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Published on: May 24, 2016
Five-Year Outcomes with Dabrafenib plus Trametinib in Metastatic Melanoma
Caroline Robert1, Jean J Grob1, Daniil Stroyakovskiy1
1From Institut Gustave Roussy and Paris-Sud-Paris-Saclay University, Villejuif (C.R.), Aix-Marseille University, Marseille (J.J.G.), and Assistance Publique-Hôpitaux de Paris Dermatology and Clinical Investigation Center, Unité 976, Université de Paris, Hôpital Saint-Louis, Paris (C.L.) - all in France; Moscow City Oncology Hospital, Moscow (D. Stroyakovskiy), and the Petrov Research Institute of Oncology, St. Petersburg (E.L.) - both in Russia; Przychodnia Lekarska Komed, Konin (B.K.), the University of Medical Sciences, Poznań (A.M.), and the Maria Skłodowska-Curie Institute-Oncology Center, Warsaw (P.R.) - all in Poland; the University Hospital Schleswig-Holstein, Kiel (A.H.), the Department of Dermatology, University of Tübingen, Tübingen (C.G.), University Hospital Essen, Essen (D. Schadendorf), and the German Cancer Consortium, Heidelberg (D. Schadendorf) - all in Germany; the Veneto Institute of Oncology, Padua (V.C.S.), and Papa Giovanni XXIII Hospital, Bergamo (M.M.) - both in Italy; the Ella Lemelbaum Institute for Immuno-Oncology and Melanoma, Sheba Medical Center, Tel Hashomer (J.S.), and Sackler Medical School, Tel Aviv University, Tel Aviv (J.S.) - both in Israel; Dnipropetrovsk State Medical Academy, Dnipropetrovsk, Ukraine (I.B.); Laiko General Hospital, National and Kapodistrian University of Athens School of Medicine, Athens (H.G.); the Netherlands Cancer Institute, Amsterdam (J.B.A.G.H.); Mount Vernon Cancer Centre, Northwood, United Kingdom (P.D.N.); the University of California, Los Angeles, Los Angeles (A.R.); the University of Texas M.D. Anderson Cancer Center, Houston (M.A.D.); Massachusetts General Hospital Cancer Center and Harvard Medical School, Boston (K.T.F.); Novartis Pharma, Basel, Switzerland (P.B.); Novartis Pharmaceuticals, East Hanover, NJ (M.T., E.G., M.V.); and the Melanoma Institute Australia, the University of Sydney, and Royal North Shore and Mater Hospitals, Sydney (G.V.L.).
First-line BRAF inhibitors plus MEK inhibitors provide long-term survival benefits for patients with BRAF V600E/K unresectable or metastatic melanoma. Approximately one-third of patients experienced durable benefit from dabrafenib and trametinib combination therapy.
Area of Science:
- Oncology
- Medical Genetics
Background:
- Metastatic melanoma with BRAF V600E/K mutations often treated with BRAF and MEK inhibitors.
- Long-term outcomes of this combination therapy are not well-defined.
Purpose of the Study:
- To evaluate 5-year survival rates in patients with BRAF V600E/K metastatic melanoma receiving BRAF and MEK inhibitors.
- To identify clinical characteristics associated with durable benefit from combination therapy.
Main Methods:
- Pooled analysis of extended-survival data from two randomized trials (COMBI-d and COMBI-v).
- Patients received dabrafenib plus trametinib as first-line treatment.
- Median follow-up of 22 months, with data extending up to 76 months.
Main Results:
- 5-year progression-free survival rate was 19%; 5-year overall survival rate was 34%.
- Complete response (19% of patients) was associated with a 5-year overall survival rate of 71%.
- Baseline factors like performance status and LDH levels impacted survival.
Conclusions:
- First-line dabrafenib plus trametinib offers long-term benefit for approximately one-third of patients with BRAF V600E/K metastatic melanoma.
- Achieving a complete response is a strong predictor of long-term survival.
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