In:
Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 29, No. 18_suppl ( 2011-06-20), p. LBA4-LBA4
Abstract:
LBA4 Background: About 50% of melanomas have an activating V600E BRAF mutation which led to the hypothesis that inhibition of the mutated BRAF kinase may be of clinical benefit. Phase I and II trials with vemurafenib (previously PLX4032/RO5185426), an orally available inhibitor of oncogenic BRAF kinase, showed response rates (RR; CR+PR) 〉 50% in V600E BRAF- mutated melanoma patients (pts). We conducted a phase III trial to determine if vemurafenib improved overall survival (OS) and progression-free survival (PFS) in melanoma pts with V600E BRAF mutation. Methods: Pts with previously untreated, unresectable stage IIIC or stage IV melanoma that tested positive for V600E BRAF mutation by the cobas 4800 BRAF V600 Mutation Test were randomized (1:1) to vemurafenib (960 mg po bid) or DTIC (1,000 mg/m 2 , IV, q3w). Randomization was stratified by PS, stage, LDH, and geographic region. Pts were assessed for tumor responses after weeks 6, 12, and then q9 weeks. Co-primary endpoints were OS and PFS on the intent-to-treat population; secondary endpoints included RR, response duration, and safety. Final analysis was planned at 196 deaths. Results: 675 pts were enrolled at 103 centers worldwide between Jan and Dec 2010. Treatment cohorts were well-balanced. At the pre-planned interim analysis (50% of deaths needed for final analysis), the hazard ratios for OS and PFS were 0.37 (95% CI 0.26 to 0.55; p 〈 0.0001) and 0.26 (95% CI 0.20 to 0.33; p 〈 0.0001), respectively, both in favor of vemurafenib. The confirmed RR was 48.4% and 5.5% to vemurafenib and DTIC, respectively, among the 65% of pts evaluable for RR to date. Benefit in OS, PFS, and RR was seen in all subgroups examined. Due to these data, the DTIC cohort has been allowed to cross over to vemurafenib. At the time of data analysis, 66% of vemurafenib pts and 25% DTIC pts were still on treatment. The most common toxicities of vemurafenib were: diarrhea, rash, alopecia, photosensitivity, fatigue, arthralgia, and keratoacanthoma/skin squamous cell carcinoma. Conclusions: Vemurafenib is associated with significantly improved OS and PFS compared to DTIC in pts with previously untreated, V600E BRAF-mutated metastatic melanoma.
Type of Medium:
Online Resource
ISSN:
0732-183X
,
1527-7755
DOI:
10.1200/jco.2011.29.18_suppl.lba4
Language:
English
Publisher:
American Society of Clinical Oncology (ASCO)
Publication Date:
2011
detail.hit.zdb_id:
2005181-5
