Overall survival and durable responses in patients with BRAF V600-mutant metastatic melanoma receiving dabrafenib combined with trametinib

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, Gerald S. Falchook, Alain Algazi, Karl Lewis, Igor Puzanov, Nageatte Ibrahim, Peng SunElizabeth Cunningham, Amy S. Kline, Heather Del Buono, Diane Opatt McDowell, Kiran Patel, Keith T. Flaherty

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

166 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)871-878
Number of pages8
JournalJournal of Clinical Oncology
Volume34
Issue number8
DOIs
Publication statusPublished - 10 Mar 2016

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