinoma after failure of chemo-immunotherapy

Metastatic gastric adenocarcinoma is associated with poor prognosis and limited treatment options after failure of chemotherapy and immunotherapy. Although BRCA1/2 alterations are well-established predictive biomarkers for PARP inhibitor efficacy in several malignancies, their role in gastric cancer remains incompletely defined. We report a 65-year-old male with metastatic gastric adenocarcinoma who underwent gastrectomy with intraoperatively detected liver metastases. The disease progressed following platinum-based chemotherapy combined with nivolumab and subsequent paclitaxel-ramucirumab therapy. Comprehensive genomic profiling using the Tempus xT assay identified a pathogenic germline BRCA2 frameshift mutation with somatic loss of heterozygosity. Based on this molecular profile, off-label olaparib therapy was initiated. The patient achieved a complete metabolic response on FDG PET-CT, which has been sustained for more than three years under continuous olaparib therapy with acceptable tolerability. This case highlights the importance of molecularly guided treatment strategies and homologous recombination repair deficiency in selected patients with advanced gastric cancer.