About Index

BRIM-3

"Vemurafenib versus Dacarbazine for Metastatic Melanoma with BRAF V600E Mutation". The New England Journal of Medicine. 2011.

Links to original sources: Wiki Journal Post Full Journal Article

Clinical Question


Does vemurafenib improve overall survival and progression-free survival compared with dacarbazine in patients with previously untreated, metastatic melanoma with the BRAF V600E mutation?

Bottom Line


Vemurafenib significantly improved rates of overall and progression-free survival compared with dacarbazine in patients with previously untreated, metastatic melanoma harboring the BRAF V600E mutation.

Major Points


Patients with metastatic melanoma have historically had a poor prognosis. Vemurafenib, a potent inhibitor of mutated BRAF, was evaluated for its therapeutic impact in patients with the BRAF V600E mutation.

Guidelines


As of the knowledge cutoff for this summary, formal guidelines incorporating vemurafenib's comparative efficacy for the stated patient population have not been specified.

Design


Multicenter, phase 3, randomized, open-label trial.

Population


- 675 patients with previously untreated, unresectable stage IIIC or stage IV melanoma that tested positive for the BRAF V600E mutation. - Inclusion criteria: ≥18 years, ECOG 0 or 1 performance status, sufficient organ function. - Exclusion criteria: Prior cancer within five years, CNS metastases, and other anticancer therapy concurrent use.

Interventions


- Vemurafenib (960 mg orally twice daily) or - Dacarbazine (1000 mg/m² intravenously every 3 weeks).

Outcomes


- Primary outcomes: Rates of overall survival and progression-free survival. - Secondary outcomes: Confirmed response rate and duration of response. - Key results: Vemurafenib had a 63% relative reduction in the risk of death and a 74% reduction in the risk of death or disease progression compared to dacarbazine. - Response rates were 48% for vemurafenib and 5% for dacarbazine. - Median follow-up: 3.8 months for vemurafenib and 2.3 months for dacarbazine groups.

Criticisms


- Overall survival beyond 7 months in either group was not adequately reported due to insufficient follow-up time. - The trial was open-label and not placebo-controlled.

Funding


Hoffmann–La Roche.

Further Reading


Original publication in The New England Journal of Medicine.