Dr. Mizrahi on Optimal Sequencing in BRAF V600E-Mutant mCRC

Jonathan Mizrahi, MD, fellow at The University of Texas MD Anderson Cancer Center, discusses optimal sequencing in patients with BRAF V600E-mutant metastatic colorectal cancer (mCRC).

Patients with BRAF V600E-mutant mCRC can receive a chemotherapy doublet, such as FOLFOX or FOLFIRI, in the frontline setting, says Mizrahi. Upon progression, the alternate regimen can be used. However, data from the phase III TRIBE2 trial showed that the combination of FOLFOXIRI and bevacizumab (Avastin) led to an improvement in progression-free survival 2 versus sequential use of FOLFOX/bevacizumab and FOLFIRI/bevacizumab in patients with mCRC. In the context of patients with BRAF-mutant mCRC, who have worse prognosis, Mizrahi recommends using FOLFOXIRI/bevacizumab in the frontline setting.

If the patient progresses on that regimen, the combination of encorafenib (Braftovi) and cetuximab (Erbitux) with or without binimetinib (Mektovi) can be used, adds Mizrahi. The recommendation is based on data from the phase III BEACON CRC trial, which showed an improvement in overall survival (OS) with the doublet and triplet versus irinotecan-based chemotherapy in patients with BRAF V600E-mutant mCRC. Because the trial showed equivalent OS data in both of the investigational arms, Mizrahi recommends using the doublet to reduce the toxicity of adding a third drug.