Dr. Herbst Explores Molecular Testing in Lung Cancer

Roy S. Herbst MD, PhD, Chief of Medical Oncology, Director for Translational Research, Clinical Research Program Leader, Thoracic Oncology Program, Yale Cancer Center, explores the driver mutations and molecular testing techniques that can be utilized to help determine an effective treatment for patients with lung cancer.

Herbst says using a multiplex assay to detect multiple gene aberrations is the future, since biopsy samples are limited. It is important to detect mutations in EGFR and the ALK translocations because these are actionable with either erlotinib or crizotinib. Additionally, the ROS1 translocation is also treatable with crizotinib. These mutations make up approximately 18-20% of all lung cancer patients.

The remaining 80% will have mutations in the PI3-kinase pathway, RAS, and HER2 but all in the order of one or two percent. Multiplexing allows you to detect these at the same time as the actionable driver mutations. If you know the molecular makeup of the patient, you can put them on an applicable clinical trial.

Herbst is an advocate for rebiopsy. Inevitably when you treat a patient with crizotinib or an EGFR inhibitor like erlotinib, they will become refractory because of resistance through certain mechanisms. This may call for a need to rebiopsy, in order to understand why the patient has become resistant and to tailor the next treatment. For instance, it may be useful to understand the role of a T790M mutation in EGFR drug resistance.