Triple therapy regimen significantly improves survival in BRAF V600E-mutated metastatic colorectal cancer

Medical Xpress / University of Texas M. D. Anderson Cancer Center / New England Journal of Medicine ^ | May 30, 2025 | Elena Elez et al

[ConservativeMind]

First-line treatment with the triplet combination of encorafenib, cetuximab and mFOLFOX6 significantly improved survival compared to the standard of care in patients with BRAF V600E-mutated metastatic colorectal cancer, according to data from the Phase III BREAKWATER trial.

The findings demonstrated significantly longer progression-free survival (PFS) and overall survival (OS) compared to standard chemotherapy-based regimens. The median PFS was 12.8 months with the triplet combination compared to 7.1 months in the standard-of-care group, and the median OS was 30.3 months compared with 15.1 months, respectively.

"The latest data from the BREAKWATER trial further confirms that targeting the BRAF V600E mutation up front, with encorafenib, cetuximab and mFOLFOX6, offers a clear survival advantage over standard chemotherapy," said Scott Kopetz, M.D., Ph.D.

"The combination reduced the risk of disease progression or death by 47% and cut the risk of death in half compared to standard care. This represents an unprecedented improvement for patients with this mutation."

Colorectal cancer affects more than 150,000 individuals annually in the U.S., according to the National Cancer Institute. BRAF mutations, present in approximately 8 to 12% of colorectal cancer cases, are associated with a distinct molecular subtype characterized by aggressive tumor biology and poor clinical outcomes, with median OS typically under 12 months.

Encorafenib and cetuximab are targeted therapies designed to counteract the activity of proteins that drive cancer progression when BRAF V600E mutations are present. Chemotherapy regimen mFOLFOX6 is commonly used in treating colorectal cancer. Standard treatments typically involve chemotherapy without targeted BRAF inhibition.

The safety data from this trial continues to show that the triplet therapy regimen caused Grade 3 or higher adverse events in more than half the patients, although the adverse events were largely reversible.

The trial reinforces the importance of routine molecular profiling to guide early targeted therapy selection for colorectal cancer patients.

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TOPICS: Health/Medicine
KEYWORDS: cancer; chemotherapy; colon; colorectal; metastatic; mutated; treatment

[ConservativeMind]

This basically cut the risk of death in half and is available today.

[ConservativeMind]

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