Genetic variants as predictors of toxicity and response in patients with non-small cell lung cancer undergoing first-line platinum-based chemotherapy: Design of the multicenter PGxLUNG study.

Introduction Platinum-based chemotherapy is currently the most frequently applied first-line treatment for patients with advanced non-small cell lung cancer (NSCLC) without targetable mutations or high PD-L1 expression. Unfortunately, chemotherapy-induced toxicity is prevalent and may affect patients' quality of life to a considerable extent. Presumably, genetic variants of genes, coding for proteins involved in the processes of the development of toxicity, may be of interest as predictors of benefits and harms of platinum-based chemotherapy. The primary objective of the study is to investigate the influence of genetic variants on the incidence of chemotherapy-induced toxicity in patients with NSCLC undergoing first-line platinum-based chemotherapy. The main secondary objectives are to study the association between genetic variants and treatment response and to study the association between skeletal muscle mass (SMM) as well as patient-reported health-related quality of life (HRQOL) and treatment response and toxicity. Methods In this multicenter prospective follow-up study, a total of 350 patients with NSCLC (stage II-IV) undergoing first-line platinum-based chemotherapy will be included. Blood samples for DNA isolation and genotyping, questionnaires and data on patients risk factors and disease stage will be recorded. The primary endpoint is chemotherapy-induced (non-)hematological toxicity, comprising; nephrotoxicity, neuropathy, esophagitis, ototoxicity, pneumonitis, gastrointestinal toxicity, anemia, leukocytopenia, neutropenia and thrombocytopenia. Secondary endpoints include dose-limiting toxicity, HRQOL, and treatment response (radiological response [RECIST 1.1] and overall survival [OS]). Discussion Results of the PGxLUNG study will be primarily used to determine the influence of genetic variants on the incidence of chemotherapy-induced toxicity in patients with NSCLC undergoing first-line platinum-based chemotherapy.