Triple-Targeted Therapy With Encorafenib, Binimetinib, and Osimertinib in EGFR-Mutated NSCLC With Acquired BRAF Alteration After Osimertinib: A Single-Center Experience

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Introduction: -mutant metastatic NSCLC who progress on osimertinib and represent a challenging resistance mechanism. Although case series have reported activity with dabrafenib, trametinib, and osimertinib in metastatic NSCLC, there are no published data on the combination of encorafenib, binimetinib, and osimertinib (E+B+O) in this population. Methods: alteration after progression on osimertinib were treated with concurrent E+B+O. Time on therapy, progression-free survival, and overall survival were assessed from the initiation of E+B+O. Response was assessed using Response Evaluation Criteria in Solid Tumors v.1.1. Adverse events were graded using Common Terminology Criteria for Adverse Events v.6.0. Results: G469A variants. One of the five patients achieved a partial response (overall response rate [ORR] 20%) with a duration of response of 32 months and sustained intracranial control. The remaining four patients experienced disease progression. The median time on therapy was 2.0 (range 1.0-39) months, progression-free survival was 2.8 (range 1.7-34) months, and overall survival was 6.6 (range 2.9-39) months. Two patients required dose interruption or discontinuation due to gastrointestinal toxicity (grade 2 diarrhea and grade 3 colitis). No pyrexia was observed. Conclusions: alteration. Larger studies are needed to determine whether E+B+O may be considered in carefully selected patients with close response assessment and monitoring for gastrointestinal toxicity.