Vemurafenib plus cobimetinib in the treatment of mutated metastatic melanoma: the CoBRIM trial. (August 2015)

• Record Type: Journal Article
• Authors: Grimaldi, Antonio M; Simeone, Ester; Ascierto, Paolo A
• Is Part Of: Melanoma management. Volume 2:Number 3(2015)
• Page Start: 209
• Page End: 215
• Publication Date: 2015-08
• Subjects: BRAF inhibitor -- cobimetinib -- combination therapy -- MEK inhibitor -- vemurafenib; Melanoma -- Periodicals; 616.99477005
• DOI: 10.2217/mmt.15.22
• Languages: English
• ISSNs: 2045-0885

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.