Clinical Outcomes of First-line Therapies for Advanced Non-Small Cell Lung Cancer

Objectives:To analyze the evolution of clinical outcomes derived from clinical trials on first-line therapies for advanced or metastatic non-small cell lung cancer (NSCLC) published between 2010 and 2020, focusing on how these outcomes impact survival rates and management of patients.Methods:A systematic review of phase III and pivotal phase II clinical trials was conducted by a structured search on Medline and Embase. A comprehensive set of variables was collected to assess their influence on survival rates. We also estimated the clinical benefit by applying the ESMO-MCBS v1.1 and extracted the authors' conclusions.Results:Sixty-six studies involving 34,951 patients were included. Best survival outcomes were found for nonsquamous non-small cell lung cancer (OS and progression-free survival medians: 19.4 and 10.2 mo) and for those expressing molecular targets (OS and progression-free survival medians: 23.8 and 11.0 mo). No significant influence on survival rates was observed for industry funding and disease stage (IIIB/IV vs. IV). ESMO-MCBS v1.1 was applied in 45 positive studies and resulted in a meaningful clinical benefit score in 37.8%. Quality of life (QoL) was reported in 57.6% of the original publications and showed statistical significance favoring the experimental arm in 33.3%. Positive authors' conclusions (75.7% of trials) were based on OS and/or QoL in 34% and on surrogate endpoints in 66%.Conclusions:Extended survival times and a steady improvement in QoL have been observed. However, there were more than twice as many studies reporting positive authors' conclusions as studies meeting the ESMO threshold for meaningful clinical benefit.