The RASolute 302 Phase III randomized controlled trial (n=500, multicenter across North America, Europe, Asia) demonstrated daraxonrasib doubling median overall survival to 13.2 months versus 6.7 months with chemotherapy in second-line metastatic pancreatic cancer (HR 0.40), alongside PFS gains (7.2 vs 3.6 months) and improved objective response rates (31.6% vs 11.2%). Published simultaneously in NEJM following ASCO 2026 plenary presentation, this RCT design provides higher-grade evidence than prior observational KRAS cohorts. More than 90% of pancreatic tumors harbor KRAS mutations; daraxonrasib's multi-selective RAS(ON) inhibition addresses this directly, unlike earlier single-mutant agents such as sotorasib whose modest activity was documented in smaller Phase I/II studies (e.g., CodeBreaK 100). Original coverage understates potential resistance mechanisms and financial toxicity; real-world data from similar targeted agents show 20-30% dropout from adverse events within six months. Spillover implications extend to colorectal and non-small cell lung cancers where RAS alterations drive 30-40% of cases, though cross-trial heterogeneity in mutation subtypes requires dedicated basket studies. Revolution Medicines sponsorship introduces clear conflicts of interest that warrant independent confirmatory trials before broad adoption.