Phase III Results of Adjuvant Vemurafenib in BRAF V600–Mutated Melanoma
Posted: Thursday, May 17, 2018
The use of systemic adjuvant vemurafenib monotherapy in resected BRAF V600–mutated melanoma was explored in the international phase III BRIM8 trial, reported in The Lancet Oncology. Although notable increases in disease-free survival were observed in patients with stages IIC, IIIA, and IIIB melanoma, the primary endpoint of disease-free survival in those with resected stage IIIC disease was not met. Michele Maio, MD, PhD, of the University Hospital of Siena, Italy, and colleagues concluded that “1 year of adjuvant vemurafenib might not be an optimal treatment regimen in this patient population.”
The randomized double-blind trial enrolled nearly 500 patients in 2 cohorts. In cohort 2 (for which hierarchical analysis was prespecified to occur before cohort 1), 93 and 91 patients were assigned to vemurafenib and placebo, respectively; in cohort 1, 157 patients were assigned to receive vemurafenib and 157 patients, placebo.
After a median follow-up of 33.5 months in cohort 2, the median disease-free survival was 23.1 months for vemurafenib versus 15.4 months for placebo (P = .26). For cohort 1, after a median follow-up of 30.8 months, the median disease-free survival for the vemurafenib group was not reached, whereas it was 36.9 months for the placebo group. But, due to the trial’s structure, the resulting log-rank P value of .001 could not be considered significant.
As for toxicity, grade 3/4 adverse events occurred in more than half of the patients treated with vemurafenib, including keratoacanthoma, arthralgia, squamous cell carcinoma, and elevated levels of alanine aminotransferase. Serious adverse events were reported in 16% of those treated with vemurafenib, compared with 10% of those treated with placebo.