Vemurafenib adjuvant therapy does not improve disease-free survival (DFS) among patients with resected stage IIC to IIIB melanoma, according to findings published in The Lancet Oncology.
The standard of care for patients with stage II to III melanoma is surgical resection, but despite successful treatment, patients face high rates of disease recurrence and death. Clinical studies exploring potential adjuvant therapies have demonstrated efficacy but also substantial toxicity; further investigation for safe and effective adjuvant therapy is necessary for this patient population.
For this double-blind phase 3 study, researchers randomly assigned 498 patients with stage IIC-IIIA-IIIB (cohort 1) or stage IIIC (cohort 2) BRAFV600 mutation-positive melanoma who had undergone complete resection to receive vemurafenib 960 mg twice daily or placebo for 1 year. Three-hundred and fourteen patients were enrolled in cohort 1 and 184 patients to cohort 2. The median follow-up was 30.8 months in cohort 1 and 33.5 months in cohort 2.
Median DFS was 23.1 months among patients in the vemurafenib arm vs 15.4 months in the placebo arm in cohort 2. DFS was not evaluable for patients treated with vemurafenib compared with 36.9 months for patients treated with placebo in cohort 1. Neither arm met the prespecified requirements for significance.
Grade 3 to 4 adverse events occurred in 57% and 15% of patients in the vemurafenib and placebo arms, respectively. The most frequently observed grade 3 to 4 AE in the vemurafenib arm included keratoacanthoma, arthralgia, squamous cell carcinoma, rash, and elevated alanine aminotransferase.
The authors concluded that “1 year of adjuvant vemurafenib was well tolerated, but might not be an optimal treatment regimen in this patient population.”
Maio M, Lewis K, Demidov L, et al. Adjuvant vemurafenib in resected, BRAFV600 mutation-positive melanoma (BRIM8): a randomised, double-blind, placebo-controlled, multicentre, phase 3 trial [published online February 21, 2018]. Lancet Oncol. doi: 10.1016/S1470-2045(18)30106-2