Vemurafenib Plus Cobimetinib in the Treatment of Mutated Metastatic Melanoma: The CoBRIM Trial

Abstract

The concomitant inhibition of both BRAF and MEK can produce a more durable and greater tumor response than BRAF monotherapy while reducing BRAF inhibitor-related toxicity. Further evidence of the benefits of combined MEK and BRAF inhibition have been provided by the CoBRIM trial in which median progression-free survival was significantly increased with vemurafenib plus cobimetinib compared with vemurafenib alone (9.9 vs 6.2 months; hazard ratio for death or progression: 0.51; 95% CI: 0.39–0.68; p < 0.001) in 495 patients with advanced BRAF-mutated melanoma. Overall survival data in the CoBRIM trial were immature at time of final progression-free survival analysis but showed an hazard ratio for death of 0.65 (95% CI: 0.42–1.00; p = 0.046; boundary p < 0.0000037). Combination therapy was well tolerated with a reduced incidence of cutaneous squamous-cell carcinoma/keratoacanthoma. This combination may be a starting point for novel combination strategies with immunotherapies and other targeted therapies.

KEYWORDS :

• BRAF inhibitor
• cobimetinib
• combination therapy
• MEK inhibitor
• vemurafenib

Financial competing interests disclosure

PA Ascierto had/has a consultant/advisory role for Bristol-Myers Squibb, Roche-Genentech, Merck Sharp & Dohme, GlaxoSmithKline, Ventana and Novartis. He received research funds from Bristol-Myers Squibb and Ventana. He also receive honoraria from Bristol-Myers Squibb, Roche-Genentech, GlaxoSmithKline. AM Grimaldi and E Simeone received honoraria from Bristol-Myers Squibb, GlaxoSmithKline and Novartis. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

Additional information

Funding

PA Ascierto had/has a consultant/advisory role for Bristol-Myers Squibb, Roche-Genentech, Merck Sharp & Dohme, GlaxoSmithKline, Ventana and Novartis. He received research funds from Bristol-Myers Squibb and Ventana. He also receive honoraria from Bristol-Myers Squibb, Roche-Genentech, GlaxoSmithKline. AM Grimaldi and E Simeone received honoraria from Bristol-Myers Squibb, GlaxoSmithKline and Novartis. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed