Medline ® Abstract for Reference 39
of 'Molecularly targeted therapy for metastatic melanoma'
Long-Term Outcomes in Patients With BRAF V600-Mutant Metastatic Melanoma Who Received Dabrafenib Combined With Trametinib.
Long GV, Eroglu Z, Infante J, Patel S, Daud A, Johnson DB, Gonzalez R, Kefford R, Hamid O, Schuchter L, Cebon J, Sharfman W, McWilliams R, Sznol M, Redhu S, Gasal E, Mookerjee B, Weber J, Flaherty KT
J Clin Oncol. 2017;
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 patientswith 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.
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 Unive