Dr Langer on Encorafenib Plus Binimetinib in BRAF V600E–Mutant NSCLC

Corey J. Langer, MD, director, Thoracic Oncology, Penn Medicine, professor, medicine (hematology-oncology), the Hospital of the University of Pennsylvania, discusses findings from the ongoing phase 2 PHAROS trial (NCT03915951) in patients with non–small cell lung cancer (NSCLC) harboring BRAF V600E mutations.

At the 2023 ASCO Annual Meeting, Gregory J. Riely, MD, of Memorial Sloan Kettering Cancer Center, presented data with a novel combination of encorafenib (Braftovi), a BRAF inhibitor, and binimetinib (Mektovi), a MEK inhibitor, in patients with BRAF V600E–mutant NSCLC. PHAROS enrolled patients with an ECOG performance status of 0 or 1 who had received up to 1 prior line of therapy for metastatic NSCLC. Patients with additional actionable mutations such as EGFR mutations, ALK fusions, or ROS1 rearrangements were excluded. Patients with asymptomatic brain metastases were allowed. In this trial, patients received encorafenib at 450 mg daily plus binimetinib at 45 mg twice daily in 28-day cycles.

The objective response rates were 75% (95% CI, 62%-85%) in the treatment-naïve cohort (n = 59) and 46% (95% CI, 30%-63%) in the previously treated cohort (n = 39). At the data cutoff date, the median duration of response (DOR) was not evaluable (NE) in the treatment-naïve cohort (95% CI, 23.1 months-NE). In the previously treated cohort, the median DOR was 16.7 months (95% CI, 7.4-NE).

The 24-week disease control rates were 64% (95% CI, 51%-76%) in the treatment-naïve cohort, including patients with stable disease, and 41% (95% CI, 26%-58%) in the previously treated cohort. Nine and 4 patients in the treatment-naïve and previously treated cohorts, respectively, achieved complete responses. The median progression-free survival was NE (95% CI, 15.7 months-NE) and 9.3 months (95% CI, 6.2-NE) in the treatment-naïve and previously treated cohorts, respectively. These data indicate the potential for improved efficacy with encorafenib plus binimetinib compared with standard dabrafenib (Tafinlar) plus trametinib (Mekinist), which is FDA approved for patients with BRAF V600E–mutant unresectable or metastatic solid tumors.

Although encorafenib plus binimetinib is not yet approved for patients in this population, it may receive approval in the future, Langer says. On April 4, 2023, the FDA accepted a supplemental new drug application for the combination for patients with NSCLC harboring a BRAF V600E mutation. Since BRAF V600E mutations affect a small population of patients with NSCLC, conducting phase 3 trials in these patients is challenging, Langer concludes.