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

This segment explores why multiple efficacy endpoints are essential when evaluating targeted therapies and transitions into a discussion of safety outcomes from the PHAROS study. The speakers emphasize that response rate, PFS, and OS each capture different but complementary aspects of clinical benefit. Response rate is particularly critical for patients with high disease burden or significant symptoms, where achieving rapid tumor shrinkage may prevent early clinical deterioration and preserve the opportunity for subsequent therapies. PFS and duration of response are especially informative in single-arm studies, as they are less affected by differences in subsequent treatments, geography, or timing of trial enrollment. OS remains the most meaningful endpoint for patients, reflecting both length and quality of life.

The discussion also highlights the importance of contextualizing survival outcomes, given that earlier BRAF-MEK trials were conducted in the pre-immunotherapy era, whereas patients in PHAROS may have had access to additional effective therapies that influence OS. Long-term follow-up is therefore critical.

The conversation then turns to safety, a major consideration for BRAF-MEK combinations, particularly in an older population with more comorbidities. Encorafenib and binimetinib showed a safety profile consistent with the drug class, dominated by gastrointestinal toxicities such as nausea, diarrhea, and vomiting, mostly low grade. Liver enzyme elevations were observed in about 20% of patients. Notably, pyrexia occurred far less frequently than with older regimens. One-third of patients required dose reductions, and 15% discontinued therapy due to toxicity.