Vemurafenib in patients with BRAFV600 mutation-positive metastatic melanoma: final overall survival results of the randomized BRIM-3 study

被引：195

作者：

Chapman, P. B. ^{[1
]}

Robert, C. ^{[2
,3
]}

Larkin, J. ^{[4
]}

Haanen, J. B. ^{[5
]}

Ribas, A. ^{[6
]}

Hogg, D. ^{[7
,8
]}

Hamid, O. ^{[9
]}

Ascierto, P. A. ^{[10
]}

Testori, A. ^{[11
]}

Lorigan, P. C. ^{[12
]}

Dummer, R. ^{[13
]}

Sosman, J. A. ^{[14
]}

Flaherty, K. T. ^{[15
]}

Chang, I. ^{[16
]}

Coleman, S. ^{[17
]}

Caro, I. ^{[18
]}

Hauschild, A. ^{[19
]}

McArthur, G. A. ^{[20
,21
]}

机构：

[1] Mem Sloan Kettering Canc Ctr, Dept Med, 1275 York Ave, New York, NY 10065 USA

[2] Inst Gustave Roussy, Dept Med, Paris, France

[3] Paris Sud Univ, Paris, France

[4] Royal Marsden NHS Fdn Trust, Dept Med, London, England

[5] Netherlands Canc Inst, Div Med Oncol, Amsterdam, Netherlands

[6] Univ Calif Los Angeles, Jonsson Comprehens Canc Ctr, Dept Med Hematol & Oncol, Los Angeles, CA 90024 USA

[7] Princess Margaret Hosp, Div Med Oncol & Hematol, Toronto, ON, Canada

[8] Univ Hlth Network, Toronto, ON, Canada

[9] Angeles Clin & Res Inst, Melanoma Therapeut, Los Angeles, CA USA

[10] Fdn G Pascale, Ist Nazl Tumori, Melanoma Canc Immunotherapy & Innovat Therapy Uni, Naples, Italy

[11] Ist Europeo Oncol, Melanoma & Sarcoma, Milan, Italy

[12] Univ Manchester, Dept Med Oncol, Manchester, Lancs, England

[13] Univ Zurich, Dept Dermatol, Zurich, Switzerland

[14] Northwestern Univ, Robert H Lurie Comprehens Canc Ctr, Dept Hematol Oncol, Chicago, IL 60611 USA

[15] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA

[16] Genentech Inc, Dept Biostat Prod Dev, Biometr, San Francisco, CA 94080 USA

[17] Genentech Inc, Clin Dept, San Francisco, CA 94080 USA

[18] Genentech Inc, Prod Dev, Oncol, San Francisco, CA 94080 USA

[19] Univ Hosp Schleswig Holstein, Dept Dermatol, Kiel, Germany

[20] Peter MacCallum Canc Ctr, Dept Oncol, East Melbourne, Australia

[21] Univ Melbourne, Dept Oncol, Parkville, Vic, Australia

来源：

ANNALS OF ONCOLOGY | 2017年 / 28卷 / 10期

关键词：

melanoma; BRAF mutation; vemurafenib; dacarbazine; OPEN-LABEL; UNTREATED MELANOMA; CONTROLLED-TRIAL; BRAF; PHASE-3; DABRAFENIB; TRAMETINIB; IPILIMUMAB; NIVOLUMAB; MULTICENTER;

D O I：

10.1093/annonc/mdx339

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Background: The BRIM-3 trial showed improved progression-free survival (PFS) and overall survival (OS) for vemurafenib compared with dacarbazine in treatment-naive patients with BRAF(V600) mutation-positive metastatic melanoma. We present final OS data from BRIM-3. Patients and methods: Patients were randomly assigned in a 1 : 1 ratio to receive vemurafenib (960 mg twice daily) or dacarbazine (1000 mg/m(2) every 3 weeks). OS and PFS were co-primary end points. OS was assessed in the intention-to-treat population, with and without censoring of data for dacarbazine patients who crossed over to vemurafenib. Results: Between 4 January 2010 and 16 December 2010, a total of 675 patients were randomized to vemurafenib (n = 337) or dacarbazine (n = 338, of whom 84 crossed over to vemurafenib). At the time of database lock (14 August 2015), median OS, censored at crossover, was significantly longer for vemurafenib than for dacarbazine {13.6 months [95% confidence interval (CI) 12.0-15.4] versus 9.7 months [95% CI 7.9-12.8; hazard ratio (HR) 0.81 [95% CI 0.67-0.98]; P = 0.03}, as was median OS without censoring at crossover [13.6 months (95% CI 12.0-15.4) versus 10.3 months (95% CI 9.1-12.8); HR 0.81 (95% CI 0.68-0.96); P = 0.01]. Kaplan-Meier estimates of OS rates for vemurafenib versus dacarbazine were 56% versus 46%, 30% versus 24%, 21% versus 19% and 17% versus 16% at 1, 2, 3 and 4 years, respectively. Overall, 173 of the 338 patients (51%) in the dacarbazine arm and 175 of the 337 (52%) of those in the vemurafenib arm received subsequent anticancer therapies, most commonly ipilimumab. Safety data were consistent with the primary analysis. Conclusions: Vemurafenib continues to be associated with improved median OS in the BRIM-3 trial after extended follow-up. OS curves converged after approximate to 3 years, likely as a result of crossover from dacarbazine to vemurafenib and receipt of subsequent anticancer therapies.

引用

页码：2581 / 2587

页数：7

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