The Headline: Daraxonrasib delivered what may be the most impressive survival improvement ever reported for treatment-refractory metastatic pancreatic cancer.
The Study: Gains with second-line treatment for pancreatic cancer is typically measured in weeks, not months. In the phase 3 RASolute 302 trial, 500 patients progressing after first-line therapy for metastatic pancreatic adenocarcinoma (no specific mutations required) were randomized to the oral RAS-inhibitor daraxonrasib versus investigator’s choice second-line chemo. Incredibly, daraxonrasib doubled median progression-free survival (7.32 vs 3.6 months; HR 0.49) mirrored by a doubling of overall survival (13.2 vs 6.7 months; HR 0.40). Adverse effects also favored daraxonrasib despite longer administration: grade 3+ events occurred in 44% versus 58% with chemotherapy, discontinuations were rare (1.2% vs 11.2%), and dose intensity remained high.
TBL: Look for oral RAS-inhibitors to be investigated in first-line treatment algorithms for all-types of pancreatic cancer. | Wolpin, ASCO 2026
The Study: Gains with second-line treatment for pancreatic cancer is typically measured in weeks, not months. In the phase 3 RASolute 302 trial, 500 patients progressing after first-line therapy for metastatic pancreatic adenocarcinoma (no specific mutations required) were randomized to the oral RAS-inhibitor daraxonrasib versus investigator’s choice second-line chemo. Incredibly, daraxonrasib doubled median progression-free survival (7.32 vs 3.6 months; HR 0.49) mirrored by a doubling of overall survival (13.2 vs 6.7 months; HR 0.40). Adverse effects also favored daraxonrasib despite longer administration: grade 3+ events occurred in 44% versus 58% with chemotherapy, discontinuations were rare (1.2% vs 11.2%), and dose intensity remained high.
TBL: Look for oral RAS-inhibitors to be investigated in first-line treatment algorithms for all-types of pancreatic cancer. | Wolpin, ASCO 2026