Pfizer announced statistically significant and clinically meaningful survival results from the Phase 3 breakwater trial evaluating Braftovi (encorafenib) in combination with cetuximab (marketed as Erbitux) and mFolfox6 (fluorouracil, leucovorin, and oxaliplatin) in patients with metastatic colorectal cancer (mCRC) with a BRAF V600E mutation.

These data will be presented today in an oral presentation (Abstract LBA3500) at the 2025 American Society of Clinical Oncology (ASCO) Annual Meeting and have been simultaneously published in the New England Journal of Medicine.

“Patients with metastatic colorectal cancer whose tumors harbor a BRAF V600E mutation generally face a daunting prognosis, as this aggressive tumor often does not respond well to standard-of-care chemotherapy,” said Elena Élez, M.D., Ph.D., senior investigator at Vall d’Hebron Institute of Oncology in Barcelona, Spain, and co-principal investigator of the BREAKWATER trial.

“The BREAKWATER results are the first promising survival outcomes ever reported for BRAF-mutant metastatic colorectal cancer in the first-line setting, representing a practice-changing breakthrough for patients.”

CRC is the third most common type of cancer in the world1BRAF mutations are estimated to occur in 8-12% of people with mCRC and represent a poor prognosis. The BRAF V600E mutation is the most common BRAF mutation and the risk of mortality in patients with CRC harboring this mutation is more than double that of patients with no known BRAF mutation present.

“The BRAFTOVI combination helped significantly reduce the risk of disease progression or death, potentially altering the course of disease for people with metastatic colorectal cancer with a BRAF V600E mutation,” said Johanna Bendell, M.D., Chief Oncology Development Officer, Pfizer. “These unprecedented results from the BREAKWATER trial further establish the benefit of the BRAFTOVI combination regimen and its potential to become a new standard-of-care, building on Pfizer’s legacy in precision medicine and commitment to delivering breakthrough medicines that help people with cancer live better and longer lives.”

The BRAFTOVI combination regimen received accelerated approval by the U.S. Food and Drug Administration (FDA) in December 2024 for patients with BRAF V600E -mutant mCRC based on a clinically meaningful and statistically significant improvement in confirmed ORR in treatment-naïve patients, the study’s other dual primary endpoint.