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
COMBI-MB: A phase II study of combination dabrafenib (D) and trametinib (T) in patients (pts) with BRAF V600–mutant (mut) melanoma brain metastases (MBM).
2017 ASCO Annual Meeting
J Clin Oncol 35, 2017 (suppl; abstr 9506)
Author(s): Michael A. Davies, Caroline Robert, Georgina V. Long, Jean Jacques Grob, Keith T. Flaherty, Ana Arance, Vanna Chiarion-Sileni, Luc Thomas, Thierry Lesimple, Laurent Mortier, Stergios J. Moschos, David Hogg, Ivan Marquez Rodas, Michele Del Vecchio, Celeste Lebbe, Nicolas Meyer, Ying Zhang, Yingjie Huang, Bijoyesh Mookerjee, Philippe Saiag; The University of Texas MD Anderson Cancer Center, Houston, TX; Gustave Roussy Comprehensive Cancer Center, Villejuif, France; Melanoma Institute of Australia and The University of Sydney, Sydney, Australia; Aix-Marseille University, Marseille, France; Dana-Farber Cancer Institute/Harvard Medical School and Massachusetts General Hospital, Boston, MA; Hospital Clínic de Barcelona, Barcelona, Spain; Veneto Oncology Research Institute, Padua, Italy; Centre Hospitalier Lyon-Sud, Lyon, France; Centre Eugène Marquis, Rennes, France; Centre Hospitalier Universitaire Lille, Lille, France; University of North Carolina Lineberger Comprehensive Cancer Center, Chapel Hill, NC; Princess Margaret Cancer Centre, Toronto, ON, Canada; Hospital General Universitario Gregorio Marañón, Madrid, Spain; Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy; University Paris Diderot, Paris, France; Institut Universitaire du Cancer - Oncopole, Toulouse, France; Novartis Pharmaceuticals Corporation, East Hanover, NJ; Université Versailles Saint-Quentin-en-Yvelines, Versailles, France
Background: CNS metastases are common and associated with very poor prognosis in pts with metastatic melanoma (MM). In the phase II BREAK-MB trial, D had clinical activity in BRAF V600–mut MBM. D + T has shown superiority over D alone in pts with BRAF V600–mut mm without MBM; however, efficacy of this regimen on MBM has not been characterized. Here, we report results from a phase II trial of D + T in BRAFV600–mut MBM (COMBI-MB; NCT02039947). Methods: This open-label, phase II study evaluated D 150 mg BID + T 2 mg QD in 4 MBM cohorts: (A) BRAFV600E, asymptomatic MBM, no prior local treatment (Tx); (B) BRAFV600E, asymptomatic MBM, prior local Tx; (C) BRAFV600D/K/R, asymptomatic MBM, with or without prior local Tx; and (D) BRAFV600D/E/K/R, symptomatic MBM, with or without prior local Tx. The primary objective was intracranial response rate (IRR) in cohort A (null hypothesis, IRR ≤ 35%). Secondary endpoints included IRR in cohorts B, C, and D; extracranial (ERR) and overall (ORR) response rates; intracranial (IDCR), extracranial (EDCR), and overall (ODCR) disease control rates; duration of IR, ER, and OR; PFS; OS; and safety. Results: 125 pts were enrolled (A, n = 76; B, n = 16; C, n = 16; D, n = 17). In cohort A, median age was 52, 53% were male, and 37% had LDH > ULN. At data cutoff (28 Nov 2016; median f/u, 9.0 mo), in cohort A, investigator-assessed IRR was 58% (IDCR, 78%), ERR was 55% (EDCR, 80%), and ORR was 58% (ODCR, 80%). Median duration of IR, ER, and OR was 6.5 mo (95% CI, 4.9-10.3), 10.2 mo (95% CI, 6.5-13.0), and 6.5 mo (95% CI, 4.9-10.3), respectively. Median PFS was 5.6 mo (95% CI, 5.3-7.4). Independent review supported these results. 6-mo OS was 79%; with 31 pts (41%) still in f/u, preliminary median OS was 10.8 mo (95% CI, 8.7-19.6). Efficacy in cohorts B, C, and D will be reported. AEs across cohorts (any, 98%; grade 3/4, 48%) were consistent with prior D + T studies; 10% of pts (8% in cohort A) discontinued due to AEs. Conclusions: In this first report of a phase II trial evaluating a BRAF and MEK inhibitor combination in BRAFV600–mut MBM, the primary endpoint was met. Promising IRR and IDCR were seen with D + T, but responses appear less durable than reported for mm without MBMs. No unexpected safety issues were observed. Clinical trial information: NCT02039947
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