BRAF V600E mutations are identified in 8%–12% of patients with mCRC and confer a poor prognosis. Pfizer’s Encorafenib, a BRAF inhibitor has been approved in combination with cetuximab, anti-EGFR antibody, for the treatment of previously treated patients with BRAF V600E-mutant mCRC based on the Phase III BEACON study. 

A Phase III-BREAKWATER study is being conducted to evaluate encorafenib with or without + chemotherapy (FOLFIRI) in patients with previously untreated BRAF V600E-mutant mCRC. The updated results, approximately 28 months after the last patient was enrolled, from the Encorafenib + FOLFIRI cohort of the safety lead-in (SLI), along with the final pharmacokinetic data were presented in the Mini Oral Session at the ESMO 2024. A total of 30 participants were enrolled in the EC + FOLFIRI cohort of the SLI as the data cutoff. 

The table below shows the antitumor activity by line of therapy.

In terms of safety, the Encorafenib + FOLFIRI regimen was generally well-tolerated, with no new safety concerns observed. One patient experienced a dose-limiting toxicity of Grade 4 neutropenia lasting over 7 days, while no other DLTs were reported. Serious adverse events of any cause occurred in 46.7% of patients.

Conclusion 

Historically, the first-line treatment of BRAF V600E-mutant mCRC with chemotherapy regimens had limited efficacy. Currently, there are no specifically targeted first-line treatments for BRAF V600E-mutant mCRC, which highlights the unmet need for novel treatment options for this patient population. The updated results from the Phase III-BREAKWATER study demonstrated that Encorafenib + FOLFIRI regime was tolerable without new safety signals in patients with BRAF V600E-mutant mCRC who had been treated with 1 or fewer prior lines of systemic therapy for metastatic disease. The combination also showed promising results in the improvement of key efficacy measures (ORR, PFS, and OS), supporting the continued evaluation of this combination.  

For more insight into the patient's burden/epidemiology, treatment, and changing market landscape-related advancements, refer to the following reports: 

• Colorectal Cancer - Market Insight, Epidemiology and Market Forecast - 2032

• Metastatic Colorectal Cancer Market Insight, Epidemiology and Market Forecast – 2032