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Vemurafenib extended survival in BRAF V600-positive melanoma
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Patients with advanced BRAF V600E- and BRAF V600K-positive melanoma treated with vemurafenib experienced longer OS and PFS than those treated with dacarbazine, according to extended follow-up of the BRIM-3 trial.
BRIM-3 — a phase 3, randomized, open-label study — included 675 patients with treatment-naive, BRAF V600-positive metastatic melanoma. All patients were aged older than 18 years, with an ECOG performance status of 0 or 1 and a life expectancy of at least 3 months.
Axel Hauschild
Axel Hauschild, MD, professor of dermatology at University Hospital in Kiel, Germany, and colleagues randomly assigned 337 patients to vemurafenib (Zelboraf, Genentech) 960 mg orally twice daily. The other 338 patients received dacarbazine 1,000 mg/m2 intravenously every 3 weeks.
OS and PFS served as co-primary endpoints.
Initial results showed vemurafenib was associated with a reduced risk for death and progression in patients with advanced BRAF V600 mutation-positive melanoma.
In the follow-up analysis, researchers evaluated outcomes in the BRAF V600E and BRAF V600K subgroups.
Median follow-up was 12.5 months for patients assigned vemurafenib and 9.5 months among those assigned dacarbazine. Twenty-five percent of patients initially assigned to dacarbazine crossed over to vemurafenib.
Researchers reported longer median OS (13.6 months vs. 9.7 months; HR=0.7; 95% CI, 0·57-0·87) and median PFS (6.9 months vs. 1.6 months; HR=0.38; 95% CI, 0.32-0.46) in the vemurafenib arm.
Among patients with a BRAFV600E mutation (n=598), median OS was 13.3 months for those in the vemurafenib arm vs. 10 months for those in the dacarbazine arm (HR=0.75; 95% CI, 0.6-0.93). Median PFS was 6.9 months in the vemurafenib arm vs. 1.6 months in the dacarbazine arm (HR=0.39; 95% CI, 0.33-0.47).
Among patients with a BRAF V600K mutation (n=57), median OS was 14.5 months in the vemurafenib arm vs. 7.6 months for the dacarbazine arm (HR=0.43; 95% CI, 0.21-0.9). Median PFS was 5.9 months in the vemurafenib arm vs. 1.7 months in the dacarbazine arm (HR=0.3; 95% CI, 0.16-0.56).
The most common grade 3 or grade 4 adverse events in the vemurafenib arm were cutaneous squamous cell carcinoma (19%) and keratoacanthomas (10%), rash (9%) and abnormal liver function tests (11%). The most common grade 3 or grade 4 adverse events in the dacarbazine group was neutropenia (9%). Grade 5 events occurred in eight (2%) patients assigned vemurafenib and seven (2%) patients assigned dacarbazine.
Disclosure: The study was funded by F Hoffmann-La Roche-Genentech.
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