The BRAF inhibitor vemurafenib induced clinical responses in more than half of patients with previously treated V600–mutant metastatic melanoma, according to study results published in The New England Journal of Medicine.
Based on earlier phase 1 trials indicating that vemurafenib (Zelboraf, Hoffmann-La Roche) produced tumor regressions in patients with BRAF V600-mutant metastatic melanoma, researchers designed a multicenter, phase 2 trial to investigate the efficacy of vemurafenib with respect to overall response rate, duration of response and OS.
The study enrolled 132 patients who received oral vemurafenib 960 mg twice daily until the disease progressed or unacceptable toxic effects developed. Patients with disease progression were permitted to continue treatment if the investigator determined that the patient would benefit clinically.
According to study results, 53% of patients exhibited a confirmed overall response (95% CI, 44-62), with 6% exhibiting a complete response and 47% exhibiting a partial response. The median duration of response was 6.7 months (95% CI, 5.6-8.6), and the median PFS was 6.8 months (95% CI, 5.6-8.1). The median OS was 15.9 months (95% CI, 11.6-18.3).
“This study shows that [vemurafenib] changes the natural history of this disease,” researcher Antoni Ribas, MD, PhD, of UCLA’s Jonsson Comprehensive Cancer Center, said in a press release. “This data is beyond what I would have expected. We’re seeing a significant number of patients with durable responses to the drug, and that the whole group of treated patients is living longer. These results tell us that this drug is having a very big impact, and this changes the way we treat metastatic melanoma.”
The most common adverse events included alopecia, fatigue, grade-1 or -2 arthralgia, rash and photosensitivity. Cutaneous squamous cell carcinomas were diagnosed in 26% of patients.
“While the problem of relapse and resistance is great, this study provides evidence that, in some patients, their melanoma is controlled for over 2 years on the medication,” researcher Jeffrey A. Sosman, MD, of the Vanderbilt-Ingram Cancer Center, said in a press release.
Tony Talebi, MD