ASCO 2026
Progression-free survival nearly doubles with Braftovi triplet in metastatic colorectal cancer
Clinical takeaway: For previously untreated BRAF V600E-mutant metastatic colorectal cancer, Braftovi (encorafenib) plus cetuximab and fluorouracil-based chemotherapy is now strongly supported as a first-line option, offering substantially improved disease control and survival versus chemotherapy in this high-risk subgroup.
BRAF V600E-mutant metastatic colorectal cancer is associated with particularly poor prognosis and has historically lacked effective targeted options. New data from cohort 3 of the phase 3 BREAKWATER trial, presented at the 2026 ASCO meeting, provide additional evidence supporting Braftovi (encorafenib) in combination with Erbitux (cetuximab) and FOLFIRI for this biomarker-defined population.
The randomized cohort compared Braftovi plus cetuximab and FOLFIRI against FOLFIRI with or without bevacizumab in previously untreated patients. Median progression-free survival nearly doubled with the targeted regimen, reaching 15.2 months versus 8.3 months with the comparator. This corresponded to a 56% reduction in the risk of disease progression or death (hazard ratio [HR], 0.44; 95% confidence interval [CI], 0.27–0.70; P=0.0002).
Overall survival outcomes also favored the triplet regimen. The risk of death was reduced by 44% (HR, 0.56; 95% CI, 0.34–0.94), with median overall survival not yet reached in the encorafenib arm versus 20.3 months in the control group. At 18 months, survival rates were 72% with the targeted regimen compared with 54.5% for standard therapy.
Safety findings were consistent with the known profiles of the individual agents, with no new safety signals observed. Grade 3 or higher adverse events occurred in 70.4% of patients receiving the Braftovi regimen versus 80.9% of those receiving chemotherapy, although discontinuation rates were slightly higher with the triplet.
The magnitude of benefit—particularly the near doubling of progression-free survival—provides definitive phase 3 evidence supporting earlier use of BRAF-targeted therapy and reinforces a shift toward upfront biomarker-directed treatment in this high-risk population.
“For people with BRAF V600E-mutant metastatic colorectal cancer – a disease that historically has had no targeted treatment options and poor outcomes – these results strengthen confidence in how we can treat this disease,” said Scott Kopetz, MD, PhD, FACP, of The University of Texas MD Anderson Cancer Center and co-principal investigator of the BREAKWATER trial. “A nearly 60% reduction in risk of disease progression or death, combined with prolonged overall survival, reinforces the role of encorafenib in combination with cetuximab and FOLFIRI as a standard of care in the first-line setting for this patient population.”
Source: Pfizer Inc. (2026, May 31). Press release. Pfizer’s BRAFTOVI regimen nearly doubles median progression-free survival in metastatic colorectal cancer