Trends in lung cancer mortality among U.S. adults aged ≥55 before and after the introduction of immunotherapy: A CDC WONDER Joinpoint-style analysis.

Abstract

8595 Background: Lung cancer remains the leading cause of cancer-related mortality in the United States. Although sustained reductions in tobacco use have contributed to gradual declines in incidence and mortality, recent therapeutic advances have transformed the management of non–small cell lung cancer. The introduction of immune checkpoint inhibitors (ICIs) in the early 2010s led to substantial survival gains in clinical trials and shifted treatment paradigms toward frontline and perioperative settings. Whether these advances have translated into accelerated reductions in lung cancer mortality at the population level remains incompletely characterized. Methods: We conducted a nationwide population-based analysis using the CDC WONDER Underlying Cause of Death database from 1999 to 2020. Lung cancer deaths were identified using ICD-10 codes C34.0–C34.9. Annual age-adjusted mortality rates per 100,000 population standardized to the 2000 U.S. population were analyzed. Among adults aged ≥55 years, joinpoint-style segmented log-linear regression was used to identify inflection points and estimate annual percent changes (APC) before and after the identified breakpoint. Results: From 1999 to 2020, age-adjusted lung cancer mortality declined substantially. Among adults aged ≥55 years, segmented regression identified a significant inflection point in 2011. Prior to 2011, mortality declined at −1.52% per year, whereas after 2011 the decline accelerated to −3.88% per year (p < 0.001 for change in slope). In the overall population, mortality declined from 55.4 to 48.8 per 100,000 between 1999 and 2014 (APC −0.7%/year) and decreased more rapidly from 47.8 to 41.3 per 100,000 between 2015 and 2020 (APC −2.9%/year), representing more than a fourfold acceleration. Conclusions: In this nationwide age-adjusted analysis, lung cancer mortality demonstrated a sustained decline over two decades, with a marked acceleration beginning in the early 2010s. Although reductions in tobacco use remain an important contributor, the timing and magnitude of this acceleration, particularly among adults aged ≥55 years, are consistent with population-level benefits associated with advances in systemic therapy, including immune checkpoint inhibitors. These findings suggest that rapid clinical adoption of immunotherapy may have contributed to meaningful real-world improvements in lung cancer mortality. Age-adjusted U.S. lung cancer mortality before and after immunotherapy integration, 1999–2020. Era Years Start rate End rate Percent decline APC (% per year) Pre-immunotherapy 1999-2014 55.4 48.8 -10.5% -0.7 Immunotherapy era 2015-2020 47.8 47.8 -13.6% -2.9 APC = annual percent change. Rates are age-adjusted to the 2000 U.S. standard population.