Effects of genome-wide modifiers of response to next-generation FGFR inhibitors in solid tumors—An Indian multicentric study.

e23422 Background: FGFR alterations are established actionable drivers in solid tumors, with particular clinical relevance in hepatobiliary malignancies. The advent of selective and next-generation FGFR inhibitors has expanded therapeutic options; however, durable responses remain inconsistent. Emerging evidence suggests that co-occurring genomic alterations significantly influence sensitivity and resistance to FGFR-directed therapies. We report a large Indian multicentric genomic analysis evaluating FGFR alterations, actionability, and resistance mechanisms with direct relevance to contemporary FGFR inhibitors. Methods: Comprehensive genome-wide next-generation sequencing data from 791 patients with solid tumors across multiple Indian centers were analyzed. Alterations in FGFR1–4 were characterized by type, oncogenicity, and clinical actionability. Known and putative resistance mechanisms—including FGFR gatekeeper mutations and co-alterations in bypass signaling pathways—were systematically evaluated. Results: A total…