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COLUMBUS Trial: Updated Outcomes With BRAF/MEK Inhibitors in Advanced Melanoma

By: Celeste L. Dixon
Posted: Friday, July 26, 2019

Updated progression-free survival and overall survival results for the combination therapy of encorafenib plus binimetinib from the COLUMBUS trial “continue to represent new benchmarks for combined BRAF/MEK-inhibitor combinations for treatment of BRAF V600‒mutated melanoma,” according to the trial investigators. Keith Flaherty, MD, of the Cancer Center at Massachusetts General Hospital in Boston, and colleagues reported that with a median follow-up of overall survival of 48.6 months across all arms, patients treated with this combination therapy had a median overall survival of 33.6 months versus 23.5 months for those who received encorafenib alone and 16.9 months for those treated with vemurafenib alone.

The combination therapy decreased the risk of death by 39% compared with vemurafenib (hazard ratio = 0.61), the investigators reported at the 2019 American Society for Clinical Oncology (ASCO) Annual Meeting in Chicago (Abstract 9512). Progression-free survival with encorafenib plus binimetinib versus vemurafenib alone was also longer (hazard ratio = 0.52), with updated median progression-free survival rates of 14.9, 9.6, and 7.3 months in the combination, encorafenib, and vemurafenib arms, respectively.

Encorafenib is a highly selective, ATP-competitive BRAF inhibitor, whereas binimetinib is a selective, allosteric, ATP-uncompetitive MEK1/2 inhibitor. Vemurafenib is a BRAF kinase inhibitor.

In the COLUMBUS trial, 577 patients with advanced/metastatic BRAF V600‒mutant melanoma, who were untreated or had experienced disease progression after first-line immunotherapy, were originally randomized 1:1:1 to the three arms. The updated results presented at the ASCO Annual Meeting included an additional 12 months’ follow-up past the data cutoff of the original results.

“[The] incidence of adverse events (all grades) associated with BRAF/MEK inhibitors did not increase substantially with additional 12-month follow-up,” stated the authors. “Adverse events led to discontinuation in 16%, 15%, and 17%, and [to] dose reduction/interruption in 55%, 71%, [and] 62% for [the combination therapy], encorafenib, and vemurafenib, respectively.”

Disclosure: The study authors’ disclosure information may be found at coi.asco.org.



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