DIET & NUTRITION 
PATIENT EDUCATION 
OBESITY/WEIGHT MANAGEMENT 
EXERCISE/TRAINING 
LEGAL MATTERS 
GUIDELINES/RECOMMENDATIONS The RASolute 302 trial randomized adults with metastatic PDAC who had received one prior fluoropyrimidine- or gemcitabine-based regimen to oral daraxonrasib (300 mg daily) or investigator’s choice of standard chemotherapy. More than 90% of PDAC tumors harbor an oncogenic RAS mutation, yet no RAS-targeted therapy has been approved for this disease.
Clinical Considerations
- Daraxonrasib reduced the risk of death by 60% vs. chemotherapy in RAS G12 patients (HR 0.40; median OS 13.2 vs. 6.6 months)
- Survival benefit was consistent across RAS G12, G13, Q61 mutations, and wild-type RAS — broadening the potentially eligible population
- Objective response rate was 31.6% vs. 11.2% in the overall population; dose reductions were less frequent with daraxonrasib than chemotherapy (36.1% vs. 57.5%)
- Patient-reported outcomes showed daraxonrasib significantly delayed deterioration in pain and global health/quality-of-life scores
Practice Applications
- Monitor for trial publication in NEJM and anticipated FDA submission from Revolution Medicines as the regulatory pathway develops
- Recognize rash and stomatitis as the primary dose-limiting toxicities requiring management planning
- Anticipate second-line PDAC protocols to be reconsidered as society guidance responds to this data
- Consider RAS pathway status in biomarker documentation for patients with metastatic PDAC, though benefit extended beyond RAS G12
