Overall Survival and Durable Responses in Patients With BRAF V600-Mutant Metastatic Melanoma Receiving Dabrafenib Combined With Trametinib
| Autor: | Karl D. Lewis, Nageatte Ibrahim, Igor Puzanov, Kevin B. Kim, Georgina V. Long, D.P. Lawrence, Omid Hamid, Adil Daud, Elizabeth Cunningham, Gerald Steven Falchook, Howard A. Burris, Keith T. Flaherty, Alain Algazi, Lynn M. Schuchter, Jonathan Cebon, Heather Lynn Del Buono, Amy S. Kline, Jeffrey R. Infante, Kiran Patel, Jeffrey S. Weber, Ragini Kudchadkar, Rene Gonzalez, Diane Opatt McDowell, Richard F. Kefford, Peng Sun, Jeffrey A. Sosman |
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| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Adult Male Proto-Oncogene Proteins B-raf Cancer Research medicine.medical_specialty Metastatic melanoma Pyridones Pyrimidinones Gastroenterology 03 medical and health sciences 0302 clinical medicine Internal medicine Antineoplastic Combined Chemotherapy Protocols Oximes medicine Overall survival Humans In patient Neoplasm Metastasis Survival rate Melanoma Aged Trametinib Errata Trametinib 2 MG business.industry Imidazoles Dabrafenib Middle Aged medicine.disease Surgery Survival Rate 030104 developmental biology Oncology 030220 oncology & carcinogenesis Mutation Female business medicine.drug |
| Zdroj: | Journal of clinical oncology : official journal of the American Society of Clinical Oncology. 34(8) |
| ISSN: | 1527-7755 |
| Popis: | Purpose To report the overall survival (OS) and clinical characteristics of BRAF inhibitor–naive long-term responders and survivors treated with dabrafenib plus trametinib in a phase I and II study of patients with BRAF V600 mutation–positive metastatic melanoma. Methods BRAF inhibitor–naive patients treated with dabrafenib 150 mg twice daily plus trametinib 2 mg daily (the 150/2 group) from the non–randomly assigned (part B) and randomly assigned (part C) cohorts of the study were analyzed for progression-free and OS separately. Baseline characteristics and factors on treatment were analyzed for associations with durable responses and OS. Results For BRAF inhibitor–naive patients in the 150/2 groups (n = 78), the progression-free survival at 1, 2, and 3 years was 44%, 22%, and 18%, respectively, for part B (n = 24) and 41%, 25%, and 21%, respectively, for part C (n = 54). Median OS was 27.4 months in part B and 25 months in part C. OS at 1, 2, and 3 years was 72%, 60%, and 47%, respectively, for part B and 80%, 51%, and 38%, respectively, for part C. Prolonged survival was associated with metastases in fewer than three organ sites and lower baseline lactate dehydrogenase. OS at 3 years was 62% in patients with normal baseline lactate dehydrogenase and 63% in patients with a complete response. Conclusion Dabrafenib plus trametinib results in a median OS of more than 2 years in BRAF inhibitor–naive patients with BRAF V600 mutation–positive metastatic melanoma, and approximately 20% were progression free at 3 years. Durable responses occurred in patients with good prognostic features at baseline, which may be predictive. |
| Databáze: | OpenAIRE |
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