Elena Elez, MD, PhD, on Updated Survival Data From the BREAKWATER Trial

We know that between 8 to 12% of patients with metastatic colorectal cancer have BRAF V600E–mutated metastatic colorectal cancer. What we know from these illnesses is that it's a poor prognosis group of patients, so the first-line treatments that we have have really limited efficacy, and this was the basis for developing a phase three clinical trial in this patient population. We know as well that encorafenib is an ATP-competitive BRAF inhibitor that, combined with cetuximab, was approved for treatment in the second and third line of metastatic colorectal cancer in this patient population. What we are doing now is exploring the combination of encorafenib, cetuximab, and FOLFOX in frontline therapy for this patient population, compared to encorafenib and cetuximab alone or the standard of care, which is chemotherapy combined with bevacizumab or not. The dual primary endpoint of this clinical trial was progression-free survival and overall response rate, and the secondary objective of this clinical trial was overall survival. Indeed, the results of the BREAKWATER trial were presented at the beginning of 2025. We had the results of overall response rate—the study met one of its primary endpoints—and what we are presenting now at ASCO 2025 are the results of progression-free survival, the other dual primary endpoint, and results on overall survival. Regarding the patient population, it was well balanced. It's nice to see that we have a representation of patients with high tumor burden, meaning three or more metastatic sites of metastasis as well as liver metastasis. Regarding the results on overall survival, the combination of FOLFOX, encorafenib, and cetuximab was statistically significant and clinically meaningful, superior compared to the standard of care. In this case, we found 30 months of overall survival for the patients treated with encorafenib, cetuximab, and FOLFOX, and 15 months for those patients treated with the standard of care. This represents a paradigm change in the treatment of metastatic colorectal cancer harboring a BRAF V600E mutation, and this regimen will be a new standard of care in the frontline setting for this patient population.