Background: Significant improvements in mortality among NSCLC cancer patients in the US over the past two decades have recently been reported based on SEER data. The timing of these improvements led to suggestions that they are primarily a result of the introduction of new and innovative treatments, however few studies have directly investigated this. Methods: We utilised the US Flatiron Health database to identify a cohort of non-biomarker (EGFR/ALK/ROS1/BRAF) positive metastatic NSCLC (mNSCLC) patients and a separate cohort of ALK positive (ALK+) patients diagnosed between 2012 and 2019. Multivariable Cox models adjusting for baseline characteristics and receipt of targeted and immunotherapy were utilised to explore the relationship between these variables and changes in the hazard of death by calendar year in each cohort. Results: We identified cohorts of 30,076 (54.7% Males) non-biomarker positive and 652 (45.4% males) ALK+ mNSCLC cancer patients in the database eligible for the analysis. Survival in both cohorts improved over time. After adjustment for differences in baseline characteristics the hazard of death in non-biomarker positive patients diagnosed in 2015, 2016, 2017, 2018 and 2019 was observed to be 14%, 13%, 16% 19% and 21% lower respectively than that in 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 innovative treatments. Similarly, decreases in the hazard of death were only observed in ALK+ patients diagnosed in 2018 and 2019 relative to 2012 and were no longer observed following adjustment for the use of ALK inhibitors. Conclusions: Our findings expand on the SEER data and provide direct evidence linking improvements in survival of NSCLC patients over the past decade with the introduction of innovative therapies.