EPISODE-III and RASolute 302 Data From ASCO 2026
Key Points
- Adjuvant aspirin did not show a disease-free survival (DFS) benefit in unselected patients with stage III colorectal cancer in the EPISODE-III trial, although further analyses are ongoing.
- The RASolute 302 trial showed daraxonrasib offered an unprecedented survival benefit for patients with metastatic pancreatic cancer.
Cathy Eng, MD, FACP, FASCO, of Vanderbilt-Ingram Cancer Center, and Carolina Bernabe Ramirez, MD, of Montefiore Einstein Comprehensive Cancer Center, discussed the EPISODE-III trial and the transformative data from the RASolute 302 trial presented at the 2026 American Society of Clinical Oncology Annual Meeting (ASCO 2026).
The EPISODE-III trial sought to clarify the potential benefit of adjuvant aspirin in unselected patients with stage III colorectal cancer. The study randomized patients with postresection stage III colorectal cancer to low-dose aspirin or matched placebo for 3 years alongside standard adjuvant chemotherapy. After 4 years of median follow-up, low-dose aspirin showed a numerical but not significant improvement in DFS for unselected stage III colorectal cancer.
Further biomarker analyses and a meta-analysis of randomized trials are planned as part of EPISODE-III. If these produce stronger positive data, oncologists may no longer need to screen for PI3K/PIK3CA alterations to select patients for adjuvant low-dose aspirin, which would be a major update to the existing paradigm based on the ALASCCA trial, said Dr. Eng.
The doctors also joined in the excitement regarding the data that was to be presented from the RASolute 302 trial. The groundbreaking data uproot the historical perspective that RAS mutations in pancreatic cancer are not targetable. Moreover, the mechanism of daraxonrasib makes it effective against a broad range of RAS alterations, distinct from currently available KRAS mutation–selective inhibitors.