Updated June 9th, 2025

New Drug Combination For Advanced Colon Cancer Highlights The Importance Of Biomarker Testing: What Patients Need To Know

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A More Effective Option For Some Colon Cancer Patients

New data indicates that a combination therapy — encorafenib (a BRAF inhibitor), cetuximab (an EGFR inhibitor), and chemotherapy combination mFOLFOX6 — leads to better survival when given as a first treatment for patients with a specific type of advanced colon cancer with a BRAF V600E mutation.
About 10 to 15% of colorectal cancers have a BRAF mutation, and most of those are the BRAF V600E mutation.
In the BREAKWATER trial, where the combination approach was compared to the current standard for these patients, the new treatment approach resulted in patients having better responses and slower disease progression.

The BREAKWATER study can potentially change the standard of care for colon cancer patients by prompting early biomarker testing, which tests a patient’s blood for the BRAF gene mutation. This testing can clear a pathway to accessing more effective treatment sooner.

A groundbreaking study is providing new hope for patients with advanced or metastatic colon cancer, particularly those with something known as a BRAF V600E mutation, a historically difficult-to-treat subtype.

BRAF gene mutations have the potential to cause normal cells to become cancerous. About 10 to 15% of colorectal cancers have a BRAF mutation, and most of those are the BRAF V600E mutation.

The BREAKWATER study, a global phase III clinical trial, has shown promising results in improving survival outcomes and advancing biomarker testing — or testing to understand genetic characteristics of a patient’s cancer — in frontline treatment (the initial treatment for a newly diagnosed cancer patient).

The trial compared a combination therapy — encorafenib (brand name: Braftovi), a BRAF inhibitor, and cetuximab, which inhibits a type of mutation known as the epidermal growth factor receptor (EGFR), plus the standard chemotherapy approach, modified FOLFOX6 (mFOLFOX6) to the current standard of care approach.

According to Dr. Susan Zhang, author of the study, the combination therapy significantly improved outcomes, with a 47% reduction in the risk of disease progression and death and a 51% reduction in mortality, effectively doubling survival rates. She explains that she hopes the results of this recent study will lead to biomarker testing being prioritized for more patients.

Addressing An Urgent Need

Colorectal cancer (also called colon cancer) is the third most common cancer worldwide and the second leading cause of cancer-related deaths globally. Colorectal cancer is a type of cancer that affects your large intestine (colon) or the end of your intestine (rectum). The cancer starts when abnormal lumps called polyps grow in the colon or rectum. If you don’t have these polyps removed, they can sometimes change into cancer.

For patients with BRAF V600E mutations, survival rates have been historically half that of patients without the mutation. BREAKWATER is a major breakthrough, as no significant frontline advancements have been made in this space for over 15 years.

The study draws attention to the importance of biomarker testing, which involves identifying specific aspects of cancer behavior. By identifying particular genetic, molecular, or protein markers linked to cancer growth, biomarker testing allows oncologists to tailor treatments to the specific characteristics of each patient’s tumor.

Colon cancer patients tend to undergo biomarker testing less frequently compared to those with breast or lung cancer due to a lack of effective targeted therapies.

FDA Approval and Future Directions

The findings of BREAKWATER have already influenced patient care. In December of last year, the FDA approved encorafenib plus cetuximab and mFOLFOX for metastatic colorectal cancer patients with BRAF mutations. This marks a crucial step toward improving treatment strategies.

WATCH: Understanding liquid biopsies for cancer.

Biomarker testing should be prioritized early in the diagnostic process, potentially before the cancer returns or recurs. Liquid biopsy, a simple blood draw that detects tumor DNA, is emerging as a valuable tool for less invasive testing.

Of note, colorectal cancer patients, especially those with BRAF mutations, shed a lot of tumor DNA into the blood. So, the detectability rate of a liquid biopsy is pretty high.