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Cobimetinib plus vemurafenib extended PFS in BRAF V600-mutated metastatic melanoma
The addition of cobimetinib to vemurafenib significantly prolonged PFS yet increased toxicity among patients with BRAF V600-mutated melanoma, according to phase 3 study results presented at the European Society of Medical Oncology Annual Congress in Madrid.
Antoni Ribas, MD, PhD, professor of medicine at the David Geffen School of Medicine at the University of California in Los Angeles, and colleagues evaluated data from 495 patients with unresectable locally advanced or metastatic BRAF V600-mutated melanoma. All patients were previously untreated.
Antoni Ribas
Researchers assigned 247 patients to BRAF inhibition with vemurafenib (Zelboraf; Genentech, Daiichi Sankyo) plus MEK inhibition with cobimetinib (GDC-0973/XL518, Exelixis. The other 248 patients received vemurafenib plus placebo.
Overall, patients who received the combination experienced significantly prolonged median PFS (9.9 months vs. 6.2 months; HR=0.51; 95% CI, 0.39-0.68).
Researchers reported higher rates of response (68% vs. 45%; P<.001) and complete response (10% vs. 4%) in the combination arm.
At an interim analysis, 81% of patients (95% CI, 75-87) assigned vemurafenib plus cobimetinib achieved 9-month OS, compared with 73% of patients (95% CI, 65-80) in the control arm.
More patients assigned the combination experienced a grade ≥3 adverse event (65% vs. 59%). However, fewer patients assigned the combination experienced a secondary cutaneous cancer (grade 3, 2% vs. 11%), incidence of which had been increased in trials that assessed vemurafenib alone.
The rate of study treatment discontinuation was similar between the arms (12% in the control arm vs. 13% in the combination arm).
“The combination of vemurafenib and cobimetinib, as compared with vemurafenib alone, resulted in an improvement in PFS and objective responses, with early evidence of improved OS and a somewhat increased toxicity profile, among patients with advanced BRAF-mutated melanoma,” Ribas and colleagues concluded.
Disclosure: The study was funded in by F. Hoffmann-La Roche/Genentech. See the study for a full list of the researchers’ relevant financial disclosures.