Dr. Subbiah on the FDA Approval of Dabrafenib/Trametinib in BRAF V600E–Mutated Solid Tumors

Vivek Subbiah, MD, an associate professor in the Investigational Cancer Therapeutics Department and the Center Clinical Medical Director of the Clinical Center for Targeted Therapy, Cancer Medicine Division, at The University of Texas MD Anderson Cancer Center, discusses the FDA approval of dabrafenib (Tafinlar) plus trametinib (Mekinist) for the treatment of patients with BRAF V600E–mutated unresectable or metastatic solid tumors.

In June 2022, the FDA approved the combination for the treatment of adult and pediatric patients aged 6 years and older with unresectable or metastatic solid tumors harboring BRAF V600E mutations who have progressed following previous treatment and who have no satisfactory alternative treatment options. In the phase 2 ROAR basket study (NCT02034110) and arm H of the NCI-MATCH study (NCT02465060), the doublet produced overall response rates of up to 80% in patients with BRAF V600E–mutated solid tumors, including high- and low-grade glioma, biliary tract cancer and select gynecological and gastrointestinal cancers.

Previously, agents were approved for the treatment of patients with melanoma harboring BRAF mutations, and studies were then conducted across multiple solid tumor types that had a provenance for BRAF V600E mutations, Subbiah notes. However, patients with BRAF V600E–mutated colorectal cancer (CRC) did not respond to BRAF-targeted agents. Subsequently, CRC was found to be an exception for BRAF inhibition due to EGFR creating a mechanism of resistance. As such, treatment for patients with BRAF V600E–mutated CRC required the addition of an EGFR inhibitor, Subbiah adds.

Despite the resistance in CRC, BRAF inhibitors, when combined with a MET inhibitor, were found to be active across cancer types harboring BRAF V600E mutations, Subbiah continues. The combination of dabrafenib and trametinib is a testament to how precision medicine can help shape new treatments spanning different cancer types, Subbiah concludes.