Background: Previous studies demonstrated that pts > 80 years (80+), or compromised PS (ECOG PS > 2, PS 2+) are frequently not treated for advanced NSCLC, despite studies demonstrating survival benefit with active therapy. We hypothesized that new therapies (e.g., immunotherapy) have changed practice in these populations. Here, we present new subgroup analysis in pts 80+ or PS2+. Methods: We conducted a retrospective, observational cohort study using the nationwide Flatiron Health electronic health record (EHR)-derived de-identified database to describe 1L treatment patterns from 2011 to 2020 in pts with advanced NSCLC. Pts 80+ could only be included from 2015 as the database suppressed birth years prior to 1935 due to privacy protection. Pts were excluded if there was a > 90-day post-diagnosis gap in EHR data. Treatment groups included PD-1/PD-L1 inhibitor single agent, chemoimmunotherapy, platinum-based doublet +/- VEGF inhibitors (VEGFi), single agent chemotherapy and tyrosine kinase inhibitors (TKIs). Descriptive statistics were used to analyze treatment patterns by year, and the relationship between 1L treatments and variables of interest were tested using Cochran-Armitage trend tests. Results: Of 58,145 pts with advanced NSCLC in the database, 6,528 were 80+ (2015+) and 8,611 had PS2+ at diagnosis (2011+). While the proportion of pts who did not receive any documented treatment has decreased for those 80+ (p < 0.0001), the proportion remains the same in pts with PS2+ (p = 0.78; Table). There was rapid uptake of PD-1/PD-L1 inhibitors as well as chemoimmunotherapy upon FDA approvals in 2016 and 2018, respectively. This correlated with a rapid decrease in platinum-doublet chemotherapy +/- VEGFi and single agent chemotherapy use. Single agent immunotherapy was favored in pts 80+ (Table). TKIs accounted for 9-11% of treatment employed in pts 80+ and 6-8% in pts with PS2+, without notable change across the study period. Conclusions: Real world data from 2011 to 2020 demonstrates rapid incorporation of immunotherapy into 1L treatment for NSCLC pts who are 80+ or PS2+. A substantial proportion of pts in these subgroups (32.8% and 35.1%, respectively) still do not receive treatment.