Background: Clinical outcomes in patients with mNSCLC have improved post-approval of immunotherapy (IO). However, limited real-world data exists describing the evolution of treatment patterns and impact on outcomes in later lines of therapy (LOT). Here we describe the treatment landscape and outcomes of patients with mNSCLC without driver mutations within community oncology settings. Methods: This retrospective observational study included adult patients with mNSCLC who initiated first LOT (LOT1) for mNSCLC in the US Oncology Network from 1/1/2015 to 12/31/2020 (followed through 3/31/2022), using structured electronic health records. Patients who initiated LOT1 with a targeted therapy or EGFR/ALK/ROS1 inhibitor during any LOT were excluded. Second, third, and fourth LOT (LOT2, LOT3, LOT4) were assigned using start and stop dates. Treatment patterns up to LOT4 were summarized descriptively by period of treatment initiation (early-IO period: 2015–2017; post-IO period: 2018–2020). Overall survival (OS) and time to next treatment (TTNT) were assessed by LOT using Kaplan-Meier analysis. Results: Overall, 11,035 patients met study criteria, of which 3,835 (35%) patients initiated LOT2, 1,264 (11%) patients initiated LOT3, and 393 (4%) patients initiated LOT4 between 2015 and 2020, respectively. From 2015–2017 to 2018–2020, pembrolizumab plus platinum chemotherapy with pemetrexed or paclitaxel as LOT1 increased from 3% (n = 176) to 42% (n = 2,448), and pembrolizumab monotherapy increased from 9% (n = 465) to 26% (n = 1,518). In patients who initiated LOT2, IO followed by docetaxel ± ramucirumab increased from 1% (n = 15) to 15% (n = 295), whereas this sequence from LOT2 to LOT3 was used in 23% (n = 111) from 2015–2017 and 20% (n = 159) from 2018–2020. Median (95% CI) OS was 13.3 (12.6, 14.0) months vs. 14.7 (13.8, 15.3) months from initiation of LOT1 in 2015–2017 vs. 2018–2020, respectively (P = 0.187). Clinical outcomes by LOT and period of treatment initiation are presented as median (95% CI) in the table below. Conclusions: Understanding evolving treatment patterns in the community oncology setting is important for uncovering opportunities for mNSCLC treatment optimization. This descriptive study reveals the increasing use of mono- and combination IO followed by docetaxel ± ramucirumab in the community setting. Additionally, longer OS was noted in the post-IO period, suggesting possible extended benefits from earlier LOT.