2021 Health Equity and Inclusiveness Junior Investigator Award Melina Marmarelis, MD The University of Pennsylvania Philadelphia PA Research Summary Detection of genetic changes in lung tumors has improved our understanding of what drives lung cancer to grow. Importantly, highly effective anti-cancer pills have been developed to target tumor genetic changes in genes such as EGFR, ALK or ROS1. Patients with targetable genetic changes live longer if they are able to receive a targeted pill-based therapy compared to conventional lung cancer treatments. It is therefore imperative that we find these targetable genetic changes when they exist. Previous studies have shown that targetable genetic changes in lung tumors are more common in women, never smokers, younger adults, and people of Asian descent. Because of this association, patients without these characteristics do not always have their tumor tested to find these genetic changes. This project will look at over 2000 patients with targetable genetic changes in EGFR, ALK or ROS1 and investigate whether patient characteristics not usually associated with detection of a targetable genetic change (e.g. male gender, age >65, smoking history, African American, Hispanic) are associated with delayed detection of a target and delayed receipt of the targeted therapy. In addition, we will look at the effect of delayed receipt of targeted therapy on survival and frequency of cancer spreading to the brain. We hypothesize that delayed receipt of targeted therapy could lead to shorter survival and a higher incidence of spread to the brain. These findings will help us develop interventions to improve detection of these targets and delivery of targeted therapy for all lung cancer patients. Technical Abstract Background: Patients with NSCLC whose tumors harbor a targetable molecular alteration have improved outcomes when they receive targeted therapy. Historically, targetable alterations have been associated with specific patient characteristics such as female gender, young age, non-smokers, and Asians. Given this association, patients with characteristics not commonly associated with targetable mutations do not always receive timely and complete molecular testing. We hypothesize that male gender, age >65, history of smoking, African American race and Hispanic ethnicity will be independently associated with delayed detection and treatment of a targetable alteration. We will evaluate the impact of delayed targeted therapy on overall survival and brain metastasis development. Methods: We will perform a retrospective cohort study of approximately 2200 patients with EGFR, ALK or ROS1 targetable alterations obtained through multi-institution retrospective chart review. Multivariate logistic regression will be used to evaluate the association of patient characteristics with complete molecular testing prior to first-line therapy, targeted therapy as first-line therapy, and development of brain metastases. Kaplan-Meier methodology will be used to estimate median overall survival. The log rank test will be used to compare median overall survivals. Multivariate Cox Regression will further evaluate interactions between delayed targeted therapy and patient characteristics as well as help control for potential confounders. Importance: This will be the first study to evaluate the impact of delayed detection and delayed treatment of driver mutations in NSCLC. This information is critical to designing interventions to improve outcomes in patient groups with characteristics not usually associated with driver mutations.
