2017 ASCO Annual Meeting!
Session: Melanoma/Skin Cancers
Type: Oral Abstract Session
Time: Sunday June 4, 8:00 AM to 11:00 AM
Location: Arie Crown Theater
Five-year overall survival (OS) update from a phase II, open-label trial of dabrafenib (D) and trametinib (T) in patients (pts) with BRAF V600–mutant unresectable or metastatic melanoma (MM).
2017 ASCO Annual Meeting
J Clin Oncol 35, 2017 (suppl; abstr 9505)
Author(s): Georgina V. Long, Zeynep Eroglu, Jeffrey R. Infante, Sapna Pradyuman Patel, Adil Daud, Douglas Buckner Johnson, Rene Gonzalez, Richard Kefford, Omid Hamid, Lynn Mara Schuchter, Jonathan S. Cebon, William Howard Sharfman, Robert R. McWilliams, Mario Sznol, Jeffrey S. Weber, Bijoyesh Mookerjee, Eduard Gasal, Suman Redhu, Keith T. Flaherty; University of Sydney, Sydney, Australia; Moffitt Cancer Center, Tampa, FL; Tennessee Onc, Nashville, TN; The University of Texas MD Anderson Cancer Center, Houston, TX; University of California, San Francisco, San Francisco, CA; Vanderbilt University Ingram Cancer Center, Nashville, TN; University of Colorado, Denver, CO; Westmead Hospital and Macquarie University, Sydney, Australia; The Angeles Clinic and Research Institute, Los Angeles, CA; University of Pennsylvania, Philadelphia, PA; Ludwig Institute for Cancer Research, Melbourne, Australia; Johns Hopkins Kimmel Cancer Center, Baltimore, MD; Mayo Clinic, Rochester, MN; Yale University, New Haven, CT; NYU Langone Medical Center, New York, NY; Novartis Pharmaceuticals Corporation, East Hanover, NJ; Dana-Farber Cancer Institute/Harvard Cancer Center, Boston, MA
Background: D (BRAF inhibitor) + T (MEK inhibitor) combination therapy is associated with rapid clinical responses and has improved clinical outcomes in pts with BRAFV600–mutantMM, but long-term (˃ 3 y) clinical efficacy and safety data are limited. The longest follow-up to date of a randomized trial evaluating D+T at the approved dose (150 mg BID/2 mg QD [150/2]) was of the phase II study BRF113220 (part C; median, 45.6 mo) in which durable outcomes were achieved in some pts with BRAFV600–mutantMM (3-y OS, 38%). Here, we report updated 5-y landmark analyses to further characterize the impact of D+T in MM. Methods: Pts with BRAFV600–mutant mm enrolled in BRF113220 part C (NCT01072175) were randomized 1:1:1 to receive monotherapy D (150 mg BID), D+T (150 mg BID/1 mg QD), or D+T (150/2). Pts who progressed on D alone could cross over to the D+T 150/2 arm. Pt disposition, pt demographics, and 4- and 5-y efficacy and safety were analyzed for both the D-alone and D+T (approved 150/2 dose) arms. Results: This updated analysis represents an additional ≈ 2 y of follow-up (D and D+T arms; n = 54 each). As of 13 Oct 2016, 45 pts (83%) on D alone had crossed over to D+T. 20 pts were ongoing (D, n = 7 [13%]; D+T, n = 13 [24%]); 80% of D pts and 70% of D+T pts had died. D+T OS remained superior to D alone. The 4- and 5-y OS rates with D+T were 30% and 28%, respectively, demonstrating a stabilization of the OS curve. The PFS curve for D+T also remained stable (4- and 5-y: both 13%). Consistent with earlier results, the best OS for pts who received D+T was seen in pts with normal LDH (5-y, 45%) and normal LDH with disease in < 3 organ sites (5-y, 51%). At the 5-y landmark, 1 additional pt who received D+T improved from a partial to a complete response. Additional follow-up revealed no new safety signals with D+T. Detailed analyses of D crossover pts, responders, and post-progression therapy will be presented. Conclusions: This longest follow-up to date of BRAF + MEK inhibitor combination therapy in pts with BRAFV600–mutant mm revealed stable OS and PFS lasting ≥ 5 y with consistent tolerability. These results demonstrate that some pts with mm can achieve durable benefit with D+T therapy. Clinical trial information: NCT01072175
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