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J Clin Oncol. 2016 Mar 10;34(8):871-8. doi: 10.1200/JCO.2015.62.9345. Epub 2016 Jan 25.

Overall Survival and Durable Responses in Patients With BRAF V600-Mutant Metastatic Melanoma Receiving Dabrafenib Combined With Trametinib.

Author information

1
Georgina V. Long, Melanoma Institute Australia; The University of Sydney; Richard F. Kefford, Melanoma Institute Australia; The University of Sydney; Macquarie University, Sydney; Westmead Hospital, Westmead; Jonathan Cebon, Austin Health, Melbourne, Victoria, Australia; Jeffrey S. Weber and Ragini Kudchadkar, Moffitt Cancer Center, Tampa, FL; Jeffrey R. Infante and Howard A. Burris III, Sarah Cannon Research Institute/Tennessee Oncology; Kevin B. Kim, California Pacific Medical Center; Adil Daud, Alain Algazi, University of California, San Francisco, San Francisco; Omid Hamid, The Angeles Clinic and Research Institute, Los Angeles, CA; Rene Gonzalez, Karl Lewis, University of Colorado; Gerald S. Falchook, Sarah Cannon Research Institute at HealthONE, Denver, CO; Jeffrey A. Sosman, Igor Puzanov, Vanderbilt University Medical Center, Nashville, TN; Lynn Schuchter, University of Pennsylvania Abramson Cancer Center; Nageatte Ibrahim, Elizabeth Cunningham, Merck; Peng Sun, Amy S. Kline, Heather Del Buono, Diane Opatt McDowell, GlaxoSmithKline, Philadelphia, PA; Donald Lawrence and Kiran Patel, Incyte Corporation, Wilmington, DE; and Keith T. Flaherty, Massachusetts General Hospital Cancer Center, Boston, MA. georgina.long@sydney.edu.au.
2
Georgina V. Long, Melanoma Institute Australia; The University of Sydney; Richard F. Kefford, Melanoma Institute Australia; The University of Sydney; Macquarie University, Sydney; Westmead Hospital, Westmead; Jonathan Cebon, Austin Health, Melbourne, Victoria, Australia; Jeffrey S. Weber and Ragini Kudchadkar, Moffitt Cancer Center, Tampa, FL; Jeffrey R. Infante and Howard A. Burris III, Sarah Cannon Research Institute/Tennessee Oncology; Kevin B. Kim, California Pacific Medical Center; Adil Daud, Alain Algazi, University of California, San Francisco, San Francisco; Omid Hamid, The Angeles Clinic and Research Institute, Los Angeles, CA; Rene Gonzalez, Karl Lewis, University of Colorado; Gerald S. Falchook, Sarah Cannon Research Institute at HealthONE, Denver, CO; Jeffrey A. Sosman, Igor Puzanov, Vanderbilt University Medical Center, Nashville, TN; Lynn Schuchter, University of Pennsylvania Abramson Cancer Center; Nageatte Ibrahim, Elizabeth Cunningham, Merck; Peng Sun, Amy S. Kline, Heather Del Buono, Diane Opatt McDowell, GlaxoSmithKline, Philadelphia, PA; Donald Lawrence and Kiran Patel, Incyte Corporation, Wilmington, DE; and Keith T. Flaherty, Massachusetts General Hospital Cancer Center, Boston, MA.

Erratum in

Abstract

PURPOSE:

To report the overall survival (OS) and clinical characteristics of BRAF inhibitor-naive long-term responders and survivors treated with dabrafenib plus trametinib in a phase I and II study of patients with BRAF V600 mutation-positive metastatic melanoma.

METHODS:

BRAF inhibitor-naive patients treated with dabrafenib 150 mg twice daily plus trametinib 2 mg daily (the 150/2 group) from the non-randomly assigned (part B) and randomly assigned (part C) cohorts of the study were analyzed for progression-free and OS separately. Baseline characteristics and factors on treatment were analyzed for associations with durable responses and OS.

RESULTS:

For BRAF inhibitor-naive patients in the 150/2 groups (n = 78), the progression-free survival at 1, 2, and 3 years was 44%, 22%, and 18%, respectively, for part B (n = 24) and 41%, 25%, and 21%, respectively, for part C (n = 54). Median OS was 27.4 months in part B and 25 months in part C. OS at 1, 2, and 3 years was 72%, 60%, and 47%, respectively, for part B and 80%, 51%, and 38%, respectively, for part C. Prolonged survival was associated with metastases in fewer than three organ sites and lower baseline lactate dehydrogenase. OS at 3 years was 62% in patients with normal baseline lactate dehydrogenase and 63% in patients with a complete response.

CONCLUSION:

Dabrafenib plus trametinib results in a median OS of more than 2 years in BRAF inhibitor-naive patients with BRAF V600 mutation-positive metastatic melanoma, and approximately 20% were progression free at 3 years. Durable responses occurred in patients with good prognostic features at baseline, which may be predictive.

TRIAL REGISTRATION:

ClinicalTrials.gov NCT01072175.

PMID:
26811525
DOI:
10.1200/JCO.2015.62.9345
[Indexed for MEDLINE]

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