Survival in BRAF V600–Mutant Advanced Melanoma Treated with Vemurafenib
| العنوان: | Survival in BRAF V600–Mutant Advanced Melanoma Treated with Vemurafenib |
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| المؤلفون: | Yu Shyr, Andrew K. Joe, Kevin B. Kim, Grant A. McArthur, Richard F. Kefford, Richard J. Lee, Antoni Ribas, Stergios J. Moschos, Thomas E. Hutson, Jiang Li, Jeffrey A. Sosman, Donald P. Lawrence, Ravi K. Amaravadi, H. Jeffrey Lawrence, Rene Gonzalez, Anna C. Pavlick, Karl D. Lewis, Jeffrey S. Weber, Lynn M. Schuchter, Fei Ye, Igor Puzanov, Peter Hersey, Keith T. Flaherty, Bartosz Chmielowski, K. B. Nolop |
| المصدر: | New England Journal of Medicine. 366:707-714 |
| بيانات النشر: | Massachusetts Medical Society, 2012. |
| سنة النشر: | 2012 |
| مصطلحات موضوعية: | Adult, Male, Proto-Oncogene Proteins B-raf, Oncology, Keratoacanthoma, medicine.medical_specialty, Indoles, Dacarbazine, Kaplan-Meier Estimate, Article, chemistry.chemical_compound, Internal medicine, medicine, Clinical endpoint, Humans, Neoplasm Metastasis, Vemurafenib, Melanoma, Aged, Cobimetinib, Sulfonamides, business.industry, Dabrafenib, General Medicine, Middle Aged, medicine.disease, Rash, Surgery, Treatment Outcome, chemistry, Mutation, Disease Progression, Female, medicine.symptom, business, medicine.drug |
| الوصف: | 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 vem urafenib 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; ClinicalTrials.gov number, NCT00949702.) |
| تدمد: | 1533-4406 0028-4793 |
| DOI: | 10.1056/nejmoa1112302 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::c50e9fb19e988db3f2994b7a39105541 https://doi.org/10.1056/nejmoa1112302 |
| Rights: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....c50e9fb19e988db3f2994b7a39105541 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 15334406 00284793 |
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| DOI: | 10.1056/nejmoa1112302 |