A Targeted Therapy Combination for Solid Tumors 

The FDA approved a combination of two kinase inhibitors for the treatment of solid tumors bearing the BRAF V600E mutation. 

The U.S. Food and Drug Administration (FDA) has granted accelerated approval to the kinase inhibitor dabrafenib (Tafinlar), to be used in combination with the kinase inhibitor trametinib (Mekinist), for the treatment of certain patients with solid tumors other than colorectal cancer. Dabrafenib plus trametinib is indicated for patients 6 years of age and older whose tumors have the BRAF V600E mutation. 

Dabrafenib is a type of targeted therapy called a kinase inhibitor. It inhibits the protein BRAF, which, when mutated, can drive tumor formation and progression. Trametinib is also a kinase inhibitor. It inhibits the protein MEK, which is turned on by BRAF. By blocking both MEK and BRAF, the combination can more effectively shut down the oncogenic signaling pathway and potentially delay resistance. 

The approval is based on the combined results of several open-label, multiple cohort clinical trials comprising 131 adult patients and 36 pediatric patients with various solid tumors harboring mutations in BRAF. The objective response rate was 41 percent for adults and 25 percent for pediatric patients. Among adults, the tumor type with the highest response rate was biliary tract cancer, with a response rate of 46 percent. 

Solid tumors are tumors that occur in tissues other than the blood. Examples include melanoma, lung cancer, and thyroid cancer, for which dabrafenib plus trametinib was already approved. Solid tumors account for the vast majority of cancer cases in the U.S. 

The FDA rendered its decision on June 22, 2022. Accelerated approval means that continued approval may be contingent upon confirmatory trials.