SC14.01 Immunotherapy in the First-Line Setting of Advanced NSCLC

Abstract

Lung cancer remains the leading cause of cancer-related deaths worldwide. Advances in screening, surgery and treatment have helped to improve the median survival for patients with lung cancer over the past decade, however, the five-year survival rate remains less than 20%. The majority of patients are diagnosed with advanced stage disease, who are treated with platinum-based chemotherapy, followed by targeted, combination, or immunotherapies. Given the response rates seen with the use of immunotherapy in the second-line setting, it was appropriate to begin to explore if these agents could be given to patients earlier in their treatment. Immunotherapies have been found to be better tolerated than chemotherapy and have the potential for long-term survival, thus could benefit patients as first-line therapy, as some patients will never go on to receive second-line treatment. Two agents, nivolumab and pembrolizumab, both monoclonal antibodies targeting programmed cell death protein 1 (PD-1), are approved for use in patients with non-small cell lung cancer (NSCLC) who have received prior chemotherapy. The KEYNOTE-024 randomized phase III trial of pembrolizumab vs. standard of care (platinum-based chemotherapy), demonstrated superior progression-free survival (PFS) and overall survival (OS) for first-line treatment in patients with tumors expressing high levels of programmed cell death ligand 1 (PD-L1) (tumor proportion score ≥50%). The CheckMate-026 randomized, phase III study of nivolumab vs. standard of care in treatment-naïve patients with tumors expressing ≥5% PD-L1 did not meet the primary endpoint of PFS. For this presentation, the use of predictive markers in the front-line setting will be discussed and implications for combination therapy will be reviewed. NSCLC, PD-L1, Immunotherapy