Journal article
Vemurafenib in patients with BRAFV600 mutation-positive metastatic melanoma: final overall survival results of the randomized BRIM-3 study.
- Chapman PB Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, USA. Electronic address: chapmanp@mskcc.org.
- Robert C Department of Medicine, Institut Gustave Roussy and Paris Sud University, Paris, France.
- Larkin J Department of Medicine, The Royal Marsden NHS Foundation Trust, London, UK.
- Haanen JB Division of Medical Oncology, The Netherlands Cancer Institute, Amsterdam, The Netherlands.
- Ribas A Department of Medicine, Hematology and Oncology, Jonsson Comprehensive Cancer Center at the University of California Los Angeles, Los Angeles, USA.
- Hogg D Division of Medical Oncology and Hematology, Princess Margaret Hospital and University Health Network, Toronto, Canada.
- Hamid O The Angeles Clinic and Research Institute, Melanoma Therapeutics, Los Angeles, USA.
- Ascierto PA Melanoma, Cancer Immunotherapy and Innovative Therapy Unit, Istituto Nazionale Tumori Fondazione G. Pascale, Naples.
- Testori A Melanoma and Sarcoma, Istituto Europeo di Oncologia, Milan, Italy.
- Lorigan PC Department of Medical Oncology, University of Manchester, Manchester, UK.
- Dummer R Department of Dermatology, University of Zurich, Zurich, Switzerland.
- Sosman JA Department of Hematology/Oncology, Robert H. Lurie Comprehensive Cancer Center of Northwestern University, Chicago, USA.
- Flaherty KT Department of Medicine, Massachusetts General Hospital, Boston, USA.
- Chang I Department of Biostatistics in Product Development, Biometrics, South San Francisco, USA.
- Coleman S Clinical Department, Oncology, Genentech Inc., South San Francisco, USA.
- Caro I Product Development, Oncology, Genentech Inc., South San Francisco, USA.
- Hauschild A Department of Dermatology, University Hospital Schleswig-Holstein, Kiel, Germany.
- McArthur GA Department of Oncology, Peter MacCallum Cancer Centre, East Melbourne, Australia; Department of Oncology, University of Melbourne, Parkville, Australia.
- 2017-09-30
Published in:
- Annals of oncology : official journal of the European Society for Medical Oncology. - 2017
BRAF mutation
dacarbazine
melanoma
vemurafenib
Adolescent
Adult
Aged
Aged, 80 and over
Antineoplastic Agents
Antineoplastic Agents, Alkylating
Dacarbazine
Enzyme Inhibitors
Female
Humans
Indoles
Kaplan-Meier Estimate
Male
Melanoma
Middle Aged
Mutation
Proto-Oncogene Proteins B-raf
Skin Neoplasms
Sulfonamides
Treatment Outcome
Vemurafenib
Young Adult
English
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 BRAFV600 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/m2 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 ≈3 years, likely as a result of crossover from dacarbazine to vemurafenib and receipt of subsequent anticancer therapies.
ClinicalTrials.gov
NCT01006980.
The BRIM-3 trial showed improved progression-free survival (PFS) and overall survival (OS) for vemurafenib compared with dacarbazine in treatment-naive patients with BRAFV600 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/m2 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 ≈3 years, likely as a result of crossover from dacarbazine to vemurafenib and receipt of subsequent anticancer therapies.
ClinicalTrials.gov
NCT01006980.
- Language
-
- English
- Open access status
- hybrid
- Identifiers
-
- DOI 10.1093/annonc/mdx339
- PMID 28961848
- Persistent URL
- https://folia.unifr.ch/global/documents/30122
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