The anticipated results of the COLUMBUS trial were recently published in The Lancet Oncology.
Reinhard Dummer, from University Hospital Zürich in Switzerland, and colleagues looked to investigate the benefit of a new BRAF inhibitor plus MEK inhibitor combination in first-line metastatic BRAF-mutated melanoma compared with BRAF inhibitor monotherapy, the standard when the clinical trial started recruitment.
As anticipated the combined modality arm of encorafenib plus binimetinib was associated with an improved efficacy profile compared with encorafenib or vemurafenib monotherapy, and the combination also has an attractive tolerability profile different from the other two BRAF and MEK inhibitor combinations already approved for the treatment of BRAF-mutated metastatic melanoma.
Identifying novel and effective therapeutic regimens in patients with metastatic melanoma is challenging in light of the currently available therapeutic options based either on immunotherapy or BRAF and MEK inhibitor combinations. The rationale for encorafenib plus binimetinib therapy exists and is supported by preliminary evidence from earlier trials suggesting that especially encorafenib is a more selective BRAF inhibitor than others in the drug class and it may translate into a better clinical outcome for patients receiving this treatment option.
Using progression-free survival as a primary endpoint for front-line therapies in this disease may be insufficient for evaluating the real clinical benefit as the real value in metastatic melanoma is to prolong survival in this setting. The main question with the combination of encorafenib plus binimetinib is whether this combination will offer a major benefit in overall survival (OS) compared with the 24 months given by other approved BRAF–MEK inhibitor combinations.
A press release published in February 2018 by Array BioPharma Inc and Pierre Fabre announced that the combination of encorafenib plus binimetinib shows a median OS of 33.6 months for patients treated with the combination, compared with 16.9 months for patients treated with vemurafenib as a monotherapy. These results will completely be presented at ASCO in June 2018 and may identify encorafenib plus binimetinib as the new treatment option for first-line BRAF-mutated metastatic melanoma.