COLUMBUS Trial 5-Year Update: Encorafenib/Binimetinib vs Vemurafenib or Encorafenib in Advanced BRAF V600–Mutant Melanoma

Get Permission

In a 5-year update of part 1 of the phase III COLUMBUS trial reported in the Journal of Clinical Oncology, Dummer et al found a continued benefit of encorafenib plus binimetinib vs vemurafenib in patients with advanced BRAF V600–mutant melanoma. The trial supported the June 2018 approval of encorafenib plus binimetinib in this setting. 

Study Details

In the open-label international trial, 577 patients with locally advanced unresectable or metastatic disease who were previously untreated or had disease progression after first-line immunotherapy were randomly assigned 1:1:1 between December 2013 and April 2015 to receive encorafenib at 450 mg once daily plus binimetinib at 45 mg twice daily (n = 192); vemurafenib at 960 mg twice daily (n = 191), or encorafenib at 300 mg once daily (n = 194). The primary endpoint was progression-free survival.

At primary analysis, median progression-free survival was 14.9 months in the encorafenib/binimetinib group vs 7.3 months in the vemurafenib group (hazard ratio [HR] = 0.51, 95% confidence interval [CI] = 0.39–0.67). Analysis at a median follow-up of 48.8 months found median overall survival was 33.6 vs 16.9 months (HR = 0.61, 95% CI = 0.48–0.79). The current analysis was performed at 65 months after the last patient was randomly assigned.

Key Findings

Progression-free survival at 5 years was 23% in the encorafenib/binimetinib group, 10% in the vemurafenib group, and 19% in the encorafenib group. Among patients with normal lactate dehydrogenase (LDH) levels, rates were 31% in the encorafenib/binimetinib group and 12% in the vemurafenib group. After study treatment, 50% of the encorafenib/binimetinib group, 69% of the vemurafenib group, and 62% of the encorafenib group received subsequent systemic treatments.

Overall survival at 5 years was 35% in the encorafenib/binimetinib group, 21% in the vemurafenib group, and 35% in the encorafenib group. Among patients with normal LDH levels, rates were 45% in the encorafenib/binimetinib group and 28% in the vemurafenib group. 

Median follow-up for overall survival was 70.4 months. Median overall survival was 33.6 months (95% CI = 24.4–39.2 months) in the encorafenib/binimetinib group (HR vs vemurafenib = 0.64, 95% CI = 0.50–0.81; HR vs encorafenib = 0.93, 95% CI = 0.72–1.19), 16.9 months (95% CI = 14.0–24.5 months) in the vemurafenib group, and 23.5 months (95% CI = 19.6–33.6 months) in the encorafenib group (HR vs vemurafenib = 0.71, 95% CI = 0.56–0.91).

No new safety concerns emerged with long-term follow-up, and findings were consistent with the known tolerability profile of encorafenib plus binimetinib. Overall, 16% to 18% of patients across treatment groups discontinued study treatment due to adverse events.

The investigators concluded: “In this 5-year update of part 1 of the COLUMBUS trial, encorafenib plus binimetinib treatment demonstrated continued long-term benefits and a consistent safety profile in patients with BRAF V600–mutant melanoma.”

Reinhard Dummer, MD, of the Department of Dermatology, University Hospital Zurich, is the corresponding author for the Journal of Clinical Oncology article.

Disclosure: The trial was sponsored by Array BioPharma, which was acquired by Pfizer in July 2019. For full disclosures of the study authors, visit

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.