Case 2: Germline BRCA2, KRAS G12V, and Sequencing Strategies in a Young, Fit Patient

A 54-year-old female with pancreatic tail PDAC, bilateral nodules, a germline BRCA2 pathogenic variant, and a KRAS G12V somatic mutation presents a compelling case for molecularly informed treatment planning. The discussion explores how HRR pathway mutations increase sensitivity to platinum-based chemotherapy, making a triplet regimen the preferred frontline approach. The germline BRCA2 status also positions this patient as a strong candidate for olaparib maintenance therapy based on the POLO trial data. The conversation then pivots to the transformative RASolute 302 results, where daraxonrasib, targeting RAS in its active GTP-bound ON state, achieved a median overall survival of 13.2 months in the second-line setting, representing a hazard ratio of 0.40 and a 60% improvement over standard chemotherapy. With KRAS mutations present in approximately 90% of PDAC cases, this data signals a paradigm shift in how oncologists counsel patients about their full treatment journey from diagnosis.mPDAC.