PL 03.04 Current Status and Future of Immunotherapy in Lung Cancer

Abstract

The therapeutic approach to overcome Tumor-induced suppression of specific T-cell activation by using specific antibodies, which are interacting with regulating pathways, the immune check-points has substantially changed treatment of patients with advanced NSCLC. In particular the development of antibodies inhibiting cytotoxic T-lymphocyte-associated antigen 4 (anti CTL4), programmed death receptor 1 (anti PD-1) or programmed death receptor ligand 1 (anti PDL-1) have shown efficacy in NSCLC. In five randomized trials anti PD-1/anti PD-L1 antibodies have shown significant improvement in overall survival (OS) compared to chemotherapy and an improved safety profile. Efficacy was correlated to PD-L1 expression on tumor cells. However confirmed activity has also been documented in patients with PD-L1 negative tumors. Besides harmonization of different existing tests for assessment of PD-L1 expression identification of novel markers like tumor mutational burden (TMB) might help to identify best benefitting patients. In selected patients with high PD-L1 expression on tumor cells (TPS =/> 50%) monotherapy with the anti PD1 antibody pembrolizumab has demonstrated superiority in response, progression free survival and OS compared to platinum based chemotherapy in first-line treatment. Current randomized trials evaluate the activity of combinations of chemotherapy with checkpoint inhibitors or of immunotherapy combinations compared to chemotherapy and will provide important information about the next steps in the development of immunotherapy in lung cancer. For the future the development of novel immunotherapeutic agents either as monotherapy or in combination with checkpoint inhibitors as well as the understanding of resistance mechanisms and strategies to overcome resistance will be of paramount importance.