Abstract
BackgroundSignificant improvements in mortality among patients with non-small cell lung cancer (NSCLC) in the USA over the past two decades have been reported based on Surveillance, Epidemiology, and End Results (SEER) data. The timing of these improvements led to suggestions that they result from the introduction of new treatments; however, few studies have directly investigated this. The aim of this study was to investigate the extent to which population level improvements in survival of advanced and/or metastatic NSCLC (admNSCLC) patients were associated with changes in treatment patterns.MethodsWe utilized a de-identified database to select three cohorts of patients with admNSCLC: (1) patients with non-oncogene (EGFR/ALK/ROS1/BRAF) positive tumors, (2) patients with ALK-positive (ALK+) tumors, and (3) patients with EGFR-positive (EGFR+) tumors. All patients were diagnosed with admNSCLC between 2012 and 2019. Multivariable Cox models adjusting for baseline characteristics and receipt of targeted and immunotherapy were utilized to explore the relationship between these variables and changes in the hazard of death by calendar year in each cohort.ResultsWe included 28,154 admNSCLC patients with non-oncogene positive tumors, 598 with ALK+ tumors, and 2464 with EGFR+ tumors eligible for analysis. After adjustment for differences in baseline characteristics, the hazard of death in patients who had non-oncogene positive tumors diagnosed in 2015, 2016, 2017, 2018 ,and 2019 was observed to be 12%, 11%, 17%, 20%, and 21% lower respectively than that for those diagnosed in 2012. Upon additionally adjusting for receipt of first line or second line immunotherapy, the decrease in the hazard of death by calendar year was no longer observed, suggesting improvements in survival observed over time may be explained by the introduction of these treatments. Similarly, decreases in the hazard of death were only observed in patients with ALK+ tumors diagnosed between 2017 and 2019 relative to 2012 but were no longer observed following adjustment for the use of 1st and later generation ALK inhibitors. Among patients with EGFR+ tumors, the hazard of death did not improve significantly over time.ConclusionOur findings expand on the SEER data and provide additional evidence suggesting improvements in survival of patients with advanced and metastatic NSCLC over the past decade could be explained by the change in treatment patterns over this period.
Highlights
Significant improvements in mortality among patients with non-small cell lung cancer (NSCLC) in the USA over the past two decades have been reported based on Surveillance, Epidemiology, and End Results (SEER) data
Our findings expand on the SEER data and provide additional evidence suggesting improvements in survival of patients with advanced and metastatic NSCLC over the past decade could be explained by the change in treatment patterns over this period
The hazard of death adjusting for baseline characteristics in non-oncogene positive patients diagnosed in 2015, 2016, 2017, 2018, and 2019 was observed to be 12%, 11%, 17%, 20%, and 21% lower respectively than that in those diagnosed in 2012 (Fig. 1A)
Summary
Significant improvements in mortality among patients with non-small cell lung cancer (NSCLC) in the USA over the past two decades have been reported based on Surveillance, Epidemiology, and End Results (SEER) data The timing of these improvements led to suggestions that they result from the introduction of new treatments; few studies have directly investigated this. Immunotherapies have emerged as an efficacious treatment option in individuals with tumors not testing positive for these driver oncogenes or among those with tumors testing positive for other biomarkers such as PD-L1 [2, 3] The benefits of these innovative treatments in patients with NSCLC have been demonstrated in clinical trials and observational studies, and they have been proposed as a potentially plausible explanation for the improvements in population level mortality among patients with NSCL C in the USA [4]. In this study, we sought to utilize patient level data from a large US electronic health record (EHR) database to investigate improvements in survival of patients with advanced and/or metastatic NSCLC (admNSCLC) over time and explored their relationship with changes in treatment patterns
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