Medline ® Abstract for Reference 44
Overall Survival and Durable Responses in Patients With BRAF V600-Mutant Metastatic Melanoma Receiving Dabrafenib Combined With Trametinib.
Long GV, Weber JS, Infante JR, Kim KB, Daud A, Gonzalez R, Sosman JA, Hamid O, Schuchter L, Cebon J, Kefford RF, Lawrence D, Kudchadkar R, Burris HA 3rd, Falchook GS, Algazi A, Lewis K, Puzanov I, Ibrahim N, Sun P, Cunningham E, Kline AS, Del Buono H, McDowell DO, Patel K, Flaherty KT
J Clin Oncol. 2016;34(8):871.
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.
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. firstname.lastname@example.org.