Patients with BRAF V600-mutant metastatic melanoma who were treated with vemurafenib demonstrated significantly improved OS compared with patients who received dacarbazine, according to an updated analysis of a phase 3 trial presented at the Society for Melanoma Research 2013 Congress.
Data from the original analysis of the BRIM-3 trial indicated vemurafenib (Zelboraf, Hoffmann-La Roche) reduced the risk for death and disease progression (P˂.001).
The current, extended analysis includes data on patients who initially were assigned to dacarbazine (DTIC) but crossed over to treatment with vemurafenib — a BRAF inhibitor — after initial indication of its benefits.
The update of the multicenter study — reported by Axel Hauschild, MD, professor of dermatology at University Hospital in Kiel, Germany, and colleagues — included 675 patients with untreated, unresectable stage IIIC or IV melanoma who harbored the BRAFV600 mutation. Patients received 960 mg oral vemurafenib twice daily or 1,000 mg/m2 IV dacarbazine every 3 weeks.
Eighty-four patients crossed over to treatment with vemurafenib.
Median follow-up was 13.4 months (range, 0.4-33.3) for the vemurafenib arm and 9.2 months (range, 0-32.5) for the dacarbazine arm.
Median OS was 13.6 months (95% CI, 12-15.3) among patients who received vemurafenib and 9.7 months (95% CI, 7.9-12.8) among patients who received dacarbazine.
OS at 12 months was 56% in the vemurafenib arm and 44% for the dacarbazine arm. OS at 18 months was 40% in the vemurafenib arm and 35% in the dacarbazine arm.
After censoring for patients who crossed over, researchers calculated a 0.78 HR (95% CI, 0.64-0.94) for death in favor of vemurafenib. Without censoring for patients who crossed over, the HR was 0.79 (95% CI, 0.66-0.95).
More patients who received dacarbazine received anticancer therapy after study treatment (48% vs. 43%). Among these patients, 24% of those in the dacarbazine arm and 22% in the vemurafenib arm received ipilimumab (Yervoy, Bristol-Myers Squibb).
Researchers reported higher rates of arthralgia (56% vs. 4%), fatigue (47% vs. 35%), rash (41% vs. 2%) and photosensitivity (40% vs. 5%) in the vemurafenib arm. Nausea was more common in the dacarbazine arm (45% vs. 38%).
Twenty-four patients (7%) treated with vemurafenib discontinued treatment or withdrew from the study due to adverse events, compared with seven patients (2%) in the dacarbazine arm.
“In this updated OS analysis ... of BRIM-3, vemurafenib continues to be associated with clinically meaningful improvement in OS,” Hauschild and colleagues wrote.
For more information:
Hauschild A. Vemurafenib improves OS compared with dacarbazine in advanced BRAF V600-mutated melanoma: Updated results from a phase 3 randomized, multicenter trial. Presented at: Society for Melanoma Research 2013 Congress; Nov. 17-20, 2013; Philadelphia.
Disclosure: Two of the researchers report employment with Genentech.