In clinical trials, dabrafenib plus trametinib improved overall survival (OS) compared with single-agent BRAF inhibitors (BRAFi) in patients with BRAF V600-mutant unresectable or metastatic melanoma. We investigated dabrafenib plus trametinib therapy in a compassionate-use setting [Named Patient Program (NPP); DESCRIBE II]. A retrospective chart review of patients with BRAF V600-mutated unresectable stage III/IV melanoma receiving dabrafenib plus trametinib as compassionate use was conducted. Treatment patterns and duration, clinical outcomes, and tolerability were evaluated. Of 271 patients, 92.6% had stage IV melanoma, including 36.5% with brain metastases. Overall, 162 patients (59.8%) were BRAFi naive and 171 (63.1%) received first-line dabrafenib plus trametinib. Among BRAFi-naive patients, the overall response rate (ORR) was 67.3%, median OS (mOS) was 20.0 months, and median progression-free survival (mPFS) was 7.5 months. In BRAFi-naive patients with known brain metastases (n = 62), ORR was 61.3%, mOS was 15.5 months, and mPFS was 6.2 months. Eighty-four patients received BRAFi monotherapy for >30 days and switched to dabrafenib plus trametinib prior to progression. Of these 84 patients, 63 had known disease status at the time of switch, and 22 improved with the combination therapy. No new safety signals were identified, and dabrafenib plus trametinib was well tolerated. Dabrafenib plus trametinib showed substantial clinical activity in NPP patients with BRAF V600-mutated unresectable or metastatic melanoma. Analysis of treatment patterns demonstrated the effectiveness of the combination in patients with brain metastases and across lines of therapy with a well tolerated and manageable safety profile.

4 Oncology Division Istituto Dermopatico dell'Immacolata IDI IRCCS Division of Cancer Services Roma Italy

Canberra Hospital Garran ACT Australia

Department of Comprehensive Cancer Care Masaryk Memorial Cancer Institute and Faculty of Medicine Masaryk University Brno Czech Republic

Department of Medical Oncology Melanoma Institute Australia The University of Sydney and Royal North Shore and Mater Hospitals Sydney NSW Australia

Department of Medical Oncology Netherlands Cancer Institute Antoni van Leeuwenhoek Hospital Amsterdam The Netherlands

Department of Medical Oncology University Medical Center Groningen University of Groningen Groningen The Netherlands

Department of Oncology Candiolo Cancer Center University of Torino Torino

Department of Oncology Klaipeda University Hospital Klaipeda Lithuania

Department of Oncology Peter MacCallum Cancer Centre Melbourne VIC Australia

Division of Cancer Services Gallipoli Medical Research Foundation The University of Queensland and Princess Alexandra Hospital Brisbane QLD

Medical Oncology IVO Servicio de Oncología Valencia Spain

Medical Oncology Service Hospital Universitario Insular de Gran Canaria Las Palmas de Gran Canaria Spain

Novartis Pharma AG Basel Switzerland

Oncology Chemotherapy Department Clinic of Internal Medicine Oncology and Family Medicine Vilnius University Vilnius Lithuania

Tumor Biotherapy Unit European Institute of Oncology IRCCS Milano Italy

United BioSource Corporation An Express Scripts Company London UK

United BioSource Corporation An Express Scripts Company Montreal QC Canada

See more in PubMed

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Tafinlar (dabrafenib) [package insert]. 2018, East Hanover, NJ: Novartis Pharmaceuticals Corp

Mekinist (trametinib) [package insert]. 2018, East Hanover, NJ: Novartis Pharmaceuticals Corp

A Retrospective Analysis of Dabrafenib and/or Dabrafenib Plus Trametinib Combination in Patients with Metastatic Melanoma to Characterize Patients with Long-Term Benefit in the Individual Patient Program (DESCRIBE III)