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Poster display session: Basic science, Endocrine tumours, Gastrointestinal tumours - colorectal & non-colorectal, Head and neck cancer (excluding thyroid), Melanoma and other skin tumours, Neuroendocrine tumours, Thyroid cancer, Tumour biology & pathology

3817 - Estimate of long-term relapse-free survival (RFS) and analysis of baseline factors associated with RFS in the COMBI-AD trial


21 Oct 2018


Poster display session: Basic science, Endocrine tumours, Gastrointestinal tumours - colorectal & non-colorectal, Head and neck cancer (excluding thyroid), Melanoma and other skin tumours, Neuroendocrine tumours, Thyroid cancer, Tumour biology & pathology


Tumour Site



Reinhard Dummer


Annals of Oncology (2018) 29 (suppl_8): viii442-viii466. 10.1093/annonc/mdy289


R. Dummer1, D. Schadendorf2, A. Hauschild3, M. Santinami4, V.G. Atkinson5, M. Mandala6, V. Chiarion Sileni7, J. Larkin8, M.S. Nyakas9, C. Dutriaux10, A. Haydon11, L. Mortier12, C. Robert13, J. Schachter14, X. Feng15, E. de Jong16, B. Mookerjee15, R. Kefford17, J.M. Kirkwood18, G.V. Long19

Author affiliations

  • 1 Department Of Dermatology, University Hospital Zürich Skin Cancer Center, 8091 - Zürich/CH
  • 2 Department Of Dermatology, University Hospital Essen, 45122 - Essen/DE
  • 3 Department Of Dermatology, University Hospital Schleswig-Holstein, 24105 - Kiel/DE
  • 4 Melanomi E Sarcomi, Fondazione Istituto Nazionale Tumori, Milano/IT
  • 5 Division Of Cancer Services, Princess Alexandra Hospital, Gallipoli Medical Research Foundation, University of Queensland, 4102 - Queensland/AU
  • 6 Division Of Oncology, Papa Giovanni XXIII Cancer Center Hospital, Bergamo/IT
  • 7 Melanoma Oncology Unit, Veneto Oncology Institute, Padova/IT
  • 8 Department Of Medical Oncology, Royal Marsden NHS Foundation Trust, London/GB
  • 9 Department Of Oncology, Oslo University Hospital, The Norwegian Radium Hospital, Oslo/NO
  • 10 Service De Dermatologie Et Dermatologie Pédiatrique, Centre Hospitalier Universitaire de Bordeaux, Hôpital Saint-André, Bordeaux/FR
  • 11 Department Of Medical Oncology, The Alfred Hospital, Melbourne/AU
  • 12 Service De Dermatologie, Université de Lille, INSERM U 1189, Lille/FR
  • 13 Department Of Medicine, Institute Gustave Roussy, 94800 - Paris/FR
  • 14 Division Of Oncology, Ella Institute for Melanoma, Sheba Medical Center, Tel Hashomer/IL
  • 15 Global Clinical Program, Novartis Pharmaceuticals Corporation, East Hanover/US
  • 16 Global Medical Affairs Oncology, Novartis Pharmaceuticals Corporation, East Hanover/US
  • 17 Department Of Medical Oncology, Macquarie University, Melanoma Institute Australia, Westmead Hospital, and The University of Sydney, Sydney/AU
  • 18 Melanoma Program, Upmc Hillman Cancer Center, & Department Of Medicine, University of Pittsburgh, Pittsburgh/US
  • 19 Department Of Medical Oncology, Melanoma Institute Australia, The University of Sydney, Royal North Shore and Mater Hospitals, 2060 - North Sydney/AU

Abstract 3817


Adjuvant therapy with dabrafenib plus trametinib (D + T) for 12 months significantly reduced the risk of relapse or death vs placebo (Pbo; HR, 0.47; P < .001) in patients (pts) in the COMBI-AD trial with resected BRAF V600–mutant stage III melanoma (NCT01682083), leading to the recent US FDA approval in this indication. We used a cure-rate model to estimate long-term RFS benefit and explore the association of baseline factors with RFS to better characterize pts likely to benefit from adjuvant treatment.


COMBI-AD randomized pts with completely resected BRAF V600E/K–mutant stage III melanoma to receive adjuvant D (150 mg twice daily) + T (2 mg once daily) or Pbo for 12 months. Long-term RFS (proportion of pts who did not experience an event) was estimated using a Weibull cure-rate model. Baseline covariates were analyzed using a stratified Cox regression model for RFS, with P values calculated using a Wald χ2 test. AJCC 7th edition criteria were used for pt staging at baseline.


Eight hundred seventy pts were enrolled (D + T, n = 438; Pbo, n = 432). The median follow-up was 2.8 years. Estimation of long-term RFS using a cure-rate model showed a 55% (95% CI, 49%-61%) long-term RFS rate in the D + T arm vs 38% (95% CI, 33%-43%) in the Pbo arm. Evaluation of the association between baseline disease characteristics and RFS demonstrated that lower T stage, lesser nodal involvement, and a superficial spreading melanoma subtype were independently associated with better RFS (Table). Conversely, tumor ulceration and the presence of in-transit metastases were not associated with RFS. With respect to baseline patient demographics, an association was observed between female sex and RFS benefit (P = .030). Table: 1250P

Stratified Cox regression model for RFS (N/na = 870/845)

CovariateEffect TestedHR (95% CI)P Value
SexMale/female1.25 (1.02-1.53).030
T stage1/4 2/4 3/40.49 (0.34-0.70) 0.76 (0.56-1.02) 0.89 (0.69-1.15)< .001 .071 .377
Tumor ulcerationYes/no0.94 (0.74-1.20).630
N stage1/3 2/30.67 (0.49-0.93) 0.78 (0.58-1.06).017 .109
In-transit metastasesYes/no1.05 (0.76-1.47).753
Melanoma subtypeSuperficial spreading/other Nodular/other0.73 (0.57-0.93) 0.88 (0.68-1.13).010 .321

N/n = total population/patients with data available for all covariates.


The results of the long-term RFS analysis suggest potential long-term RFS in > 50% of pts treated with D + T. Lower T stage and less nodal involvement at baseline were associated with better RFS.

Clinical trial identification


Legal entity responsible for the study

Novartis Pharmaceuticals Corporation.


Novartis Pharmaceuticals Corporation.

Editorial Acknowledgement

Medical writing assistance was provided by Michael Demars, PhD (ArticulateScience LLC), funded by Novartis Pharmaceuticals Corporation.


R. Dummer: Intermittent, consulting, advisor: Novartis, Merck Sharp & Dhome (MSD), Bristol-Myers Squibb, Roche, Amgen, Takeda, Pierre Fabre, Sun Pharma outside the submitted work. D. Schadendorf: Personal fees: Amgen, Boehringer Ingelheim, Leo Pharma, Roche, Novartis, Incyte, Regeneron, 4SC, AstraZeneca, Bristol-Myers Squibb, MS, Pierre Fabre, Merck-EMD, Pfizer, Philiogen, Array; Patients' fees to institution: MSD, Roche, Novartis, Regeneron, Brisol-Myers Squibb, Merck-EMD, Philiogen. A. Hauschild: Consultancy: Amgen, Bristol-Myers Squibb, Merck Serono, MSD/Merck, Novartis, Philogen, Pierre Fabre, Provectus, Regeneron, Roche, OncoSec; Research funding: Amgen, Bristol-Myers Squibb, Merck Serono, MSD/Merck, Novartis, Philogen, Pierre Fabre, Provectus, Regeneron, Roche; Honoraria: Amgen, Bristol-Myers Squibb, Merck Serono, MSD/Merck, Novartis, Philogen, Pierre Fabre, Provectus, Roche. V.G. Atkinson: Consulting or advisory role: Bristol-Myers Squibb, MSD, Novartis, Merck Serono, Pierre Fabre; Honoraria: Bristol-Myers Squibb, MSD, Novartis, Pierre Fabre, Merck Serono; Speakers’ bureau: Bristol-Myers Squibb, MSD, Novartis, Roche; Travel, accommodations, expenses: Bristol-Myers Squibb; . M. Mandala: Research funding, Honoraria, Speakers bureau: Novartis, Roche. V. Chiarion Sileni: Consultancy: Bristol-Myers Squibb, MSD, Novartis, Pierre-Fabre, Merck Serono. J. Larkin: Consultancy, Honoraria: Eisai, Bristol-Myers Squibb, MSD, GlaxoSmithKline, Kymab, Pfizer, Novartis, Roche, Genentech, Secarna, Pierre-Fabre, EUSA Pharma; Research funding: Bristol-Myers Squibb, MSD, Novartis, Pfizer. M.S. Nyakas: Honoraria (institution) for advisory board: Novartis, Incyte. C. Dutriaux: Consultancy: Bristol-Myers Squibb, MSD; Membership on board of directors or advisory committee: Bristol-Myers Squibb, Roche, Novartis, Merck Serono, MSD; Clinical trials investigator: Bristol-Myers Squibb, Roche, Novartis, Merck Serono, MSD, Amgen. A. Haydon: Honoraria: Novartis. L. Mortier: Research funding: Novartis. C. Robert: Advisory board participation: Merck, MSD, Novartis, Roche. J. Schachter: Honoraria: Bristol-Myers Squibb, MSD; Travel, accommodations, expenses: Bristol-Myers Squibb. X. Feng, E. de Jong: Employee: Novartis. B. Mookerjee: Employee: Novartis; Stock ownership: Novartis, GlaxoSmithKline, AstraZeneca. R. Kefford: Membership on board of directors or advisory committees: Bristol-Myers Squibb, Amgen, Merck, Novartis, Teva; Conference travel: Bristol-Myers Squibb, Amgen. J.M. Kirkwood: Consultancy: Bristol-Myers Squibb, Novartis, Array Biopharma, Merck, Roche, Amgen, Immunocore, Prometheus; Research funding: Merck. G.V. Long: Consultancy: Amgen, Bristol-Myers Squibb, Merck MSD, Novartis, Roche, Pierre-Fabre, Array; Honoraria: Bristol-Myers Squibb, MSD, Roche, Novartis, Incyte. All other authors have declared no conflicts of interest.

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