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J Clin Oncol. 2018 Oct 22:JCO1801219. doi: 10.1200/JCO.18.01219. [Epub ahead of print]

Longer Follow-Up Confirms Relapse-Free Survival Benefit With Adjuvant Dabrafenib Plus Trametinib in Patients With Resected BRAF V600-Mutant Stage III Melanoma.

Author information

1
Axel Hauschild, University Hospital Schleswig-Holstein, Kiel; Dirk Schadendorf, University Hospital Essen, Essen; German Cancer Consortium, Heidelberg, Germany; Reinhard Dummer, University Hospital Zürich Skin Cancer Center, Zürich; Tomas Haas, Novartis AG, Basel, Switzerland; Mario Santinami, Fondazione Istituto Nazionale Tumori, Milan; Mario Mandalà, Papa Giovanni XXIII Cancer Center Hospital, Bergamo; Vanna Chiarion-Sileni, Veneto Institute of Oncology-Istituto di Ricovero e Cura a Carattere Scientifico, Padova, Italy; Victoria Atkinson, Princess Alexandra Hospital; Gallipoli Medical Research Foundation; University of Queensland, Brisbane, Queensland; Andrew Haydon, The Alfred Hospital, Melbourne, Victoria; Richard Kefford, Macquarie University; Westmead Hospital; Richard Kefford and Georgina V. Long, Melanoma Institute Australia; University of Sydney; Royal North Shore and Mater Hospitals, Sydney, New South Wales, Australia; James Larkin, Royal Marsden National Health Service Foundation Trust, London; Ruth Plummer, Freeman Hospital and Newcastle University, Newcastle upon Tyne, United Kingdom; Marta Nyakas, Oslo University Hospital, Oslo, Norway; Caroline Dutriaux, Centre Hospitalier Universitaire de Bordeaux, Hôpital Saint-André, Bordeaux; Caroline Robert, Institute Gustave Roussy, Paris; Laurent Mortier, Université de Lille, Institut National de la Santé et de la Recherche Médicale U1189, Centre Hospitalier Universitaire de sa Region Lille, Lille; Thierry Lesimple, Centre Eugène Marquis, Rennes, France; Jacob Schachter, Sheba Medical Center, Tel Hashomer; Tel Aviv University, Tel Aviv, Israel; Kohinoor Dasgupta, Novartis Healthcare, Hyderabad, India; Mark Shilkrut and Eduard Gasal, Novartis Pharmaceuticals Corporation, East Hanover, NJ; and John M. Kirkwood, UPMC Hillman Cancer Center; University of Pittsburgh, Pittsburgh, PA.

Abstract

PURPOSE:

Dabrafenib plus trametinib improved relapse-free survival (RFS) versus placebo (hazard ratio [HR], 0.47; P < .001) in patients with resected BRAF V600-mutant stage III melanoma (BRF115532; COMBI-AD; ClinicalTrials.gov identifier: NCT01682083). We present an updated RFS analysis on the basis of extended study follow-up and a cure-rate model analysis to estimate the fraction of patients expected to remain relapse free long term.

METHODS:

In this phase III trial, patients with resected BRAF V600-mutant stage III melanoma were randomly assigned to 12 months of adjuvant dabrafenib plus trametinib versus placebo. We report updated RFS (primary end point) and distant metastasis-free survival. RFS was also analyzed by subgroups defined by baseline disease stage (American Joint Committee on Cancer 7th and 8th editions), nodal metastatic burden, and ulceration status. The fraction of patients who remained relapse free long term was estimated using a Weibull mixture cure-rate model.

RESULTS:

At median follow-up of 44 months (dabrafenib plus trametinib) and 42 months (placebo), 3- and 4-year RFS rates were 59% (95% CI, 55% to 64%) and 54% (95% CI, 49% to 59%) in the dabrafenib plus trametinib arm and 40% (95% CI, 35% to 45%) and 38% (95% CI, 34% to 44%) in the placebo arm, respectively (HR, 0.49; 95% CI, 0.40 to 0.59). Distant metastasis-free survival also favored dabrafenib plus trametinib (HR, 0.53; 95% CI, 0.42 to 0.67). The estimated cure rate was 54% (95% CI, 49% to 59%) in the dabrafenib plus trametinib arm compared with 37% (95% CI, 32% to 42%) in the placebo arm. Subgroup analysis of RFS demonstrated similar treatment benefit regardless of baseline factors, including disease stage, nodal metastatic burden, and ulceration.

CONCLUSION:

Longer follow-up confirmed RFS benefit with dabrafenib plus trametinib. Subgroup analysis suggested that dabrafenib plus trametinib benefited patients regardless of baseline factors.

PMID:
30343620
DOI:
10.1200/JCO.18.01219

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