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 resulted in patients having better responses and slower disease progression.
  • The BREAKWATER study can potentially change the approach to care for colon cancer patients by prompting early biomarker testing.

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.

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 in frontline treatment.

Dr. Susan Zhang, a global development lead at Pfizer, expressed excitement about the findings presented at this year’s American Society of Clinical Oncology (ASCO) annual meeting.

“The BREAKWATER study has met its dual primary endpoint of response and progression-free survival, as well as the key secondary endpoint of overall survival,” Dr. Zhang tells SurvivorNet Connect.

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

According to Dr. Zhang, 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

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.

Dr. Zhang emphasized the importance of biomarker testing for these patients as 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. Dr. Zhang hopes the BREAKWATER trial changes that approach.

“I hope that with a positive BREAKWATER trial, people can start to understand the importance of checking biomarkers,” Dr. Zhang said.

FDA Approval and Future Directions

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 — yet more work needs to be done to raise awareness and make sure patients are getting the proper testing.

Dr. Zhang believes biomarker testing should be prioritized early in the diagnostic process, potentially before the cancer returns or recurs. Liquid biopsy is emerging as a valuable tool for less invasive testing.

“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,” Dr. Zhang noted.