Dr. Pecot on Addressing Mechanisms of Resistance With New Targeted Therapies in NSCLC

Chad V. Pecot, MD, associate professor of oncology, Department of Medicine, University of North Carolina Lineberger Comprehensive Cancer Center, discusses addressing mechanisms of resistance with new targeted therapies in non–small cell lung cancer.

Repotrectinib is an agent that is under development that may represent a more potent inhibitor of ALK and ROS1 mutations compared with other available agents in the paradigm, according to Pecot. ALK and ROS1 are fusion events. When a patient has a lung cancer that is driven by these mutations, the translocation creates a chimeric protein based on their fusion partner, Pecot explains. 

Tumors that harbor these mutations can create mechanisms of resistance, sometimes referred to as “gatekeeper” or “hot spot” mutations, that can reject potent drugs like alectinib (Alecensa), erlotinib (Tarceva), and brigatinib (Alunbrig) rendering them inactive, Pecot adds. As such, newer agents such as repotrectinib and cabozantinib (Cabometyx) are being evaluated to address these mutations and overcome these mechanisms of resistance, Pecot concludes.