In the phase II PHAROS trial reported in the Journal of Clinical Oncology, Gregory J. Riely, MD, PhD, and colleagues found that the combination of encorafenib and binimetinib showed activity in both treatment-naive and previously treated patients with BRAF V600E–mutant metastatic non–small cell lung cancer (NSCLC).
Gregory J. Riely, MD, PhD
Study Details
In the ongoing trial, 98 patients—including 59 treatment-naive and 39 previously treated patients—from sites in five countries were enrolled between June 2019 and June 2022. Patients received encorafenib at 450 mg once daily plus binimetinib a 45 mg twice daily in 28-day cycles until disease progression or unacceptable toxicity. The primary endpoint was confirmed objective response rate on independent radiology review.
Responses
Objective response was observed in 44 (75%, 95% confidence interval [CI] = 62%–85%) of 59 treatment-naive patients, with complete response seen in 9 (15%). An additional 10 patients (17%) had stable disease. Median duration of response was not estimable (95% CI = 23.1 months to not estimable), with 59% and 16% of responses lasing at least 12 and 24 months, respectively.
Among 39 previously treated patients, objective response was observed in 18 (46%, 95% CI = 30%–63%), with complete response seen in 4 (10%). An additional 13 patients (33%) had stable disease. Median duration of response was 16.7 months (95% CI = 7.4 months to not estimable), with 33% and 17% of responses lasting at least 12 and 24 months, respectively.
Median duration of follow-up for progression-free survival was 18.2 months (95% CI = 16.4–22.3 months) among treatment-naive patients and 12.8 months (95% CI = 9.0–19.8 months) among previously treated patients. Median progression-free survival on independent radiology review was not estimable (95% CI = 15.7 months to not estimable) in the treatment-naive group and 9.3 months (95% CI = 6.2 months to not estimable) in the previously treated group. At data cutoff, death had occurred in 17 patients (29%) in the treatment-naive group and in 13 patients (33%) in the previously treated group.
KEY POINTS
- Objective response rates with encorafenib and binimetinib were 75% among treatment-naive patents and 46% among previously treated patients.
- Median durations of response were not estimable and 16.7 months in the two groups, respectively.
Adverse Events
The most common treatment-related adverse events of any grade were nausea (50%), diarrhea (43%), and fatigue (32%). Grade 3 or 4 treatment-related adverse events occurred in 41% of patients (grade 4 in 3%). Treatment-related serious adverse events occurred in 14% of patients, most commonly colitis, in 3%. Treatment-related adverse events led to discontinuation of encorafenib and binimetinib in 15 patients (15%); the most commonly reported treatment-related adverse events were diarrhea, nausea, and vomiting. One patient died from intracranial hemorrhage considered related to treatment.
The investigators concluded, “For patients with treatment-naive and previously treated BRAF V600E–mutant metastatic NSCLC, encorafenib plus binimetinib showed a meaningful clinical benefit with a safety profile consistent with that observed in the approved indication in melanoma.”
Dr. Riely, of Memorial Sloan Kettering Cancer Center, is the corresponding author for the Journal of Clinical Oncology article.
Disclosure: The study was supported by Pfizer. For full disclosures of the study authors, visit ascopubs.org.
