Encorafenib Plus Binimetinib Exhibited Clinical Efficacy and Safety Among Patients With BRAFV600E-Mutant Metastatic NSCLC

Primary Analysis Results From the PHAROS Study 

Findings from the primary analysis of the phase 2 PHAROS study show that combined treatment with the BRAF inhibitor encorafenib and the MEK inhibitor binimetinib exhibited meaningful clinical efficacy with acceptable safety among patients with either treatment-naïve or previously-treated BRAF^V600E-mutant metastatic non-small cell lung cancer (NSCLC). 

According to Gregory Riely, MD, PhD, Memorial Sloan Kettering Cancer Center, New York, New York, and coauthors, “dabrafenib plus trametinib is a standard treatment in patients with BRAF^V600E-mutant metastatic NSCLC,” but “given the observed efficacy and safety profile of encorafenib plus binimetinib in patients with BRAF^V600-mutant metastatic melanoma this combination therapy was assessed in this phase 2 trial in patients with BRAFV600E-mutant metastatic NSCLC.”

There were a total of 98 patients with BRAF^V600E-mutant metastatic NSCLC enrolled in this trial, 59 with treatment-naïve and 39 with previously-treated disease. All patients received 450 mg encorafenib once daily plus 45 mg binimetinib twice daily, in 28-day cycles. Tumor measurements were assessed every 8 weeks for a duration of 12 months, followed by additional measurements every 12 weeks until disease progression or study conclusion. The primary end point of this study was objective response rate (ORR) confirmed by independent radiology review (IRR). Key secondary end points included duration of response (DOR), disease control rate (DCR), progression-free survival (PFS), overall survival (OS), time to response, and safety.

At the data cutoff point, median treatment duration was 9.2 months with encorafenib and 8.4 months with binimetinib. As determined by IRR, the ORR was 75% among treatment-naïve patients and 46% among previously-treated patients. After 24 weeks, DCR was 64% among treatment-naïve patients and 41% among previously-treated patients. Median DOR and PFS were not estimable in treatment-naïve patients, however previously-treated patients experienced a median DOR of 16.7 months (95% CI, 7.4 to NE) and a median PFS of 9.3 months (95% CI, 6.2 to NE).

The safety profile of encorafenib plus binimetinib was consistent with that observed in the approved indication in melanoma. The most common treatment-related adverse events included nausea (50%), diarrhea (43%), and fatigue (32%). Treatment-related adverse events led to dose reductions in 24 patients (24%) and permanent discontinuation in 15 patients (15%). There was 1 grade 5 treatment-related adverse event, of intracranial hemorrhage.

Dr Riely et al concluded, “encorafenib plus binimetinib represents a potential new treatment option for patients with BRAF^V600E-mutant metastatic NSCLC.”

Source: 

Riely G, Smit EF, Ahn MJ, et al. Phase II, open-label study of encorafenib plus binimetinib in patients with BRAFV600-mutant metastatic non–small-cell lung cancer. J of Clin Oncol. Published online June 4, 2023. doi:10.1200/JCO.23.00774