Ongoing trials suggest that the combination of dabrafenib (Tafinlar) and trametinib (Mekinist) may be significantly more effective than dabrafenib monotherapy in patients with BRAF V600E/K mutation-positive metastatic melanoma. However, many patients who would be candidates for this dual therapy may not be receiving it.
“This is clearly the standard of care and has been for some time, although some oncologists to my surprise are still using single agent BRAF inhibitors. The economic question is a difficult one and requires much discussion, but from a pure clinical point of view the combination of BRAF plus MEK drugs is safer, less toxic and clearly more effective than either drug alone,” said Jeffrey Weber, MD, PhD, who is the director of the Donald A. Adam Comprehensive Melanoma Research Center at Moffitt Cancer Center, Tampa, FL.
In January 2014, the U.S. Food and Drug Administration (FDA) granted accelerated approval to trametinib and dabrafenib for use in combination to treat patients with unresectable or metastatic melanoma with a BRAF V600E or V600K mutation as detected by an FDA-approved test.1
In February 2015, the latest data from an ongoing study showed combination therapy resulted in a significant reduction in the risk of disease progression and/or death compared to dabrafenib alone as assessed by investigators.2
The phase 3 randomized, double-blinded study (NCT01584648) included 423 patients with unresectable (stage 3C) or metastatic (stage 4) disease. Patients with BRAF V600E/K mutation-positive cutaneous melanoma were randomly assigned at 14 sites in Australia, Europe, and North and South America.
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Completion of this study is a post-marketing requirement for the FDA’s Accelerated Approval for the combination therapy. The final data from the phase 3 study will be submitted to regulatory authorities for review over the next few months.
Trametinib was approved in 2013 by the FDA as a single agent for treatment of BRAF V600E or V600K mutation-positive unresectable or metastatic melanoma. Dabrafenib also was approved in 2013 as a single agent for treatment of BRAF V600E mutation-positive unresectable or metastatic melanoma.