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Please use this identifier to cite or link to this item: http://hdl.handle.net/1959.14/1111837
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- Title
- Combined BRAF (Dabrafenib) and MEK inhibition (Trametinib) in patients with BRAFV600-mutant melanoma experiencing progression with single-agent BRAF inhibitor
- Related
- Journal of clinical oncology, Vol. 32, Issue 33, (2014), p.3697-3704
- DOI
- 10.1200/JCO.2014.57.3535
- Publisher
- American Society of Clinical Oncology
- Date
- 2014
- Author/Creator
- Johnson, Douglas B
- Author/Creator
- Flaherty, Keith T
- Author/Creator
- McWilliams, Robert R
- Author/Creator
- Sznol, Mario
- Author/Creator
- Lawrence, Donald P
- Author/Creator
- Gibney, Geoffrey T
- Author/Creator
- Burris III, Howard A
- Author/Creator
- Falchook, Gerald S
- Author/Creator
- Algazi, Alain
- Author/Creator
- Lewis, Karl
- Author/Creator
- Long, Georgina V
- Author/Creator
- Patel, Kiran
- Author/Creator
- Weber, Jeffrey S
- Author/Creator
- Ibrahim, Nageatte
- Author/Creator
- Sun, Peng
- Author/Creator
- Little, Shonda
- Author/Creator
- Cunningham, Elizabeth
- Author/Creator
- Sosman, Jeffrey A
- Author/Creator
- Daud, Adil
- Author/Creator
- Gonzalez, Rene
- Author/Creator
- Infante, Jeffrey R
- Author/Creator
- Kim, Kevin B
- Author/Creator
- Kefford, Richard F
- Author/Creator
- Hamid, Omid
- Author/Creator
- Schuchter, Lynn
- Author/Creator
- Cebon, Jomathan
- Author/Creator
- Sharfman, William H
- Description
- Preclinical and early clinical studies have demonstrated that initial therapy with combined BRAF and MEK inhibition is more effective in BRAF(V600)-mutant melanoma than single-agent BRAF inhibitors. This study assessed the safety and efficacy of dabrafenib and trametinib in patients who had received prior BRAF inhibitor treatment.In this open-label phase I/II study, we evaluated the pharmacology, safety, and efficacy of dabrafenib and trametinib. Here, we report patients treated with combination therapy after disease progression with BRAF inhibitor treatment administered before study enrollment (part B; n = 26) or after cross-over at progression with dabrafenib monotherapy (part C; n = 45).In parts B and C, confirmed objective response rates (ORR) were 15% (95% CI, 4% to 35%) and 13% (95% CI, 5% to 27%), respectively; an additional 50% and 44% experienced stable disease ≥ 8 weeks, respectively. In part C, median progression-free survival (PFS) was 3.6 months (95% CI, 2 to 4), and median overall survival was 11.8 months (95% CI, 8 to 25) from cross-over. Patients who previously received dabrafenib ≥ 6 months had superior outcomes with the combination compared with those treated < 6 months; median PFS was 3.9 (95% CI, 3 to 7) versus 1.8 months (95% CI, 2 to 4; hazard ratio, 0.49; P = .02), and ORR was 26% (95% CI, 10% to 48%) versus 0% (95% CI, 0% to 15%).Dabrafenib plus trametinib has modest clinical efficacy in patients with BRAF inhibitor-resistant melanoma. This regimen may be a therapeutic strategy for patients who previously benefited from BRAF inhibitor monotherapy ≥ 6 months but demonstrates minimal efficacy after rapid progression with BRAF inhibitor therapy.
- Description
- 8 page(s)
- Resource Type
- journal article
- Organisation
- Macquarie University. Department of Clinical Medicine
- Identifier
- http://hdl.handle.net/1959.14/1111837
- Identifier
- mq:50171
- Identifier
- ISSN:0732-183X
- Identifier
- mq-rm-2014004264
- Identifier
- mq_res-se-548445
- Language
- eng
- Reviewed
Macquarie University ResearchOnline
