BRIM-3
Trial question
What is the effect of vemurafenib in patients with metastatic melanoma with BRAF V600E mutation?
Study design
Multi-center
Open label
RCT
Population
Characteristics of study participants
44.0% female
56.0% male
N = 675
675 patients (294 female, 381 male).
Inclusion criteria: patients with previously untreated, metastatic melanoma with BRAF V600E mutation.
Key exclusion criteria: history of cancer within the past 5 years or metastases to the CNS, unless such metastases had been definitively treated > 3 months previously with no progression and no requirement for continued corticosteroid therapy, and concomitant treatment with any other anticancer therapy.
Interventions
N=337 vemurafenib (at a dose of 960 mg BID PO).
N=338 dacarbazine (at a dose of 1,000 mg per square meter of body-surface area by intravenous infusion every 3 weeks).
Primary outcome
Overall survival at 6 months
84%
64%
84.0 %
63.0 %
42.0 %
21.0 %
0.0 %
Vemurafenib
Dacarbazine
Significant
increase ▲
NNT = 5
Significant increase in overall survival at 6 months (84% vs. 64%).
Secondary outcomes
Significant decrease in progression-free survival (5.3 months vs. 1.6 months; HR 0.26, 95% CI 0.2 to 0.33).
Significant increase in response rate (48% vs. 5%; AD 43%, 95% CI 17.49 to 68.51).
Safety outcomes
No significant difference in fatigue and vomiting.
Significant differences in adverse events leading to dose modification/interruption (38% vs. 16%), arthralgia (21% vs. 1%), rash (18% vs. 0%), SCC (12% vs. < 1%), keratoacanthoma (8% vs. 0%), and alopecia (8% vs. 0%).
Conclusion
In patients with previously untreated, metastatic melanoma with BRAF V600E mutation, vemurafenib was superior to dacarbazine with respect to overall survival at 6 months.
Reference
Chapman PB, Hauschild A, Robert C et al. Improved survival with vemurafenib in melanoma with BRAF V600E mutation. N Engl J Med. 2011 Jun 30;364(26):2507-16.
Open reference URL