- Title
- Survival in BRAF V600-mutant advanced melanoma treated with vemurafenib
- Creator
- Sosman, Jeffery A.; Kim, Kevin B.; Hersey, Peter; Kefford, Richard; Lawrence, Donald; Puzanov, Igor; Lewis, Karl D.; Amaravadi, Ravi K.; Chmielowski, Bartosz; Lawrence, H. Jeffrey; Shyr, Yu; Ye, Fei; Schuchter, Lynn; Gonzalez, Rene; Pavlick, Anna C.; Weber, Jeffrey S.; McArthur, Grant A.; Hutson, Thomas E.; Moschos, Stergios J.; Flaherty, Keith T.
- Relation
- New England Journal of Medicine Vol. 366, Issue 8, p. 707-714
- Publisher Link
- http://dx.doi.org/10.1056/NEJMoa1112302
- Publisher
- Massachusetts Medical Society
- Resource Type
- journal article
- Date
- 2012
- Description
- Background: Approximately 50% of melanomas harbor activating (V600) mutations in the serinethreonine protein kinase B-RAF (BRAF). The oral BRAF inhibitor vemurafenib (PLX4032) frequently produced tumor regressions in patients with BRAF V600-mutant metastatic melanoma in a phase 1 trial and improved overall survival in a phase 3 trial. Methods: We designed a multicenter phase 2 trial of vemurafenib in patients with previously treated BRAF V600-mutant metastatic melanoma to investigate the efficacy of vemurafenib with respect to overall response rate (percentage of treated patients with a tumor response), duration of response, and overall survival. The primary end point was the overall response rate as ascertained by the independent review committee; overall survival was a secondary end point. Results: A total of 132 patients had a median follow-up of 12.9 months (range, 0.6 to 20.1). The confirmed overall response rate was 53% (95% confidence interval [CI], 44 to 62; 6% with a complete response and 47% with a partial response), the median duration of response was 6.7 months (95% CI, 5.6 to 8.6), and the median progression-free survival was 6.8 months (95% CI, 5.6 to 8.1). Primary progression was observed in only 14% of patients. Some patients had a response after receiving vemurafenib for more than 6 months. The median overall survival was 15.9 months (95% CI, 11.6 to 18.3). The most common adverse events were grade 1 or 2 arthralgia, rash, photosensitivity, fatigue, and alopecia. Cutaneous squamous-cell carcinomas (the majority, keratoacanthoma type) were diagnosed in 26% of patients. Conclusions: Vemurafenib induces clinical responses in more than half of patients with previously treated BRAF V600-mutant metastatic melanoma. In this study with a long follow-up, the median overall survival was approximately 16 months.
- Subject
- melanoma; vemurafenib; medical trial
- Identifier
- http://hdl.handle.net/1959.13/1340666
- Identifier
- uon:28543
- Identifier
- ISSN:0028-4793
- Rights
- From New England Journal of Medicine, Jeffrey A. Sosman et al., Survival in BRAF V600–Mutant Advanced Melanoma Treated with Vemurafenib, volume no.366, Page No.707-714 Copyright © (2012) Massachusetts Medical Society. Reprinted with permission.
- Language
- eng
- Full Text
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