Roche announces phase III study results of Zelboraf for adjuvant treatment of BRAF V600 mutation-positive melanoma
Roche today announced data for the phase III BRIM8 study, which was designed to investigate the efficacy and safety of Zelboraf (vemurafenib) in the adjuvant (after surgery) treatment of people with completely resected, BRAF V600 mutation-positive melanoma. The study assessed two cohorts; stage IIC-IIIB (cohort 1) and stage IIIC (cohort 2) melanoma patients. The study did not meet its primary endpoint of significantly reducing the risk of recurrence (disease-free survival; DFS) in patients with stage IIIC melanoma (cohort 2); however, a 46% reduction in recurrence risk was observed in stage IIC-IIIB patients (cohort 1). The safety profile was consistent with that seen in previous studies of Zelboraf in advanced melanoma.
- People in cohort 2 had a median DFS of 23.1 months with Zelboraf vs. 15.4 months with placebo (HR=0.80; 95% CI 0.54-1.18, p=0.2598).
- For people in cohort 1, median DFS was not reached with Zelboraf compared with median DFS of 36.9 months with placebo, (HR=0.54; 95% CI 0.37-0.79). Due to the pre-specified statistical design of the study, the results for cohort 1 cannot be formally tested for significance.
“While results in people with stage IIIC melanoma were not what we had hoped, the reduction in the risk of recurrence in people with stage IIC-IIIB disease is encouraging and suggests Zelboraf may play a role in this earlier setting,” said Sandra Horning, MD, Roche’s Chief Medical Officer and Head of Global Product Development.
Full data will be presented today at the European Society of Medical Oncology (ESMO) annual meeting in Madrid, Spain as part of Presidential Symposium III (Abstract #LBA7) from 4.30pm to 5.45pm CET.
The results will also be featured in ESMO’s official press program.
BRIM8 is a multicentre, randomized, double-blind, two-cohort, placebo-controlled study that investigated the efficacy and safety profile of Zelboraf for the adjuvant treatment of people with completely resected, BRAF V600 mutation-positive melanoma at high risk for recurrence. The primary endpoint was disease-free survival. The study had a Special Protocol Assessment and was designed with two cohorts with a hierarchical analysis where cohort 2 was required to meet the primary endpoint before cohort 1 analysis. People in cohort 1 had completely resected Stage IIC, IIIA or IIIB melanoma; people in cohort 2 had completely resected Stage IIIC melanoma. In the study, 498 people were randomised to receive either oral Zelboraf 960mg or placebo twice daily for 52 weeks.
Melanoma is less common, but more aggressive and deadlier than other forms of skin cancer.1,2 BRAF is mutated in approximately half of melanomas.3 More than 232,000 people worldwide are currently diagnosed with melanoma each year.4 In recent years, there have been significant advances in treatment for metastatic melanoma and people with the disease have more options. However, it continues to be a serious health issue with a high unmet need and a steadily increasing incidence over the past 30 years.5