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J Clin Oncol. 2018 Mar 1;36(7):667-673. doi: 10.1200/JCO.2017.74.1025. Epub 2017 Oct 9.

Long-Term Outcomes in Patients With BRAF V600-Mutant Metastatic Melanoma Who Received Dabrafenib Combined With Trametinib.

Author information

1
Georgina V. Long, University of Sydney, and Royal North Shore Hospital; Richard Kefford, Macquarie University, Sydney, and Westmead Hospital, Westmead, New South Wales; Jonathan Cebon, Ludwig Institute for Cancer Research, Melbourne, Victoria, Australia; Zeynep Eroglu, Moffitt Cancer Center, Tampa, FL; Jeffrey Infante, Tennessee Oncology; Douglas B. Johnson, Vanderbilt-Ingram Cancer Center, Nashville, TN; Sapna Patel, The University of Texas MD Anderson Cancer Center, Houston, TX; Adil Daud, University of California, San Francisco, San Francisco; Omid Hamid, The Angeles Clinic and Research Institute, Los Angeles, CA; Rene Gonzalez, University of Colorado, Denver, CO; Lynn Schuchter, University of Pennsylvania, Philadelphia, PA; William Sharfman, Sidney Kimmel Cancer Center, Baltimore, MD; Robert McWilliams, Mayo Clinic, Rochester, MN; Mario Sznol, Yale University, New Haven, CT; Suman Redhu, Eduard Gasal, and Bijoyesh Mookerjee, Novartis, East Hanover, NJ; Jeffrey Weber, New York University Langone Medical Center, New York, NY; and Keith T. Flaherty, Dana-Farber/Harvard Cancer Center, Boston, MA.

Abstract

Purpose To report 5-year landmark analysis efficacy and safety outcomes in patients with BRAF V600-mutant metastatic melanoma (MM) who received BRAF inhibitor dabrafenib (D) and MEK inhibitor trametinib (T) combination therapy versus D monotherapy in the randomized phase II BRF113220 study part C. Patients and Methods BRAF inhibitor-naive patients with BRAF V600-mutant MM were randomly assigned 1:1:1 to receive D 150 mg twice a day, D 150 mg twice a day plus T 1 mg once daily, or D 150 mg twice a day plus T 2 mg once daily (D + T 150/2). Patients who received D monotherapy could cross over to D + T 150/2 postprogression. Efficacy and safety were analyzed 4 and 5 years after initiation in patients with ≥ 5 years of follow-up. Results As of October 13, 2016, 18 patients who received D + T 150/2 remained in the study (13 [24%] of 54 enrolled at this dose plus five [11%] of 45 initially administered D who crossed over to D + T). With D + T 150/2, overall survival (OS; 4 years, 30%; 5 years, 28%) and progression-free survival (4 and 5 years, both 13%) appeared to stabilize with extended follow-up. Increased OS was observed in patients who received D + T with baseline normal lactate dehydrogenase (5 years, 45%) and normal lactate dehydrogenase with fewer than three organ sites with metastasis (5 years, 51%). With extended follow-up, one additional patient who received D + T 150/2 improved from a partial to a complete response. No new safety signals were observed. Conclusion This 5-year analysis represents the longest follow-up to date with BRAF + MEK inhibitor combination therapy in BRAF V600-mutant MM. Consistent with trends observed in landmark analyses with shorter follow-up, this therapy elicits durable plateaus of long-term OS and progression-free survival that last ≥ 5 years in some patients with MM.

TRIAL REGISTRATION:

ClinicalTrials.gov NCT01072175.

PMID:
28991513
DOI:
10.1200/JCO.2017.74.1025

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