Current status of combination therapies

BRAF targets in melanoma. Biological mechanisms, resistance, and drug discovery. Cancer drug discovery and development. Volume 82. Ed. Ryan J. Sullivan. Springer (2015)


The combination of dabrafenib and trametinib has advanced through the developmental pipeline and received regulatory approval in January 2014. We strongly consider this combination for patients as first-line treatment or following progression with an immune-based regimen. Clinical trials are also ongoing for vemurafenib plus the MEK inhibitor cobimetinib (GDC-0973, Roche/Genentech) and encorafenib plus binimetinib.

A large variety of trials assessing other combinations in the BRAF inhibitor naпve and refractory populations are also ongoing. These include BRAF inhibitors plus agents inhibiting one of the following: the PI3K-AKT pathway, colony-stimulating factor-1 receptor (CSF-1R), cyclin dependant kinase signaling (CDK4/6), heat-shock protein-90 (HSP90), hepatocyte growth factor, fibroblast growth factor receptor (FGFR) and angiogenesis. Table 4.1 is a non-comprehensive list of currently accruing trials combining BRAF inhibitors with other agents [37]. Although each combination has pre-clinical rationale, it is not clear whether one combination will emerge as clearly superior. Likely, a personalized approach will be needed and will be assessed in a planned trial (LOGIC 2, Novartis).

Table 4.1. Currently accruing combination therapy trials including BRAF inhibitors as of January 27, 2014

BRAF Targets in Melanoma_ Biological Mechanisms, Resistance, and Drug Discovery-Springer-Verlag New York (2015) T 4.1

BRAF Targets in Melanoma_ Biological Mechanisms, Resistance, and Drug Discovery-Springer-Verlag New York (2015) T 4.1-2

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