Hallmeyer Sigrun, Gonzalez Rene, Lawson David H, Cranmer Lee D, Linette Gerald P, Puzanov Igor, Taback Bret, Cowey C Lance, Ribas Antoni, Daniels Gregory A, Moore Timothy, Gibney Geoffrey T, Tawbi Hussein, Whitman Eric, Lee Geraldine, Mun Yong, Liu Shiyao, Hamid Omid
aDepartment of Internal Medicine, Advocate Medical Group - Oncology North, Park Ridge, Illinois bMelanoma Research Clinic, University of Colorado Cancer Center, Aurora, Colorado cDepartment of Hematology and Medical Oncology, Winship Cancer Institute of Emory University, Atlanta, Georgia dDepartment of Hematology and Oncology, The University of Arizona Cancer Center, Tucson, Arizona eDepartment of Medicine, Washington University School of Medicine, St Louis, Missouri fDepartment of Hematology-Oncology, Vanderbilt University Medical Center, Nashville, Tennessee gDepartment of Surgery, Columbia University Medical Center, New York, New York hDepartment of Medical Oncology, Texas Oncology, Dallas, Texas iDepartment of Medicine, Jonsson Comprehensive Cancer Center at University of California jDepartment of Immuno-Oncology, The Angeles Clinic and Research Institute, Los Angeles kDepartment of Oncology, Moores Cancer Center, University of California, San Diego, La Jolla lGenentech Inc., South San Francisco, California mMid Ohio Oncology and Hematology Inc., Columbus, Ohio nDepartment of Melanoma, Georgetown-Lombardi Comprehensive Cancer Center, Washington, DC oDepartment of Pathology, University of Pittsburgh Cancer Institute and University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania pDepartment of Melanoma, Carol G. Simon Cancer Center, Atlantic Health System, Morristown, New Jersey, USA.
Melanoma Res. 2017 Dec;27(6):585-590. doi: 10.1097/CMR.0000000000000398.
BRAF mutations are found in ~50% of metastatic melanomas, most commonly in codon V600. Vemurafenib improves progression-free survival and overall survival in patients with advanced BRAF-mutated melanoma. The results of a descriptive study evaluating vemurafenib in patients with advanced melanoma harbouring BRAF mutations other than V600E are reported. Eligible patients with stage IIIC or IV melanoma and non-V600E BRAF mutations received vemurafenib (960 mg, twice daily). End points included investigator-assessed best overall response rate (primary), time to response, duration of response, progression-free survival, overall survival and safety. Planned (V600K vs. non-V600K mutations) subgroup analyses were carried out. Thirty-one patients were enrolled; 13 (42%) had V600K mutations and 18 (58%) had other mutations. Investigator-assessed confirmed that the best overall response rate was 23% (95% confidence interval=10-41%) in the overall population, and was similar between patients with V600K mutations (23%; 95% confidence interval=5-54%) versus other mutations (22%; 95% confidence interval=6-48%). Responses were observed in patients with V600K (n=3), V600E2 (n=1), V600R (n=1), L597S (n=1) and D594G (n=1) mutations. No new safety signals were reported. Vemurafenib showed activity in patients with advanced melanoma with rarer BRAF mutations.
约50%的转移性黑色素瘤中存在BRAF突变，最常见于密码子V600。维莫非尼可改善晚期BRAF突变型黑色素瘤患者的无进展生存期和总生存期。本文报告了一项描述性研究的结果，该研究评估了维莫非尼在携带非V600E BRAF突变的晚期黑色素瘤患者中的疗效。符合条件的IIIC期或IV期黑色素瘤且有非V600E BRAF突变的患者接受维莫非尼治疗（960毫克，每日两次）。终点指标包括研究者评估的最佳总体缓解率（主要指标）、缓解时间、缓解持续时间、无进展生存期、总生存期和安全性。进行了计划中的亚组分析（V600K与非V600K突变）。共纳入31例患者；13例（42%）有V600K突变，18例（58%）有其他突变。研究者评估确认，总体人群的最佳总体缓解率为23%（95%置信区间=10-41%），V600K突变患者（23%；95%置信区间=5-54%）与其他突变患者（22%；95%置信区间=6-48%）的缓解率相似。在有V600K（n=3）、V600E2（n=1）、V600R（n=1）、L597S（n=1）和D594G（n=1）突变的患者中观察到缓解。未报告新的安全信号。维莫非尼在携带罕见BRAF突变的晚期黑色素瘤患者中显示出活性。
