Prognostic implications of tissue-based homologous recombination deficiency in metastatic gastric cancer treated with immune checkpoint inhibitor plus chemotherapy - PubMed
4 hours ago
- #Homologous Recombination Deficiency
- #Immunotherapy
- #Gastric Cancer
- This study included 139 metastatic gastric cancer (mGC) patients treated with first-line nivolumab plus chemotherapy, of whom 116 underwent tissue-based next-generation sequencing (NGS).
- HRD-positive tumors (14.7% of sequenced patients) were significantly associated with longer progression-free survival (PFS; median 23.1 vs. 9.6 months, p=0.032) and overall survival (OS; median not reached vs. 17.9 months, p=0.027) compared to HRD-negative tumors.
- HRD positivity remained an independent favorable prognostic factor for OS in multivariate analysis (HR: 0.247; 95% CI 0.071-0.859; p=0.028).
- HRD-positive tumors showed higher frequencies of high tumor mutational burden (TMB) and microsatellite instability-high (MSI-high) status.
- An exploratory analysis of ctDNA-based HRD in a small subset (n=24) did not demonstrate a statistically significant association with survival outcomes.
- The study suggests tissue-based HRD positivity may provide complementary prognostic information in mGC patients treated with first-line immune checkpoint inhibitor plus chemotherapy.