Survival in BRAF V600-mutant advanced melanoma treated with vemurafenib

Jeffrey A. Sosman*, Kevin B. Kim, Lynn Schuchter, Rene Gonzalez, Anna C. Pavlick, Jeffrey S. Weber, Grant A. McArthur, Thomas E. Hutson, Stergios J. Moschos, Keith T. Flaherty, Peter Hersey, Richard Kefford, Donald Lawrence, Igor Puzanov, Karl D. Lewis, Ravi K. Amaravadi, Bartosz Chmielowski, H. Jeffrey Lawrence, Yu Shyr, Fei YeJiang Li, Keith B. Nolop, Richard J. Lee, Andrew K. Joe, Antoni Ribas

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

1797 Citations (Scopus)


BACKGROUND: Approximately 50% of melanomas harbor activating (V600) mutations in the serine-threonine 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. (Funded by Hoffmann-La Roche; number, NCT00949702.)

Original languageEnglish
Pages (from-to)707-714
Number of pages8
JournalNew England Journal of Medicine
Issue number8
Publication statusPublished - 23 Feb 2012
Externally publishedYes


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