Safety Profile of Encorafenib + Binimetinib and Management of Key Toxicities When Treating Patients with BRAF V600E-Mutant Metastatic NSCLC

Segment V offers a detailed evaluation of the safety and toxicity profile of encorafenib and binimetinib, a central consideration when selecting BRAF/MEK therapy. Dr. Dagogo-Jack outlines the most common adverse events seen in PHAROS, noting that gastrointestinal toxicities (nausea, diarrhea, and vomiting) occurred in approximately 30–50% of patients. Although most events were grade 1–2, they are meaningful because they can significantly impact quality of life, especially in older patients.

She also highlights that transaminase elevations occurred in about 20% of patients, reinforcing the need for routine laboratory monitoring. The presenters contrast the PHAROS regimen with dabrafenib/trametinib, particularly in terms of pyrexia. Historically, fevers occurred in 40–60% of patients on dabrafenib/trametinib, representing one of its most burdensome toxicities. In PHAROS, pyrexia rates were substantially lower (~8%), all grade 1–2, an important differentiator that influenced many clinicians’ preference for encorafenib/binimetinib.

The conversation extends to rate of dose reductions (around 33%) and discontinuations (~15%), emphasizing that while toxicities are common, they are manageable with appropriate monitoring and supportive care. Dr. Rotow notes that the regimen requires additional surveillance not associated with most lung cancer targeted therapies, including cardiac (echo), ophthalmologic, and dermatologic evaluations due to risks of reduced ejection fraction, ocular toxicity, and secondary skin cancers.

Both clinicians highlight the importance of patient counseling prior to initiating therapy. Because patients often assume targeted therapy is always milder than chemotherapy, setting expectations is critical. With proper anticipatory management, the safety profile remains acceptable, and toxicity rarely precludes long-term therapy. This segment underscores that proactive monitoring greatly influences treatment success.