Evidence map›Paper›PMID 28891408›Full record

Trial reportThe New England journal of medicine2017

Adjuvant Dabrafenib plus Trametinib in Stage III BRAF-Mutated Melanoma.

Georgina V Long, Axel Hauschild, Mario Santinami, Victoria Atkinson, Mario Mandalà, Vanna Chiarion-Sileni, James Larkin, Marta Nyakas, Caroline Dutriaux, Andrew Haydon and 13 more

3 registry-linked trialsOpen access · bronzeAbstract readClinical Trial, Phase IIIMulticenter StudyRandomized Controlled Trial
PubMed Publisher
In one paragraph

Trial report in The New England journal of medicine, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to 3 registered trials, which are not on this map. Cited by 664 papers, 6 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
664citing papers in PubMed, 6 pooled it
70.2field-weighted citation impact, top 1% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

NCT01682083 phase3completednot on this map

COMBI-AD: A Phase III Randomized Double Blind Study of Dabrafenib (GSK2118436) in COMBInation With Trametinib (GSK1120212) Versus Two Placebos in the ADjuvant Treatment of High-risk BRAF V600 Mutation-positive Melanoma After Surgical Resection

TypeinterventionalSponsorNovartis PharmaceuticalsRan2013 to 2023Enrolled870ConditionsMelanomaArmsDabrafenib, Trametinib, Placebos
NCT05736523 active not recruitingnot on this mapstarted 2020, after this paper: background citation

Improving Early Detection of Melanoma Recurrence With Circulating Tumor DNA (ctDNA)

TypeobservationalSponsorUniversity of UtahRan2020 to 2025Enrolled28ConditionsMelanoma
NCT06365619 phase2recruitingnot on this mapstarted 2026, after this paper: background citation

Phase II Study of Neoadjuvant Ipilimumab/Nivolumab for Patients With Recurrent, High Risk, Resectable Melanoma

TypeinterventionalSponsorUniversity of UtahRan2026 to 2030Enrolled25ConditionsMelanomaArmsIpilimumab, Nivolumab
3 · Its place in the literature

Who cites it

664 citing papers in PubMed, 6 syntheses or guidelines pooled it, 1,459 citations in OpenAlex.

  1. Pooled it
  2. Pooled it
  3. Cutaneous melanoma: ESMO Clinical Practice Guideline for diagnosis, treatment and follow-up.Annals of oncology : official journal of the European Society for Medical Oncology · 2025
    Guideline
  4. SEOM-GEM clinical guidelines for cutaneous melanoma (2023).Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2024
    Guideline
  5. Guideline
  6. Guideline
  7. Trial
  8. Trial
  9. Trial
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  11. Outcomes With Postrecurrence Systemic Therapy Following Adjuvant Checkpoint Inhibitor Treatment for Resected Melanoma in CheckMate 238.Journal of clinical oncology : official journal of the American Society of Clinical Oncology · 2024
    Trial
  12. Trial
  13. Trial
  14. Review
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604 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

23 authors at 17 institutions in 8 countries.

Georgina V LongFrom the Melanoma Institute Australia, University of Sydney, Royal North Shore and Mater Hospitals (G.V.L.), and Macquarie University, Melanoma Institute Australia, University of Sydney, and Westmead Hospital (R.K.), Sydney, Princess Alexandra Hospital, Gallipoli Medical Research Foundation, University of Queensland, Brisbane (V.A.), and Alfred Hospital, Melbourne, VIC (A. Haydon) - all in Australia; University Hospital Schleswig-Holstein, Kiel (A. Hauschild), and University Hospital Essen, Essen, and the German Cancer Consortium, Heidelberg (D.S.) - all in Germany; Fondazione Istituto Nazionale Tumori, Milan (M.S.), Papa Giovanni XXIII Cancer Center Hospital, Bergamo (M.M.), and the Melanoma Oncology Unit, Veneto Oncology Institute, Padua (V.C.-S.) - all in Italy; Rikshospitalet-Radiumhospitalet, Oslo (M.N.); Centre Hospitalier Universitaire de Bordeaux, Hôpital Saint-André, Bordeaux (C.D.), Institute Gustave Roussy, Paris (C.R.), Université de Lille, INSERM Unité 1189, Centre Hospitalier Régional Universitaire de Lille, Lille (L.M.), and the Medical Oncology Department, Centre Eugène Marquis, Rennes (T.L.) - all in France; Ella Institute for Melanoma, Sheba Medical Center, Tel Hashomer, Israel (J.S.); Royal Marsden NHS Foundation Trust, London (J. Larkin), and Northern Centre for Cancer Care, Freeman Hospital, Newcastle upon Tyne (R.P.) - both in the United Kingdom; Novartis Pharmaceuticals, East Hanover, NJ (R.J., P.Z., B.M., J. Legos); University Hospital Zürich Skin Cancer Center, Zurich, Switzerland (R.D.); and the Melanoma Program, Hillman UPMC Cancer Center, University of Pittsburgh, Pittsburgh (J.M.K.).
Axel HauschildFrom the Melanoma Institute Australia, University of Sydney, Royal North Shore and Mater Hospitals (G.V.L.), and Macquarie University, Melanoma Institute Australia, University of Sydney, and Westmead Hospital (R.K.), Sydney, Princess Alexandra Hospital, Gallipoli Medical Research Foundation, University of Queensland, Brisbane (V.A.), and Alfred Hospital, Melbourne, VIC (A. Haydon) - all in Australia; University Hospital Schleswig-Holstein, Kiel (A. Hauschild), and University Hospital Essen, Essen, and the German Cancer Consortium, Heidelberg (D.S.) - all in Germany; Fondazione Istituto Nazionale Tumori, Milan (M.S.), Papa Giovanni XXIII Cancer Center Hospital, Bergamo (M.M.), and the Melanoma Oncology Unit, Veneto Oncology Institute, Padua (V.C.-S.) - all in Italy; Rikshospitalet-Radiumhospitalet, Oslo (M.N.); Centre Hospitalier Universitaire de Bordeaux, Hôpital Saint-André, Bordeaux (C.D.), Institute Gustave Roussy, Paris (C.R.), Université de Lille, INSERM Unité 1189, Centre Hospitalier Régional Universitaire de Lille, Lille (L.M.), and the Medical Oncology Department, Centre Eugène Marquis, Rennes (T.L.) - all in France; Ella Institute for Melanoma, Sheba Medical Center, Tel Hashomer, Israel (J.S.); Royal Marsden NHS Foundation Trust, London (J. Larkin), and Northern Centre for Cancer Care, Freeman Hospital, Newcastle upon Tyne (R.P.) - both in the United Kingdom; Novartis Pharmaceuticals, East Hanover, NJ (R.J., P.Z., B.M., J. Legos); University Hospital Zürich Skin Cancer Center, Zurich, Switzerland (R.D.); and the Melanoma Program, Hillman UPMC Cancer Center, University of Pittsburgh, Pittsburgh (J.M.K.).
Mario SantinamiFrom the Melanoma Institute Australia, University of Sydney, Royal North Shore and Mater Hospitals (G.V.L.), and Macquarie University, Melanoma Institute Australia, University of Sydney, and Westmead Hospital (R.K.), Sydney, Princess Alexandra Hospital, Gallipoli Medical Research Foundation, University of Queensland, Brisbane (V.A.), and Alfred Hospital, Melbourne, VIC (A. Haydon) - all in Australia; University Hospital Schleswig-Holstein, Kiel (A. Hauschild), and University Hospital Essen, Essen, and the German Cancer Consortium, Heidelberg (D.S.) - all in Germany; Fondazione Istituto Nazionale Tumori, Milan (M.S.), Papa Giovanni XXIII Cancer Center Hospital, Bergamo (M.M.), and the Melanoma Oncology Unit, Veneto Oncology Institute, Padua (V.C.-S.) - all in Italy; Rikshospitalet-Radiumhospitalet, Oslo (M.N.); Centre Hospitalier Universitaire de Bordeaux, Hôpital Saint-André, Bordeaux (C.D.), Institute Gustave Roussy, Paris (C.R.), Université de Lille, INSERM Unité 1189, Centre Hospitalier Régional Universitaire de Lille, Lille (L.M.), and the Medical Oncology Department, Centre Eugène Marquis, Rennes (T.L.) - all in France; Ella Institute for Melanoma, Sheba Medical Center, Tel Hashomer, Israel (J.S.); Royal Marsden NHS Foundation Trust, London (J. Larkin), and Northern Centre for Cancer Care, Freeman Hospital, Newcastle upon Tyne (R.P.) - both in the United Kingdom; Novartis Pharmaceuticals, East Hanover, NJ (R.J., P.Z., B.M., J. Legos); University Hospital Zürich Skin Cancer Center, Zurich, Switzerland (R.D.); and the Melanoma Program, Hillman UPMC Cancer Center, University of Pittsburgh, Pittsburgh (J.M.K.).
Victoria AtkinsonFrom the Melanoma Institute Australia, University of Sydney, Royal North Shore and Mater Hospitals (G.V.L.), and Macquarie University, Melanoma Institute Australia, University of Sydney, and Westmead Hospital (R.K.), Sydney, Princess Alexandra Hospital, Gallipoli Medical Research Foundation, University of Queensland, Brisbane (V.A.), and Alfred Hospital, Melbourne, VIC (A. Haydon) - all in Australia; University Hospital Schleswig-Holstein, Kiel (A. Hauschild), and University Hospital Essen, Essen, and the German Cancer Consortium, Heidelberg (D.S.) - all in Germany; Fondazione Istituto Nazionale Tumori, Milan (M.S.), Papa Giovanni XXIII Cancer Center Hospital, Bergamo (M.M.), and the Melanoma Oncology Unit, Veneto Oncology Institute, Padua (V.C.-S.) - all in Italy; Rikshospitalet-Radiumhospitalet, Oslo (M.N.); Centre Hospitalier Universitaire de Bordeaux, Hôpital Saint-André, Bordeaux (C.D.), Institute Gustave Roussy, Paris (C.R.), Université de Lille, INSERM Unité 1189, Centre Hospitalier Régional Universitaire de Lille, Lille (L.M.), and the Medical Oncology Department, Centre Eugène Marquis, Rennes (T.L.) - all in France; Ella Institute for Melanoma, Sheba Medical Center, Tel Hashomer, Israel (J.S.); Royal Marsden NHS Foundation Trust, London (J. Larkin), and Northern Centre for Cancer Care, Freeman Hospital, Newcastle upon Tyne (R.P.) - both in the United Kingdom; Novartis Pharmaceuticals, East Hanover, NJ (R.J., P.Z., B.M., J. Legos); University Hospital Zürich Skin Cancer Center, Zurich, Switzerland (R.D.); and the Melanoma Program, Hillman UPMC Cancer Center, University of Pittsburgh, Pittsburgh (J.M.K.).
Mario MandalàFrom the Melanoma Institute Australia, University of Sydney, Royal North Shore and Mater Hospitals (G.V.L.), and Macquarie University, Melanoma Institute Australia, University of Sydney, and Westmead Hospital (R.K.), Sydney, Princess Alexandra Hospital, Gallipoli Medical Research Foundation, University of Queensland, Brisbane (V.A.), and Alfred Hospital, Melbourne, VIC (A. Haydon) - all in Australia; University Hospital Schleswig-Holstein, Kiel (A. Hauschild), and University Hospital Essen, Essen, and the German Cancer Consortium, Heidelberg (D.S.) - all in Germany; Fondazione Istituto Nazionale Tumori, Milan (M.S.), Papa Giovanni XXIII Cancer Center Hospital, Bergamo (M.M.), and the Melanoma Oncology Unit, Veneto Oncology Institute, Padua (V.C.-S.) - all in Italy; Rikshospitalet-Radiumhospitalet, Oslo (M.N.); Centre Hospitalier Universitaire de Bordeaux, Hôpital Saint-André, Bordeaux (C.D.), Institute Gustave Roussy, Paris (C.R.), Université de Lille, INSERM Unité 1189, Centre Hospitalier Régional Universitaire de Lille, Lille (L.M.), and the Medical Oncology Department, Centre Eugène Marquis, Rennes (T.L.) - all in France; Ella Institute for Melanoma, Sheba Medical Center, Tel Hashomer, Israel (J.S.); Royal Marsden NHS Foundation Trust, London (J. Larkin), and Northern Centre for Cancer Care, Freeman Hospital, Newcastle upon Tyne (R.P.) - both in the United Kingdom; Novartis Pharmaceuticals, East Hanover, NJ (R.J., P.Z., B.M., J. Legos); University Hospital Zürich Skin Cancer Center, Zurich, Switzerland (R.D.); and the Melanoma Program, Hillman UPMC Cancer Center, University of Pittsburgh, Pittsburgh (J.M.K.).
Vanna Chiarion-SileniFrom the Melanoma Institute Australia, University of Sydney, Royal North Shore and Mater Hospitals (G.V.L.), and Macquarie University, Melanoma Institute Australia, University of Sydney, and Westmead Hospital (R.K.), Sydney, Princess Alexandra Hospital, Gallipoli Medical Research Foundation, University of Queensland, Brisbane (V.A.), and Alfred Hospital, Melbourne, VIC (A. Haydon) - all in Australia; University Hospital Schleswig-Holstein, Kiel (A. Hauschild), and University Hospital Essen, Essen, and the German Cancer Consortium, Heidelberg (D.S.) - all in Germany; Fondazione Istituto Nazionale Tumori, Milan (M.S.), Papa Giovanni XXIII Cancer Center Hospital, Bergamo (M.M.), and the Melanoma Oncology Unit, Veneto Oncology Institute, Padua (V.C.-S.) - all in Italy; Rikshospitalet-Radiumhospitalet, Oslo (M.N.); Centre Hospitalier Universitaire de Bordeaux, Hôpital Saint-André, Bordeaux (C.D.), Institute Gustave Roussy, Paris (C.R.), Université de Lille, INSERM Unité 1189, Centre Hospitalier Régional Universitaire de Lille, Lille (L.M.), and the Medical Oncology Department, Centre Eugène Marquis, Rennes (T.L.) - all in France; Ella Institute for Melanoma, Sheba Medical Center, Tel Hashomer, Israel (J.S.); Royal Marsden NHS Foundation Trust, London (J. Larkin), and Northern Centre for Cancer Care, Freeman Hospital, Newcastle upon Tyne (R.P.) - both in the United Kingdom; Novartis Pharmaceuticals, East Hanover, NJ (R.J., P.Z., B.M., J. Legos); University Hospital Zürich Skin Cancer Center, Zurich, Switzerland (R.D.); and the Melanoma Program, Hillman UPMC Cancer Center, University of Pittsburgh, Pittsburgh (J.M.K.).
James LarkinFrom the Melanoma Institute Australia, University of Sydney, Royal North Shore and Mater Hospitals (G.V.L.), and Macquarie University, Melanoma Institute Australia, University of Sydney, and Westmead Hospital (R.K.), Sydney, Princess Alexandra Hospital, Gallipoli Medical Research Foundation, University of Queensland, Brisbane (V.A.), and Alfred Hospital, Melbourne, VIC (A. Haydon) - all in Australia; University Hospital Schleswig-Holstein, Kiel (A. Hauschild), and University Hospital Essen, Essen, and the German Cancer Consortium, Heidelberg (D.S.) - all in Germany; Fondazione Istituto Nazionale Tumori, Milan (M.S.), Papa Giovanni XXIII Cancer Center Hospital, Bergamo (M.M.), and the Melanoma Oncology Unit, Veneto Oncology Institute, Padua (V.C.-S.) - all in Italy; Rikshospitalet-Radiumhospitalet, Oslo (M.N.); Centre Hospitalier Universitaire de Bordeaux, Hôpital Saint-André, Bordeaux (C.D.), Institute Gustave Roussy, Paris (C.R.), Université de Lille, INSERM Unité 1189, Centre Hospitalier Régional Universitaire de Lille, Lille (L.M.), and the Medical Oncology Department, Centre Eugène Marquis, Rennes (T.L.) - all in France; Ella Institute for Melanoma, Sheba Medical Center, Tel Hashomer, Israel (J.S.); Royal Marsden NHS Foundation Trust, London (J. Larkin), and Northern Centre for Cancer Care, Freeman Hospital, Newcastle upon Tyne (R.P.) - both in the United Kingdom; Novartis Pharmaceuticals, East Hanover, NJ (R.J., P.Z., B.M., J. Legos); University Hospital Zürich Skin Cancer Center, Zurich, Switzerland (R.D.); and the Melanoma Program, Hillman UPMC Cancer Center, University of Pittsburgh, Pittsburgh (J.M.K.).
Marta NyakasFrom the Melanoma Institute Australia, University of Sydney, Royal North Shore and Mater Hospitals (G.V.L.), and Macquarie University, Melanoma Institute Australia, University of Sydney, and Westmead Hospital (R.K.), Sydney, Princess Alexandra Hospital, Gallipoli Medical Research Foundation, University of Queensland, Brisbane (V.A.), and Alfred Hospital, Melbourne, VIC (A. Haydon) - all in Australia; University Hospital Schleswig-Holstein, Kiel (A. Hauschild), and University Hospital Essen, Essen, and the German Cancer Consortium, Heidelberg (D.S.) - all in Germany; Fondazione Istituto Nazionale Tumori, Milan (M.S.), Papa Giovanni XXIII Cancer Center Hospital, Bergamo (M.M.), and the Melanoma Oncology Unit, Veneto Oncology Institute, Padua (V.C.-S.) - all in Italy; Rikshospitalet-Radiumhospitalet, Oslo (M.N.); Centre Hospitalier Universitaire de Bordeaux, Hôpital Saint-André, Bordeaux (C.D.), Institute Gustave Roussy, Paris (C.R.), Université de Lille, INSERM Unité 1189, Centre Hospitalier Régional Universitaire de Lille, Lille (L.M.), and the Medical Oncology Department, Centre Eugène Marquis, Rennes (T.L.) - all in France; Ella Institute for Melanoma, Sheba Medical Center, Tel Hashomer, Israel (J.S.); Royal Marsden NHS Foundation Trust, London (J. Larkin), and Northern Centre for Cancer Care, Freeman Hospital, Newcastle upon Tyne (R.P.) - both in the United Kingdom; Novartis Pharmaceuticals, East Hanover, NJ (R.J., P.Z., B.M., J. Legos); University Hospital Zürich Skin Cancer Center, Zurich, Switzerland (R.D.); and the Melanoma Program, Hillman UPMC Cancer Center, University of Pittsburgh, Pittsburgh (J.M.K.).
Caroline DutriauxFrom the Melanoma Institute Australia, University of Sydney, Royal North Shore and Mater Hospitals (G.V.L.), and Macquarie University, Melanoma Institute Australia, University of Sydney, and Westmead Hospital (R.K.), Sydney, Princess Alexandra Hospital, Gallipoli Medical Research Foundation, University of Queensland, Brisbane (V.A.), and Alfred Hospital, Melbourne, VIC (A. Haydon) - all in Australia; University Hospital Schleswig-Holstein, Kiel (A. Hauschild), and University Hospital Essen, Essen, and the German Cancer Consortium, Heidelberg (D.S.) - all in Germany; Fondazione Istituto Nazionale Tumori, Milan (M.S.), Papa Giovanni XXIII Cancer Center Hospital, Bergamo (M.M.), and the Melanoma Oncology Unit, Veneto Oncology Institute, Padua (V.C.-S.) - all in Italy; Rikshospitalet-Radiumhospitalet, Oslo (M.N.); Centre Hospitalier Universitaire de Bordeaux, Hôpital Saint-André, Bordeaux (C.D.), Institute Gustave Roussy, Paris (C.R.), Université de Lille, INSERM Unité 1189, Centre Hospitalier Régional Universitaire de Lille, Lille (L.M.), and the Medical Oncology Department, Centre Eugène Marquis, Rennes (T.L.) - all in France; Ella Institute for Melanoma, Sheba Medical Center, Tel Hashomer, Israel (J.S.); Royal Marsden NHS Foundation Trust, London (J. Larkin), and Northern Centre for Cancer Care, Freeman Hospital, Newcastle upon Tyne (R.P.) - both in the United Kingdom; Novartis Pharmaceuticals, East Hanover, NJ (R.J., P.Z., B.M., J. Legos); University Hospital Zürich Skin Cancer Center, Zurich, Switzerland (R.D.); and the Melanoma Program, Hillman UPMC Cancer Center, University of Pittsburgh, Pittsburgh (J.M.K.).
Andrew HaydonFrom the Melanoma Institute Australia, University of Sydney, Royal North Shore and Mater Hospitals (G.V.L.), and Macquarie University, Melanoma Institute Australia, University of Sydney, and Westmead Hospital (R.K.), Sydney, Princess Alexandra Hospital, Gallipoli Medical Research Foundation, University of Queensland, Brisbane (V.A.), and Alfred Hospital, Melbourne, VIC (A. Haydon) - all in Australia; University Hospital Schleswig-Holstein, Kiel (A. Hauschild), and University Hospital Essen, Essen, and the German Cancer Consortium, Heidelberg (D.S.) - all in Germany; Fondazione Istituto Nazionale Tumori, Milan (M.S.), Papa Giovanni XXIII Cancer Center Hospital, Bergamo (M.M.), and the Melanoma Oncology Unit, Veneto Oncology Institute, Padua (V.C.-S.) - all in Italy; Rikshospitalet-Radiumhospitalet, Oslo (M.N.); Centre Hospitalier Universitaire de Bordeaux, Hôpital Saint-André, Bordeaux (C.D.), Institute Gustave Roussy, Paris (C.R.), Université de Lille, INSERM Unité 1189, Centre Hospitalier Régional Universitaire de Lille, Lille (L.M.), and the Medical Oncology Department, Centre Eugène Marquis, Rennes (T.L.) - all in France; Ella Institute for Melanoma, Sheba Medical Center, Tel Hashomer, Israel (J.S.); Royal Marsden NHS Foundation Trust, London (J. Larkin), and Northern Centre for Cancer Care, Freeman Hospital, Newcastle upon Tyne (R.P.) - both in the United Kingdom; Novartis Pharmaceuticals, East Hanover, NJ (R.J., P.Z., B.M., J. Legos); University Hospital Zürich Skin Cancer Center, Zurich, Switzerland (R.D.); and the Melanoma Program, Hillman UPMC Cancer Center, University of Pittsburgh, Pittsburgh (J.M.K.).
Caroline RobertFrom the Melanoma Institute Australia, University of Sydney, Royal North Shore and Mater Hospitals (G.V.L.), and Macquarie University, Melanoma Institute Australia, University of Sydney, and Westmead Hospital (R.K.), Sydney, Princess Alexandra Hospital, Gallipoli Medical Research Foundation, University of Queensland, Brisbane (V.A.), and Alfred Hospital, Melbourne, VIC (A. Haydon) - all in Australia; University Hospital Schleswig-Holstein, Kiel (A. Hauschild), and University Hospital Essen, Essen, and the German Cancer Consortium, Heidelberg (D.S.) - all in Germany; Fondazione Istituto Nazionale Tumori, Milan (M.S.), Papa Giovanni XXIII Cancer Center Hospital, Bergamo (M.M.), and the Melanoma Oncology Unit, Veneto Oncology Institute, Padua (V.C.-S.) - all in Italy; Rikshospitalet-Radiumhospitalet, Oslo (M.N.); Centre Hospitalier Universitaire de Bordeaux, Hôpital Saint-André, Bordeaux (C.D.), Institute Gustave Roussy, Paris (C.R.), Université de Lille, INSERM Unité 1189, Centre Hospitalier Régional Universitaire de Lille, Lille (L.M.), and the Medical Oncology Department, Centre Eugène Marquis, Rennes (T.L.) - all in France; Ella Institute for Melanoma, Sheba Medical Center, Tel Hashomer, Israel (J.S.); Royal Marsden NHS Foundation Trust, London (J. Larkin), and Northern Centre for Cancer Care, Freeman Hospital, Newcastle upon Tyne (R.P.) - both in the United Kingdom; Novartis Pharmaceuticals, East Hanover, NJ (R.J., P.Z., B.M., J. Legos); University Hospital Zürich Skin Cancer Center, Zurich, Switzerland (R.D.); and the Melanoma Program, Hillman UPMC Cancer Center, University of Pittsburgh, Pittsburgh (J.M.K.).
Laurent MortierFrom the Melanoma Institute Australia, University of Sydney, Royal North Shore and Mater Hospitals (G.V.L.), and Macquarie University, Melanoma Institute Australia, University of Sydney, and Westmead Hospital (R.K.), Sydney, Princess Alexandra Hospital, Gallipoli Medical Research Foundation, University of Queensland, Brisbane (V.A.), and Alfred Hospital, Melbourne, VIC (A. Haydon) - all in Australia; University Hospital Schleswig-Holstein, Kiel (A. Hauschild), and University Hospital Essen, Essen, and the German Cancer Consortium, Heidelberg (D.S.) - all in Germany; Fondazione Istituto Nazionale Tumori, Milan (M.S.), Papa Giovanni XXIII Cancer Center Hospital, Bergamo (M.M.), and the Melanoma Oncology Unit, Veneto Oncology Institute, Padua (V.C.-S.) - all in Italy; Rikshospitalet-Radiumhospitalet, Oslo (M.N.); Centre Hospitalier Universitaire de Bordeaux, Hôpital Saint-André, Bordeaux (C.D.), Institute Gustave Roussy, Paris (C.R.), Université de Lille, INSERM Unité 1189, Centre Hospitalier Régional Universitaire de Lille, Lille (L.M.), and the Medical Oncology Department, Centre Eugène Marquis, Rennes (T.L.) - all in France; Ella Institute for Melanoma, Sheba Medical Center, Tel Hashomer, Israel (J.S.); Royal Marsden NHS Foundation Trust, London (J. Larkin), and Northern Centre for Cancer Care, Freeman Hospital, Newcastle upon Tyne (R.P.) - both in the United Kingdom; Novartis Pharmaceuticals, East Hanover, NJ (R.J., P.Z., B.M., J. Legos); University Hospital Zürich Skin Cancer Center, Zurich, Switzerland (R.D.); and the Melanoma Program, Hillman UPMC Cancer Center, University of Pittsburgh, Pittsburgh (J.M.K.).
Jacob SchachterFrom the Melanoma Institute Australia, University of Sydney, Royal North Shore and Mater Hospitals (G.V.L.), and Macquarie University, Melanoma Institute Australia, University of Sydney, and Westmead Hospital (R.K.), Sydney, Princess Alexandra Hospital, Gallipoli Medical Research Foundation, University of Queensland, Brisbane (V.A.), and Alfred Hospital, Melbourne, VIC (A. Haydon) - all in Australia; University Hospital Schleswig-Holstein, Kiel (A. Hauschild), and University Hospital Essen, Essen, and the German Cancer Consortium, Heidelberg (D.S.) - all in Germany; Fondazione Istituto Nazionale Tumori, Milan (M.S.), Papa Giovanni XXIII Cancer Center Hospital, Bergamo (M.M.), and the Melanoma Oncology Unit, Veneto Oncology Institute, Padua (V.C.-S.) - all in Italy; Rikshospitalet-Radiumhospitalet, Oslo (M.N.); Centre Hospitalier Universitaire de Bordeaux, Hôpital Saint-André, Bordeaux (C.D.), Institute Gustave Roussy, Paris (C.R.), Université de Lille, INSERM Unité 1189, Centre Hospitalier Régional Universitaire de Lille, Lille (L.M.), and the Medical Oncology Department, Centre Eugène Marquis, Rennes (T.L.) - all in France; Ella Institute for Melanoma, Sheba Medical Center, Tel Hashomer, Israel (J.S.); Royal Marsden NHS Foundation Trust, London (J. Larkin), and Northern Centre for Cancer Care, Freeman Hospital, Newcastle upon Tyne (R.P.) - both in the United Kingdom; Novartis Pharmaceuticals, East Hanover, NJ (R.J., P.Z., B.M., J. Legos); University Hospital Zürich Skin Cancer Center, Zurich, Switzerland (R.D.); and the Melanoma Program, Hillman UPMC Cancer Center, University of Pittsburgh, Pittsburgh (J.M.K.).
Dirk SchadendorfFrom the Melanoma Institute Australia, University of Sydney, Royal North Shore and Mater Hospitals (G.V.L.), and Macquarie University, Melanoma Institute Australia, University of Sydney, and Westmead Hospital (R.K.), Sydney, Princess Alexandra Hospital, Gallipoli Medical Research Foundation, University of Queensland, Brisbane (V.A.), and Alfred Hospital, Melbourne, VIC (A. Haydon) - all in Australia; University Hospital Schleswig-Holstein, Kiel (A. Hauschild), and University Hospital Essen, Essen, and the German Cancer Consortium, Heidelberg (D.S.) - all in Germany; Fondazione Istituto Nazionale Tumori, Milan (M.S.), Papa Giovanni XXIII Cancer Center Hospital, Bergamo (M.M.), and the Melanoma Oncology Unit, Veneto Oncology Institute, Padua (V.C.-S.) - all in Italy; Rikshospitalet-Radiumhospitalet, Oslo (M.N.); Centre Hospitalier Universitaire de Bordeaux, Hôpital Saint-André, Bordeaux (C.D.), Institute Gustave Roussy, Paris (C.R.), Université de Lille, INSERM Unité 1189, Centre Hospitalier Régional Universitaire de Lille, Lille (L.M.), and the Medical Oncology Department, Centre Eugène Marquis, Rennes (T.L.) - all in France; Ella Institute for Melanoma, Sheba Medical Center, Tel Hashomer, Israel (J.S.); Royal Marsden NHS Foundation Trust, London (J. Larkin), and Northern Centre for Cancer Care, Freeman Hospital, Newcastle upon Tyne (R.P.) - both in the United Kingdom; Novartis Pharmaceuticals, East Hanover, NJ (R.J., P.Z., B.M., J. Legos); University Hospital Zürich Skin Cancer Center, Zurich, Switzerland (R.D.); and the Melanoma Program, Hillman UPMC Cancer Center, University of Pittsburgh, Pittsburgh (J.M.K.).
Thierry LesimpleFrom the Melanoma Institute Australia, University of Sydney, Royal North Shore and Mater Hospitals (G.V.L.), and Macquarie University, Melanoma Institute Australia, University of Sydney, and Westmead Hospital (R.K.), Sydney, Princess Alexandra Hospital, Gallipoli Medical Research Foundation, University of Queensland, Brisbane (V.A.), and Alfred Hospital, Melbourne, VIC (A. Haydon) - all in Australia; University Hospital Schleswig-Holstein, Kiel (A. Hauschild), and University Hospital Essen, Essen, and the German Cancer Consortium, Heidelberg (D.S.) - all in Germany; Fondazione Istituto Nazionale Tumori, Milan (M.S.), Papa Giovanni XXIII Cancer Center Hospital, Bergamo (M.M.), and the Melanoma Oncology Unit, Veneto Oncology Institute, Padua (V.C.-S.) - all in Italy; Rikshospitalet-Radiumhospitalet, Oslo (M.N.); Centre Hospitalier Universitaire de Bordeaux, Hôpital Saint-André, Bordeaux (C.D.), Institute Gustave Roussy, Paris (C.R.), Université de Lille, INSERM Unité 1189, Centre Hospitalier Régional Universitaire de Lille, Lille (L.M.), and the Medical Oncology Department, Centre Eugène Marquis, Rennes (T.L.) - all in France; Ella Institute for Melanoma, Sheba Medical Center, Tel Hashomer, Israel (J.S.); Royal Marsden NHS Foundation Trust, London (J. Larkin), and Northern Centre for Cancer Care, Freeman Hospital, Newcastle upon Tyne (R.P.) - both in the United Kingdom; Novartis Pharmaceuticals, East Hanover, NJ (R.J., P.Z., B.M., J. Legos); University Hospital Zürich Skin Cancer Center, Zurich, Switzerland (R.D.); and the Melanoma Program, Hillman UPMC Cancer Center, University of Pittsburgh, Pittsburgh (J.M.K.).
Ruth PlummerFrom the Melanoma Institute Australia, University of Sydney, Royal North Shore and Mater Hospitals (G.V.L.), and Macquarie University, Melanoma Institute Australia, University of Sydney, and Westmead Hospital (R.K.), Sydney, Princess Alexandra Hospital, Gallipoli Medical Research Foundation, University of Queensland, Brisbane (V.A.), and Alfred Hospital, Melbourne, VIC (A. Haydon) - all in Australia; University Hospital Schleswig-Holstein, Kiel (A. Hauschild), and University Hospital Essen, Essen, and the German Cancer Consortium, Heidelberg (D.S.) - all in Germany; Fondazione Istituto Nazionale Tumori, Milan (M.S.), Papa Giovanni XXIII Cancer Center Hospital, Bergamo (M.M.), and the Melanoma Oncology Unit, Veneto Oncology Institute, Padua (V.C.-S.) - all in Italy; Rikshospitalet-Radiumhospitalet, Oslo (M.N.); Centre Hospitalier Universitaire de Bordeaux, Hôpital Saint-André, Bordeaux (C.D.), Institute Gustave Roussy, Paris (C.R.), Université de Lille, INSERM Unité 1189, Centre Hospitalier Régional Universitaire de Lille, Lille (L.M.), and the Medical Oncology Department, Centre Eugène Marquis, Rennes (T.L.) - all in France; Ella Institute for Melanoma, Sheba Medical Center, Tel Hashomer, Israel (J.S.); Royal Marsden NHS Foundation Trust, London (J. Larkin), and Northern Centre for Cancer Care, Freeman Hospital, Newcastle upon Tyne (R.P.) - both in the United Kingdom; Novartis Pharmaceuticals, East Hanover, NJ (R.J., P.Z., B.M., J. Legos); University Hospital Zürich Skin Cancer Center, Zurich, Switzerland (R.D.); and the Melanoma Program, Hillman UPMC Cancer Center, University of Pittsburgh, Pittsburgh (J.M.K.).
Ran JiFrom the Melanoma Institute Australia, University of Sydney, Royal North Shore and Mater Hospitals (G.V.L.), and Macquarie University, Melanoma Institute Australia, University of Sydney, and Westmead Hospital (R.K.), Sydney, Princess Alexandra Hospital, Gallipoli Medical Research Foundation, University of Queensland, Brisbane (V.A.), and Alfred Hospital, Melbourne, VIC (A. Haydon) - all in Australia; University Hospital Schleswig-Holstein, Kiel (A. Hauschild), and University Hospital Essen, Essen, and the German Cancer Consortium, Heidelberg (D.S.) - all in Germany; Fondazione Istituto Nazionale Tumori, Milan (M.S.), Papa Giovanni XXIII Cancer Center Hospital, Bergamo (M.M.), and the Melanoma Oncology Unit, Veneto Oncology Institute, Padua (V.C.-S.) - all in Italy; Rikshospitalet-Radiumhospitalet, Oslo (M.N.); Centre Hospitalier Universitaire de Bordeaux, Hôpital Saint-André, Bordeaux (C.D.), Institute Gustave Roussy, Paris (C.R.), Université de Lille, INSERM Unité 1189, Centre Hospitalier Régional Universitaire de Lille, Lille (L.M.), and the Medical Oncology Department, Centre Eugène Marquis, Rennes (T.L.) - all in France; Ella Institute for Melanoma, Sheba Medical Center, Tel Hashomer, Israel (J.S.); Royal Marsden NHS Foundation Trust, London (J. Larkin), and Northern Centre for Cancer Care, Freeman Hospital, Newcastle upon Tyne (R.P.) - both in the United Kingdom; Novartis Pharmaceuticals, East Hanover, NJ (R.J., P.Z., B.M., J. Legos); University Hospital Zürich Skin Cancer Center, Zurich, Switzerland (R.D.); and the Melanoma Program, Hillman UPMC Cancer Center, University of Pittsburgh, Pittsburgh (J.M.K.).
Pingkuan ZhangFrom the Melanoma Institute Australia, University of Sydney, Royal North Shore and Mater Hospitals (G.V.L.), and Macquarie University, Melanoma Institute Australia, University of Sydney, and Westmead Hospital (R.K.), Sydney, Princess Alexandra Hospital, Gallipoli Medical Research Foundation, University of Queensland, Brisbane (V.A.), and Alfred Hospital, Melbourne, VIC (A. Haydon) - all in Australia; University Hospital Schleswig-Holstein, Kiel (A. Hauschild), and University Hospital Essen, Essen, and the German Cancer Consortium, Heidelberg (D.S.) - all in Germany; Fondazione Istituto Nazionale Tumori, Milan (M.S.), Papa Giovanni XXIII Cancer Center Hospital, Bergamo (M.M.), and the Melanoma Oncology Unit, Veneto Oncology Institute, Padua (V.C.-S.) - all in Italy; Rikshospitalet-Radiumhospitalet, Oslo (M.N.); Centre Hospitalier Universitaire de Bordeaux, Hôpital Saint-André, Bordeaux (C.D.), Institute Gustave Roussy, Paris (C.R.), Université de Lille, INSERM Unité 1189, Centre Hospitalier Régional Universitaire de Lille, Lille (L.M.), and the Medical Oncology Department, Centre Eugène Marquis, Rennes (T.L.) - all in France; Ella Institute for Melanoma, Sheba Medical Center, Tel Hashomer, Israel (J.S.); Royal Marsden NHS Foundation Trust, London (J. Larkin), and Northern Centre for Cancer Care, Freeman Hospital, Newcastle upon Tyne (R.P.) - both in the United Kingdom; Novartis Pharmaceuticals, East Hanover, NJ (R.J., P.Z., B.M., J. Legos); University Hospital Zürich Skin Cancer Center, Zurich, Switzerland (R.D.); and the Melanoma Program, Hillman UPMC Cancer Center, University of Pittsburgh, Pittsburgh (J.M.K.).
Bijoyesh MookerjeeFrom the Melanoma Institute Australia, University of Sydney, Royal North Shore and Mater Hospitals (G.V.L.), and Macquarie University, Melanoma Institute Australia, University of Sydney, and Westmead Hospital (R.K.), Sydney, Princess Alexandra Hospital, Gallipoli Medical Research Foundation, University of Queensland, Brisbane (V.A.), and Alfred Hospital, Melbourne, VIC (A. Haydon) - all in Australia; University Hospital Schleswig-Holstein, Kiel (A. Hauschild), and University Hospital Essen, Essen, and the German Cancer Consortium, Heidelberg (D.S.) - all in Germany; Fondazione Istituto Nazionale Tumori, Milan (M.S.), Papa Giovanni XXIII Cancer Center Hospital, Bergamo (M.M.), and the Melanoma Oncology Unit, Veneto Oncology Institute, Padua (V.C.-S.) - all in Italy; Rikshospitalet-Radiumhospitalet, Oslo (M.N.); Centre Hospitalier Universitaire de Bordeaux, Hôpital Saint-André, Bordeaux (C.D.), Institute Gustave Roussy, Paris (C.R.), Université de Lille, INSERM Unité 1189, Centre Hospitalier Régional Universitaire de Lille, Lille (L.M.), and the Medical Oncology Department, Centre Eugène Marquis, Rennes (T.L.) - all in France; Ella Institute for Melanoma, Sheba Medical Center, Tel Hashomer, Israel (J.S.); Royal Marsden NHS Foundation Trust, London (J. Larkin), and Northern Centre for Cancer Care, Freeman Hospital, Newcastle upon Tyne (R.P.) - both in the United Kingdom; Novartis Pharmaceuticals, East Hanover, NJ (R.J., P.Z., B.M., J. Legos); University Hospital Zürich Skin Cancer Center, Zurich, Switzerland (R.D.); and the Melanoma Program, Hillman UPMC Cancer Center, University of Pittsburgh, Pittsburgh (J.M.K.).
Jeff LegosFrom the Melanoma Institute Australia, University of Sydney, Royal North Shore and Mater Hospitals (G.V.L.), and Macquarie University, Melanoma Institute Australia, University of Sydney, and Westmead Hospital (R.K.), Sydney, Princess Alexandra Hospital, Gallipoli Medical Research Foundation, University of Queensland, Brisbane (V.A.), and Alfred Hospital, Melbourne, VIC (A. Haydon) - all in Australia; University Hospital Schleswig-Holstein, Kiel (A. Hauschild), and University Hospital Essen, Essen, and the German Cancer Consortium, Heidelberg (D.S.) - all in Germany; Fondazione Istituto Nazionale Tumori, Milan (M.S.), Papa Giovanni XXIII Cancer Center Hospital, Bergamo (M.M.), and the Melanoma Oncology Unit, Veneto Oncology Institute, Padua (V.C.-S.) - all in Italy; Rikshospitalet-Radiumhospitalet, Oslo (M.N.); Centre Hospitalier Universitaire de Bordeaux, Hôpital Saint-André, Bordeaux (C.D.), Institute Gustave Roussy, Paris (C.R.), Université de Lille, INSERM Unité 1189, Centre Hospitalier Régional Universitaire de Lille, Lille (L.M.), and the Medical Oncology Department, Centre Eugène Marquis, Rennes (T.L.) - all in France; Ella Institute for Melanoma, Sheba Medical Center, Tel Hashomer, Israel (J.S.); Royal Marsden NHS Foundation Trust, London (J. Larkin), and Northern Centre for Cancer Care, Freeman Hospital, Newcastle upon Tyne (R.P.) - both in the United Kingdom; Novartis Pharmaceuticals, East Hanover, NJ (R.J., P.Z., B.M., J. Legos); University Hospital Zürich Skin Cancer Center, Zurich, Switzerland (R.D.); and the Melanoma Program, Hillman UPMC Cancer Center, University of Pittsburgh, Pittsburgh (J.M.K.).
Richard KeffordFrom the Melanoma Institute Australia, University of Sydney, Royal North Shore and Mater Hospitals (G.V.L.), and Macquarie University, Melanoma Institute Australia, University of Sydney, and Westmead Hospital (R.K.), Sydney, Princess Alexandra Hospital, Gallipoli Medical Research Foundation, University of Queensland, Brisbane (V.A.), and Alfred Hospital, Melbourne, VIC (A. Haydon) - all in Australia; University Hospital Schleswig-Holstein, Kiel (A. Hauschild), and University Hospital Essen, Essen, and the German Cancer Consortium, Heidelberg (D.S.) - all in Germany; Fondazione Istituto Nazionale Tumori, Milan (M.S.), Papa Giovanni XXIII Cancer Center Hospital, Bergamo (M.M.), and the Melanoma Oncology Unit, Veneto Oncology Institute, Padua (V.C.-S.) - all in Italy; Rikshospitalet-Radiumhospitalet, Oslo (M.N.); Centre Hospitalier Universitaire de Bordeaux, Hôpital Saint-André, Bordeaux (C.D.), Institute Gustave Roussy, Paris (C.R.), Université de Lille, INSERM Unité 1189, Centre Hospitalier Régional Universitaire de Lille, Lille (L.M.), and the Medical Oncology Department, Centre Eugène Marquis, Rennes (T.L.) - all in France; Ella Institute for Melanoma, Sheba Medical Center, Tel Hashomer, Israel (J.S.); Royal Marsden NHS Foundation Trust, London (J. Larkin), and Northern Centre for Cancer Care, Freeman Hospital, Newcastle upon Tyne (R.P.) - both in the United Kingdom; Novartis Pharmaceuticals, East Hanover, NJ (R.J., P.Z., B.M., J. Legos); University Hospital Zürich Skin Cancer Center, Zurich, Switzerland (R.D.); and the Melanoma Program, Hillman UPMC Cancer Center, University of Pittsburgh, Pittsburgh (J.M.K.).
Reinhard DummerFrom the Melanoma Institute Australia, University of Sydney, Royal North Shore and Mater Hospitals (G.V.L.), and Macquarie University, Melanoma Institute Australia, University of Sydney, and Westmead Hospital (R.K.), Sydney, Princess Alexandra Hospital, Gallipoli Medical Research Foundation, University of Queensland, Brisbane (V.A.), and Alfred Hospital, Melbourne, VIC (A. Haydon) - all in Australia; University Hospital Schleswig-Holstein, Kiel (A. Hauschild), and University Hospital Essen, Essen, and the German Cancer Consortium, Heidelberg (D.S.) - all in Germany; Fondazione Istituto Nazionale Tumori, Milan (M.S.), Papa Giovanni XXIII Cancer Center Hospital, Bergamo (M.M.), and the Melanoma Oncology Unit, Veneto Oncology Institute, Padua (V.C.-S.) - all in Italy; Rikshospitalet-Radiumhospitalet, Oslo (M.N.); Centre Hospitalier Universitaire de Bordeaux, Hôpital Saint-André, Bordeaux (C.D.), Institute Gustave Roussy, Paris (C.R.), Université de Lille, INSERM Unité 1189, Centre Hospitalier Régional Universitaire de Lille, Lille (L.M.), and the Medical Oncology Department, Centre Eugène Marquis, Rennes (T.L.) - all in France; Ella Institute for Melanoma, Sheba Medical Center, Tel Hashomer, Israel (J.S.); Royal Marsden NHS Foundation Trust, London (J. Larkin), and Northern Centre for Cancer Care, Freeman Hospital, Newcastle upon Tyne (R.P.) - both in the United Kingdom; Novartis Pharmaceuticals, East Hanover, NJ (R.J., P.Z., B.M., J. Legos); University Hospital Zürich Skin Cancer Center, Zurich, Switzerland (R.D.); and the Melanoma Program, Hillman UPMC Cancer Center, University of Pittsburgh, Pittsburgh (J.M.K.).
John M KirkwoodFrom the Melanoma Institute Australia, University of Sydney, Royal North Shore and Mater Hospitals (G.V.L.), and Macquarie University, Melanoma Institute Australia, University of Sydney, and Westmead Hospital (R.K.), Sydney, Princess Alexandra Hospital, Gallipoli Medical Research Foundation, University of Queensland, Brisbane (V.A.), and Alfred Hospital, Melbourne, VIC (A. Haydon) - all in Australia; University Hospital Schleswig-Holstein, Kiel (A. Hauschild), and University Hospital Essen, Essen, and the German Cancer Consortium, Heidelberg (D.S.) - all in Germany; Fondazione Istituto Nazionale Tumori, Milan (M.S.), Papa Giovanni XXIII Cancer Center Hospital, Bergamo (M.M.), and the Melanoma Oncology Unit, Veneto Oncology Institute, Padua (V.C.-S.) - all in Italy; Rikshospitalet-Radiumhospitalet, Oslo (M.N.); Centre Hospitalier Universitaire de Bordeaux, Hôpital Saint-André, Bordeaux (C.D.), Institute Gustave Roussy, Paris (C.R.), Université de Lille, INSERM Unité 1189, Centre Hospitalier Régional Universitaire de Lille, Lille (L.M.), and the Medical Oncology Department, Centre Eugène Marquis, Rennes (T.L.) - all in France; Ella Institute for Melanoma, Sheba Medical Center, Tel Hashomer, Israel (J.S.); Royal Marsden NHS Foundation Trust, London (J. Larkin), and Northern Centre for Cancer Care, Freeman Hospital, Newcastle upon Tyne (R.P.) - both in the United Kingdom; Novartis Pharmaceuticals, East Hanover, NJ (R.J., P.Z., B.M., J. Legos); University Hospital Zürich Skin Cancer Center, Zurich, Switzerland (R.D.); and the Melanoma Program, Hillman UPMC Cancer Center, University of Pittsburgh, Pittsburgh (J.M.K.).
Centre Eugène Marquis · FRCentre Hospitalier Universitaire de Lille · FRDeutschen Konsortium für Translationale Krebsforschung · DEFreeman Hospital · GBHôpital Saint-André · FRInstitut Gustave Roussy · FRMylan (Switzerland) · CHOspedale Papa Giovanni XXIII · ITRoyal Marsden NHS Foundation Trust · GBSheba Medical Center · ILThe Alfred Hospital · AUThe University of Queensland · AUThe University of Sydney · AUUniversity Hospital of Zurich · CHUniversity Hospital Schleswig-Holstein · DEUPMC Hillman Cancer Center · USWestmead Hospital · AU

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundCombination therapy with the BRAF inhibitor dabrafenib plus the MEK inhibitor trametinib improved survival in patients with advanced melanoma with BRAF V600 mutations. We sought to determine whether adjuvant dabrafenib plus trametinib would improve outcomes in patients with resected, stage III melanoma with BRAF V600 mutations.

methodsIn this double-blind, placebo-controlled, phase 3 trial, we randomly assigned 870 patients with completely resected, stage III melanoma with BRAF V600E or V600K mutations to receive oral dabrafenib at a dose of 150 mg twice daily plus trametinib at a dose of 2 mg once daily (combination therapy, 438 patients) or two matched placebo tablets (432 patients) for 12 months. The primary end point was relapse-free survival. Secondary end points included overall survival, distant metastasis-free survival, freedom from relapse, and safety.

resultsAt a median follow-up of 2.8 years, the estimated 3-year rate of relapse-free survival was 58% in the combination-therapy group and 39% in the placebo group (hazard ratio for relapse or death, 0.47; 95% confidence interval [CI], 0.39 to 0.58; P<0.001). The 3-year overall survival rate was 86% in the combination-therapy group and 77% in the placebo group (hazard ratio for death, 0.57; 95% CI, 0.42 to 0.79; P=0.0006), but this level of improvement did not cross the prespecified interim analysis boundary of P=0.000019. Rates of distant metastasis-free survival and freedom from relapse were also higher in the combination-therapy group than in the placebo group. The safety profile of dabrafenib plus trametinib was consistent with that observed with the combination in patients with metastatic melanoma.

conclusionsAdjuvant use of combination therapy with dabrafenib plus trametinib resulted in a significantly lower risk of recurrence in patients with stage III melanoma with BRAF V600E or V600K mutations than the adjuvant use of placebo and was not associated with new toxic effects. (Funded by GlaxoSmithKline and Novartis; COMBI-AD ClinicalTrials.gov, NCT01682083 ; EudraCT number, 2012-001266-15 .).

Indexed as

Adjuvants, ImmunologicAdolescentAdultAgedAged, 80 and overAntineoplastic Combined Chemotherapy ProtocolsCutaneous Malignant MelanomaDouble-Blind MethodFemaleHumansImidazolesMaleMelanomaMiddle AgedMutationNeoplasm Recurrence, LocalAdjuvants, ImmunologicBRAF protein, humandabrafenibImidazolesOximesProto-Oncogene Proteins B-rafPyridonesPyrimidinonestrametinib

Identifiers

PMID28891408
OpenAlexW2752210999

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