Date: 2011-06-05
Type of information:
phase: 3
Announcement: results
Company: Roche (Switzerland)
Product: vemurafenib
Action mechanism: specific inhibition of the activity of the mutant BRAF protein that is found in approximately half of all cases of melanoma
Disease: metastatic melanoma
Therapeutic area: Cancer - Oncology
Country:
Trial
details: BRIM3 (Study NO25026) is a global, randomised, open-label, controlled, multicentre, Phase III study that compared vemurafenib to dacarbazine chemotherapy, a current standard of care, in 675 patients with previously untreated BRAF V600 mutation-positive, unresected locally advanced or metastatic melanoma. Co-primary endpoints were OS and PFS. Secondary endpoints included response rate, response duration and safety profile.
BRIM2 (Study NP22657) is a global, single-arm, multicentre, open-label Phase II study that enrolled 132 patients with previously treated BRAF V600 mutation-positive metastatic melanoma. Unlike BRIM3, BRIM2 enrolled people who have previously received a treatment for metastatic melanoma. The primary endpoint of the study was best overall response rate and the updated data showed that 53 percent of patients had tumour shrinkage (median duration of response = 6.7 months). People who participated in BRIM2 also lived a median of 6.7 months without their disease getting worse (median PFS). Median OS has not yet been reached after a median follow-up of 10 months.
Latest
news: Roche has announced that a Phase III study (BRIM3) showed vemurafenib (RG7204, PLX4032) significantly improved overall survival in people with previously untreated BRAF V600 mutation-positive metastatic melanoma, compared to chemotherapy. In the study, the risk of death was reduced by 63 percent for people who received vemurafenib compared to those who received chemotherapy (hazard ratio [HR]=0.37, p<0.0001). In addition, vemurafenib significantly reduced the risk of the disease getting worse (progression-free survival, or PFS, a co-primary endpoint), by 74 percent compared to chemotherapy (HR=0.26, p<0.0001). The safety profile of vemurafenib was consistent with previous clinical studies. People were enrolled into the study based on BRAF mutation status as determined by the cobas 4800 BRAF V600 Mutation Test, an investigational diagnostic from Roche.
The response rate (those who experienced tumour shrinkage) in the group of patients who received vemurafenib (48.4 percent) was nearly nine times higher than in the group who received chemotherapy (5.5 percent, p<0.0001). After six months, 84 percent of patients who received vemurafenib were alive compared to 64 percent who received chemotherapy.
The improvement in overall survival, PFS and tumour shrinkage with vemurafenib was seen in patients regardless of age, gender, or disease risk factor.
In January 2011, an independent data monitoring board reviewed data from a planned interim analysis of BRIM3 and recommended the release of study results due to compelling efficacy. The board also recommended that patients in the chemotherapy arm be permitted to crossover or receive vemurafenib instead of chemotherapy.
The median length of time patients lived (median OS) cannot be reliably estimated at this time because of the small number of patients in long-term follow-up. Median OS estimates when BRIM3 met this co-primary endpoint in January 2011 were 9.2 months in patients receiving vemurafenib and 7.8 months in those receiving chemotherapy; an additional two months of follow-up showed an estimated median OS of 10.5 months for patients receiving vemurafenib, while the median OS estimate for patients receiving chemotherapy remained at 7.8 months.
