Encorafenib plus binimetinib can provide long-term benefits in patients with BRAF V600-mutant melanoma, according to research published in the Journal of Clinical Oncology.
A 5-year update from the COLUMBUS trial showed longer progression-free survival (PFS) and overall survival (OS) for patients who received encorafenib plus binimetinib, compared with those who received vemurafenib.
The combination also improved PFS when compared with encorafenib alone, but OS outcomes were similar between the combination and encorafenib monotherapy arms.
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The phase 3 COLUMBUS trial (ClinicalTrials.gov identifier: NCT01909453) enrolled 577 patients with locally advanced unresectable or metastatic BRAF V600-mutant melanoma who were treatment-naïve or had first-line therapy failure at baseline.
Patients were randomly assigned to receive 450 mg of encorafenib once daily plus 45 mg of binimetinib twice daily (n=192), 960 mg of vemurafenib twice daily (n=191), or 300 mg of encorafenib once daily (n=194).
At the data cutoff, 13.0% of patients in the combination arm, 2.1% in the vemurafenib arm, and 6.2% in the encorafenib arm remained on therapy. The primary reason for discontinuation was progressive disease for 55.2%, 59.7%, and 53.6% of patients, respectively.
At a median follow-up of 40.8 months, the median PFS was significantly longer in the combination arm than in the vemurafenib arm (hazard ratio [HR], 0.51; 95% CI, 0.40-0.67) or the encorafenib arm (HR, 0.79; 95% CI, 0.61-1.02).
The median PFS was 14.9 months in the combination arm, 7.3 months in the vemurafenib arm, and 9.6 months in the encorafenib arm. The 5-year PFS rate was 23% in the combination arm, 10% in the vemurafenib arm, and 19% in the encorafenib arm.
The trial was not powered for OS comparisons between the treatment arms. However, the median OS was significantly longer in the combination arm than in the vemurafenib arm (HR, 0.64; 95% CI, 0.50-0.81). The difference between the combination arm and the encorafenib arm was not significant (HR, 0.93; 95% CI, 0.72-1.19).
At a median follow-up of 70.4 months, the median OS was 33.6 months in the combination arm, 16.9 months in the vemurafenib arm, and 23.5 months in the encorafenib arm. The 5-year OS rate was 35% in the combination arm, 21% in the vemurafenib arm, and 35% in the encorafenib arm.
The incidence of grade 3-4 adverse events was 70% in the combination arm, 66% in the vemurafenib arm, and 70% in the encorafenib arm. Adverse events led to dose adjustments or interruptions in 56%, 62%, and 72% of patients, respectively.
“The safety profile observed with a longer follow-up was consistent with previous observations, and the burden of toxicity with encorafenib plus binimetinib treatment decreased over time,” the researchers wrote. “These data demonstrate the long-term benefits of encorafenib plus binimetinib in patients with unresectable or metastatic BRAF V600–mutant melanoma.”
Disclosures: This research was supported by Pfizer. Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of disclosures.
Reference
Dummer R, Flaherty KT, Robert C, et al. COLUMBUS 5-year update: A randomized, open-label, phase III trial of encorafenib plus binimetinib versus vemurafenib or encorafenib in patients with BRAF V600–mutant melanoma. J Clin Oncol. Published online July 21, 2022. doi:10.1200/JCO.21.02659
