Evolving treatments and prognosis in Stage IV non-small cell lung cancer: 20 years of progress of novel therapies.

Abstract

BACKGROUND: Advancements in pharmacotherapy, including molecular targeted therapies and immune checkpoint inhibitors, have revolutionized the treatment for Stage IV non-small cell lung cancer (NSCLC) over the past two decades. However, differences in drug approval timelines across countries raise important questions about their impact on survival rates. This study investigates trends in overall survival (OS), patient characteristics, and the association between OS improvements and the introduction of new drugs. PATIENTS AND METHODS: This retrospective review included patients with Stage IV NSCLC treated at the National Cancer Center Hospital in Japan from 2001 to 2021. Using data from the Department of Thoracic Oncology registries, 2,555 patients were identified and categorized into four time periods: 2001-2005 (Group A), 2006-2010 (Group B), 2011-2015 (Group C), and 2016-2021 (Group D). RESULTS: While baseline characteristics remained relatively consistent, Group D had an increased proportion of elderly patients (≥ 75 years) and those with brain metastases. Additionally, the gender ratio became more balanced over time. Notably, Group D patients with EGFR mutations or ALK fusion positivity and older age demonstrated significantly longer OS. Analysis revealed steady and substantial improvements in OS across time periods (median OS: Group A, 10.68 months; Group B, 14.12 months; Group C, 16.49 months; and Group D, 25.46 months, respectively). CONCLUSIONS: This study demonstrates marked improvements in survival for patients with Stage IV NSCLC, particularly in the last six years, despite the increase in brain metastases and elderly patients. This finding suggests the crucial role of novel therapies in enhancing survival outcomes.