The BREAKWATER Trial Explores Braftovi, Erbitux and Chemo in BRAF V600E+ mCRC

Among patients with BRAF V600E-mutant metastatic colorectal cancer (mCRC), early findings from the phase 3 BREAKWATER clinical trial suggest a sustained survival advantage with Braftovi (encorafenib) and Erbitux (cetuximab) with or without chemotherapy (FOLFOX) versus chemotherapy alone.

BREAKWATER showed that adding Braftovi and Erbitux to FOLFOX chemotherapy significantly improved patient response rates, with 60.9% of patients responding to the combination therapy compared with 40% responding to the standard chemotherapy. The responses were both rapid and long-lasting.

Moreover, the treatment regimen was generally well-tolerated, with no unexpected safety concerns. These findings highlight the potential utility of Braftovi and Erbitux plus FOLFOX, and were shared in a presentation at the at the 2025 ASCO Gastrointestinal Cancers Symposium.

In an interview with CURE, Dr. Scott Kopetz, the presenting study author, shared what conversations a patient should have with their oncologist, should they have BRAF V600E-mutant mCRC, in light of these findings. Kopetz currently serves as Deputy Chair for Translational Research and a Professor in the Department of Gastrointestinal (GI) Medical Oncology, Division of Cancer Medicine; leader of the Department of Cancer Center Support Grant, GI Program; TRACTION Medical Director, Division of Therapeutics Discovery Division; and Associate Vice President for Translational Integration, all at The University of Texas MD Anderson Cancer Center, in Houston.

Transcript:

This is a finding that really reiterates the importance of knowing the molecular subtype of your cancer before — or shortly after — initiating first line therapy. The idea is that the best therapies, the best outcomes, come when we can really personalize and tailor the therapies, even with the first initial chemotherapy.

Sometimes this takes time. It takes time to get this molecular testing data back, to integrate it, to get started on the treatments. So we're always encourage patients to talk to their providers, and for providers to make sure that this testing is done in a timely manner, recognizing that sometimes a dose or two of chemotherapy with FOLFOX [chemotherapy] alone, for example, may be needed before we have all this information in the real world. This is certainly very reasonable, then, to do that and to switch a patient on to a Braftovi, Erbitux and FOLFOX [chemotherapy] regimen after a cycle or two in the presence of a BRAF mutation.

Transcript has been edited for clarity and conciseness.

Reference:

“BREAKWATER: Analysis of first-line encorafenib + cetuximab + chemotherapy in BRAF V600E-mutant metastatic colorectal cancer..” Kopetz S, et al. J Clin Oncol.

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