Overall Survival and Durable Responses in Patients With BRAF V600-Mutant Metastatic Melanoma Receiving Dabrafenib Combined With Trametinib.

Abstract

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.

• Authors: Georgina V Long, Jeffrey S Weber, Jeffrey R Infante, Kevin B Kim, Adil Daud, Rene Gonzalez, Jeffrey A Sosman, Omid Hamid, Lynn Schuchter, Jonathan Cebon, Richard F Kefford, Donald Lawrence, Ragini Kudchadkar, Howard A Burris 3rd, Gerald S Falchook, Alain Algazi, Karl Lewis, Igor Puzanov, Nageatte Ibrahim, Peng Sun, Elizabeth Cunningham, Amy S Kline, Heather Del Buono, Diane Opatt McDowell, Kiran Patel, Keith T Flaherty
• Journal: Journal of clinical oncology : official journal of the American Society of Clinical Oncology (J Clin Oncol) Vol. 34 Issue 8 Pg. 871-8 (Mar 10 2016) ISSN: 1527-7755 [Electronic] United States
• PMID: 26811525 (Publication Type: Clinical Trial, Phase I, Clinical Trial, Phase II, Journal Article, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)
• Copyright: © 2016 by American Society of Clinical Oncology.

Chemical References

• Imidazoles
• Oximes
• Pyridones
• Pyrimidinones
• trametinib
• BRAF protein, human
• Proto-Oncogene Proteins B-raf
• dabrafenib

Topics

• Adult
• Aged
• Antineoplastic Combined Chemotherapy Protocols (therapeutic use)
• Female
• Humans
• Imidazoles (administration & dosage)
• Male
• Melanoma (drug therapy, enzymology, genetics, pathology)
• Middle Aged
• Mutation
• Neoplasm Metastasis
• Oximes (administration & dosage)
• Proto-Oncogene Proteins B-raf (genetics)
• Pyridones (administration & dosage)
• Pyrimidinones (administration & dosage)
• Survival Rate