On October 11, the U.S. Food and Drug Administration (FDA) approved the BRAF inhibitor encorafenib (Braftovi) with the MEK inhibitor binimetinib (Mektovi) for adult patients with metastatic non–small cell lung cancer (NSCLC) and a BRAF V600E mutation, as detected by an FDA-approved test.
The FDA also approved the FoundationOne CDx (tissue) and FoundationOne Liquid CDx (plasma) as companion diagnostics for encorafenib with binimetinib. If no mutation is detected in a plasma specimen, the tumor tissue should be tested.
PHAROS Trial
Efficacy was evaluated in 98 patients with metastatic BRAF V600E–mutated NSCLC enrolled in PHAROS (ClinicalTrials.gov identifier NCT03915951), an open-label, multicenter, single-arm study. Receipt of prior BRAF or MEK inhibitors was not allowed. Patients received encorafenib and binimetinib until disease progression or unacceptable toxicity.
The major efficacy outcome measures were objective response rate per Response Evaluation Criteria in Solid Tumors version 1.1, and duration of response as assessed by an independent review committee. Among 59 treatment-naive patients, objective response rate was 75% (95% confidence interval [CI] = 62%–85%); median duration of response was not estimable (95% CI = 23.1 months to not estimable). Among 39 previously treated patients, objective response rate was 46% (95% CI = 30%–63%) with a median duration of response of 16.7 months (95% CI = 7.4 months to not estimable).
The most common adverse reactions (≥ 25%) were fatigue, nausea, diarrhea, musculoskeletal pain, vomiting, abdominal pain, visual impairment, constipation, dyspnea, rash, and cough.
The recommended doses of the agents for patients with BRAF V600E mutation–positive NSCLC are encorafenib at 450 mg orally once daily and binimetinib at 45 mg orally twice daily.
This review used the Assessment Aid, a voluntary submission from the applicant to facilitate the FDA’s assessment. This application was granted Orphan Drug designation.
