Breakthrough Treatment for Metastatic Colorectal Cancer Shows Promising Results
A recent study presented at the 2025 ASCO Annual Meeting has revealed that a targeted therapy combination of encorafenib and cetuximab with mFOLFOX6 chemotherapy may significantly improve survival rates for patients with BRAF V600E–mutant metastatic colorectal cancer. According to research published on Asco Post, the international phase III BREAKWATER trial demonstrated a substantial benefit in overall survival, progression-free survival, and objective response rates with the encorafenib/cetuximab combination with mFOLFOX6 chemotherapy.
The study, led by Dr. Elena Elez of Vall d’Hebron Institute of Oncology, Barcelona, found that patients treated with encorafenib/cetuximab and mFOLFOX6 had a median overall survival of 30.3 months, compared to 19.5 months with encorafenib/cetuximab alone and 15.1 months in the control arm. As quoted in the Asco Post article, Dr. Elez stated, "BRAF V600E–mutant metastatic colorectal cancer is characterized by its aggressive nature, and the standard therapeutic options have limited efficacy." The study included 637 participants, with a median age of approximately 60 years, and about half were women.
The BREAKWATER trial was designed to test the BRAF inhibitor encorafenib and the EGFR inhibitor cetuximab, with or without mFOLFOX6, for BRAF V600E-mutant metastatic colorectal cancer. The encorafenib/cetuximab combination with and without mFOLFOX6 was compared with the current standard-of-care treatment of chemotherapy with or without bevacizumab. The study originally included three treatment arms: encorafenib/cetuximab alone, encorafenib/cetuximab with mFOLFOX6, and the control arm of chemotherapy with or without bevacizumab.
The results showed that patients treated with encorafenib/cetuximab with mFOLFOX6 had a 51% lower risk of dying than patients treated with the standard-of-care chemotherapy with or without bevacizumab. Progression-free survival was 12.8 months in the encorafenib/cetuximab plus mFOLFOX6 arm, 6.8 months in the encorafenib/cetuximab alone arm, and 7.1 months in the control arm. The objective response rates were 65.7% in the encorafenib/cetuximab plus mFOLFOX6 arm, 45.6% in the encorafenib/cetuximab alone arm, and 37.4% in the control arm.
According to Asco Post, most of the side effects for these treatments were reported to be manageable. Serious side effects caused by the treatments occurred in 30% of patients in the encorafenib/cetuximab alone arm, 46% of the encorafenib/cetuximab with mFOLFOX6 arm, and 39% of the control arm. The most common side effects for the encorafenib/cetuximab with mFOLFOX6 treatment were nausea, anemia, and diarrhea.
The findings of this study have significant implications for the treatment of BRAF V600E–mutant metastatic colorectal cancer. As noted by Dr. Joel Saltzman, Vice Chair of Regional Oncology at Taussig Cancer Center, Cleveland Clinic, and an ASCO expert in gastrointestinal cancers, "This trial continues to move the needle forward to a more personalized approach to care based on the molecular and genetic characteristics of metastatic colon cancer. This trial establishes front-line encorafenib, cetuximab, and FOLFOX as the new standard of care for BRAF V600E–mutant metastatic colorectal cancer."
The study was funded by Pfizer, and full disclosures of the study authors can be found on coi.asco.org. Researchers will continue to study the encorafenib/cetuximab combination with the FOLFIRI regimen. The results of this study, as reported by Asco Post, provide new hope for patients with BRAF V600E–mutant metastatic colorectal cancer, and may pave the way for more effective treatment options in the future.
The BREAKWATER trial results mark a significant milestone in the treatment of metastatic colorectal cancer, and Asco Post reports that this study will likely change the way clinicians approach treatment for patients with BRAF V600E–mutant metastatic colorectal cancer. Further studies will be necessary to confirm these findings and to explore the potential of this treatment combination in other patient populations.
In conclusion, the study published on Asco Post highlights the importance of targeted therapy in the treatment of metastatic colorectal cancer. By understanding the molecular and genetic characteristics of this disease, clinicians may be able to provide more effective treatment options for patients. The results of the BREAKWATER trial are a promising step forward in this effort, and Asco Post will continue to provide updates on this and other studies in the field of oncology.
