• The combination of dabrafenib and trametinib shows early antitumor activity (ORR of 63%).
• Adverse events were manageable.

An important “basket” in oncology relates to BRAF tumor mutations, specifically V600E activating mutations. In melanoma, BRAF inhibitors alone or in combination with MEK inhibitors have resulted in robust responses, but the same is not yet true in colorectal cancer. A previous report in NSCLC demonstrated that the BRAF inhibitor dabrafenib resulted in a 32% response rate in patients with BRAF V600E mutations, and at ASCO 2015 data were presented on dabrafenib and trametinib — the same combination that is now approved for unresectable or metastatic BRAF V600E or BRAF V600K mutation-positive melanoma — in 24 patients, with a response rate of 63%. In melanoma, the side-effect profile of the combined BRAF/MEK inhibitor regimen is similar to that reported with single agents, but differences have been observed. In this Phase II study, 9 out of 33 patients (27%) experienced adverse events leading to dose modification. These new data suggest that NSCLC may follow a similar research pathway to melanoma, meaning that these combinations may eventually be considered up front.