Case 1 Deep Dive: Treatment Individualization, Dose Modification, and Preserving the Path to Second Line

This segment centers on a 67-year-old male with ECOG PS 1 metastatic PDAC, a KRAS G12D mutation, elevated CA 19-9, and limited social support. The discussion walks through how patient-specific factors including functional independence concerns and lack of caregiver support shape the triplet versus doublet decision. The Phase 3 RASolute 302 top-line results, demonstrating a significant overall survival benefit for daraxonrasib in the second-line setting, median OS 13.2 versus 6.7 months, HR 0.40, reinforce the importance of preserving performance status to reach subsequent therapies. Dose modification strategies are addressed directly, citing post-hoc analyses from NAPOLI 3 confirming that dose delays and reductions do not compromise clinical outcomes. The segment also covers UGT1A1 polymorphism testing, biweekly scheduling strategies, and the core philosophy that treatment duration rather than intensity is the true driver of long-term benefit in mPDAC.