Five-Year Analysis of Adjuvant Dabrafenib plus Trametinib in Stage III Melanoma

Reinhard Dummer ¹, Axel Hauschild ¹, Mario Santinami ¹

⁰From University Hospital Zurich Skin Cancer Center, Zurich, Switzerland (R.D.); University Hospital Schleswig-Holstein, Kiel (A. Hauschild), University Hospital Essen, Essen (D.S.), and German Cancer Consortium, Heidelberg (D.S.) - all in Germany; Fondazione IRCCS Istituto Nazionale dei Tumori, Milan (M.S.), Papa Giovanni XXIII Cancer Center Hospital, Bergamo (M.M.), and the Melanoma Oncology Unit, Veneto Oncology Institute-IRCCS, Padua (V.C.S.) - all in Italy; Princess Alexandra Hospital, Gallipoli Medical Research Foundation, University of Queensland, Brisbane (V.A.), Alfred Hospital, Melbourne, VIC (A. Haydon), and Melanoma Institute Australia, University of Sydney, and Royal North Shore and Mater Hospitals, Sydney (G.V.L.) - all in Australia; the Melanoma Program, UPMC Hillman Cancer Center, University of Pittsburgh, Pittsburgh (J.M.K.); Royal Marsden NHS Foundation Trust, London (J.L.), and the Northern Centre for Cancer Care, Freeman Hospital and Newcastle University, Newcastle upon Tyne (R.P.) - both in the United Kingdom; Oslo University Hospital, the Norwegian Radium Hospital, Oslo (M.N.); Centre Hospitalier Universitaire de Bordeaux, Hôpital Saint-André, Bordeaux (C.D.), Gustave Roussy and Paris-Sud-Paris-Saclay University, Villejuif (C.R.), Université de Lille, INSERM Unité 1189, Lille (L.M.), and the Medical Oncology Department, Centre Eugène Marquis, Rennes (T.L.) - all in France; Ella Lemelbaum Institute for Immuno-Oncology and Melanoma, Sheba Medical Center, Tel Hashomer, and Sackler School of Medicine, Tel-Aviv University, Tel-Aviv - both in Israel (J.S.); Novartis Healthcare, Hyderabad, India (K.D.); and Novartis Pharmaceuticals, East Hanover, NJ (E.G., M.T.).

The New England Journal of Medicine +

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September 3, 2020

View abstract on PubMed

Summary

Adjuvant dabrafenib plus trametinib significantly improved relapse-free survival in patients with resected stage III melanoma. Five-year follow-up confirmed these benefits without apparent long-term toxic effects.

Area Of Science

Oncology
Dermatology
Pharmacology

Background

Previous analysis showed adjuvant dabrafenib plus trametinib improved relapse-free survival in resected stage III melanoma with BRAF mutations.
Longer-term data were needed to confirm the sustained benefit of this adjuvant therapy.

Purpose Of The Study

To report 5-year results for relapse-free survival and survival without distant metastasis.
To assess the long-term efficacy and safety of adjuvant dabrafenib plus trametinib in melanoma patients.

Main Methods

Phase 3 trial randomized 870 patients with resected stage III melanoma (BRAF V600E/K mutations) to 12 months of dabrafenib/trametinib or placebo.
Primary endpoint was relapse-free survival; secondary endpoints included survival without distant metastasis.
Follow-up extended to a minimum of 59 months (median 60 months).

Main Results

At 5 years, 52% of patients on dabrafenib/trametinib were alive without relapse vs. 36% on placebo (HR 0.51).
Survival without distant metastasis at 5 years was 65% with dabrafenib/trametinib vs. 54% with placebo (HR 0.55).
No clinically meaningful difference in serious adverse events was observed between groups during follow-up.

Conclusions

Adjuvant dabrafenib plus trametinib demonstrated a sustained benefit in prolonging survival without relapse or distant metastasis at 5 years.
The combination therapy showed no apparent long-term toxic effects in patients with resected stage III melanoma.
These findings support dabrafenib plus trametinib as a standard adjuvant treatment for this patient population.