LBA6__PR - COMBI-AD: Adjuvant dabrafenib (D) plus trametinib (T) for resected stage III BRAF V600E/K–mutant melanoma

Date 11 September 2017
Event ESMO 2017 Congress
Session Presidential Symposium III
Topics Anti-Cancer Agents & Biologic Therapy
Melanoma and other Skin Tumours
Presenter Axel Hauschild
Citation Annals of Oncology (2017) 28 (suppl_5): v605-v649. 10.1093/annonc/mdx440
Authors A. Hauschild1, M. Santinami2, G.V. Long3, V. Atkinson4, M. Mandala5, V. Chiarion Sileni6, M.S. Nyakas7, C. Dutriaux8, A. Haydon9, C. Robert10, L. Mortier11, J. Schachter12, R. Ji13, P. Zhang13, B. Mookerjee13, J. Legos13, R. Kefford14, R. Dummer15, J. Kirkwood16
  • 1Dermatology, University Hospital Schleswig-Holstein, 24105 - Kiel/DE
  • 2Oncology, Fondazione Istituto Nazionale Tumori, Milan/IT
  • 3Melanoma Medical Oncology, Melanoma Institute Australia, The University of Sydney, Royal North Shore and Mater Hospitals, Sydney/AU
  • 4Medical Oncology, Princess Alexandra Hospital, Gallipoli Medical Research Foundation, University of Queensland, Queensland/AU
  • 5Department Of Oncology And Haematology, Papa Giovanni XXIII Cancer Center Hospital, Bergamo/IT
  • 6Melanoma Oncology Unit, Veneto Oncology Institute, Padova/IT
  • 7Department Of Oncology, Rikshospitalet-Radiumhospitalet HF, Oslo/NO
  • 8Department Of Oncologic Dermatology, Centre Hospitalier Universitaire de Bordeaux, Hôpital Saint-André, Bordeaux/FR
  • 9Medical Oncology, The Alfred Hospital, Melbourne/AU
  • 10Dermatology, Institute Gustave Roussy, Paris/FR
  • 11Dermatology, Université de Lille, Lille/FR
  • 12Oncology, Ella Institute for Melanoma, Sheba Medical Center, Tel Hashomer/IL
  • 13Medical Oncology, Novartis Pharmaceuticals Corporation, East Hanover/US
  • 14Medical Oncology, Macquarie University, Melanoma Institute Australia, Westmead Hospital, and the University of Sydney, Sydney/AU
  • 15Dermatology, University Hospital Zürich Skin Cancer Center, Zürich/CH
  • 16Melanoma Program, Hillman UPMC Cancer Center, University of Pittsburgh, Pittsburgh/US

Abstract

Background

Surgery is curative for most patients (pts) with localized melanoma; however, those with regional nodal involvement (stage III disease) are at a higher risk for relapse and death after resection. In phase 3 trials of advanced or metastatic BRAF V600–mutant melanoma, D+T combination therapy improved clinical outcomes and was well tolerated.

Methods

In this randomized, double-blind, placebo-controlled, phase 3 study (COMBI-AD [NCT01682083]), pts with high-risk, stage III, BRAF V600E/K–mutant melanoma without prior anticancer therapy were randomized 1:1 within 12 weeks of complete surgical resection to receive D 150 mg twice daily plus T 2 mg once daily or matching placebos. Pts were treated for 12 months and stratified based on BRAFmutation (V600E vs V600K) and stage (IIIA vs IIIB vs IIIC). The primary endpoint was relapse-free survival (RFS). Secondary endpoints included overall survival (OS), distant metastasis-free survival (DMFS), freedom from relapse (FFR), and safety.

Results

A total of 870 pts (stage IIIA, 18%; IIIB, 41%; IIIC, 40%; unknown, 1%) were randomized (D+T, n = 438; placebo, n = 432). The primary endpoint was met. At the time of the data cutoff for the primary analysis (June 30, 2017; median follow-up, 2.8 years), D+T significantly reduced the risk of disease recurrence or death by 53% vs placebo (HR, 0.47 [95% CI, 0.39-0.58]; median not reached vs 16.6 months, respectively; P

Conclusions

Combination D+T adjuvant therapy was associated with improvements in RFS, OS, DMFS, and FFR, and manageable safety in pts with high-risk, resected, stage III, BRAF V600E/K–mutant melanoma. This regimen represents a new adjuvant treatment option in this setting.

Clinical trial identification

ClinicalTrials.gov number: NCT01682083, EudraCT number: 2012-001266-15 Release date: May 31, 2017

Legal entity responsible for the study

GlaxoSmithKline

Funding

GlaxoSmithKline

Disclosure

A. Hauschild: Clinical trial support or speakeŕs honoraria or consultancy fees from Amgen, BMS, MerckSerono, MSD, Novartis, OncoSec, Philogen, Pierre Fabre, Provectus, Regeneron, Roche during the conduct of the study. G.V. Long: Personal fees as a consultant advisor to BMS, Novartis, Roche, Amgen, Merck MSD, Pierre Fabre, and Array outside the submitted work. V. Atkinson: Travel reimbursement and advisory board speaker\'s fees from MSD, BMS, and Novartis, speaker\'s fees from Roche, and advisory board fees from Pierre Fabre outside the submitted work. M. Mandala: Advisory board, lectures, and research activity fees from Roche; and advisory board and lecture fees from Novartis, MSD, and BMS outside the submitted work. V. Chiarion Sileni: Assistance with manuscript preparation from ArticulateScience, LLC, and advisory board fees from BMS, MSD, Roche, Novartis, and Merck Serono during the conduct of the study. M.S. Nyakas, C. Dutriaux: Assistance with manuscript preparation from ArticulateScience, LLC, during the conduct of this study. A. Haydon: Lecture fees from Novartis during the conduct of the study. C. Robert: Advisory board fees from BMS, MSD, Novartis, and Roche during the conduct of the study. L. Mortier: Assistance with manuscript preparation from ArticulateScience, LLC, and medical board fees from Novartis during the conduct of this study; and medical board fees from Roche outside the submitted work. R. Ji, P. Zhang: Employment by Novartis during the conduct of the study. B. Mookerjee: Employment and stock options from Novartis and stock options from GlaxoSmithKline during the conduct of the study; employment and stock options from Novartis and GlaxoSmithKline outside the submitted work. J. Legos: Employment by and shareholder of Novartis and non-financial support from ArticulateScience, LLC, during the conduct of the study. R. Kefford: Institutional reimbursement advisory boards fees from Novartis during the conduct of the study and institutional reimbursement advisory boards fees from BMS, Merck, Amgen, and Teva outside the submitted work. R. Dummer: Intermittent, project-focused consulting and/or advisory relationships with Novartis, MSD, BMS, Roche, Amgen, Takeda, and Pierre Fabre outside the submitted work. J. Kirkwood: Grants from Merck and Prometheus and personal fees from Prometheus, BMS, Novartis, Roche, Genentech, EMD Serono, and ArrAY Biopharma outside the submitted work. All other authors have declared no conflicts of interest.