Abstract 5946: Five-year real-world survival outcomes of patients with advanced non-small cell lung cancer receiving first-line immunotherapy-based regimens

Abstract Background: Five-year real-world outcomes of first-line (1L) immunotherapy (IO)-based regimens for advanced non-small cell lung cancer (aNSCLC) were assessed to describe how real-world outcomes correspond to those in clinical trials. Methods: Adult patients (pts) with aNSCLC from Flatiron Health database receiving 1L IO monotherapy or single-agent IO + chemotherapy from Jan 1, 2016 to Jun 30, 2024 were identified. Pts were excluded if they had EGFR/ALK mutations or unknown histology type. Overall survival (OS) and real-world progression-free survival (rwPFS) of each 1L treatment were described using Kaplan-Meier analyses. Results: A total of 17, 070 pts with aNSCLC were included (6, 039 pts receiving IO monotherapy; 11, 031 pts receiving IO + chemotherapy). Among pts receiving IO monotherapy, the 1-, 2-, 3-, 4-, and 5-year OS rates were 52.7%, 36.4%, 27.3%, 21.6%, and 17.5% and the rwPFS rates were 29.5%, 18.0%, 13.2%, 10.0%, and 7.8% respectively. Among pts receiving IO + chemotherapy, the 1-, 2-, 3-, 4-, and 5-year OS rates were 51.0%, 32.9%, 24.0%, 19.4%, and 15.8% and the rwPFS rates were 27.6%, 15.6%, 10.6%, 8.3%, and 6.9%, respectively. Table 1 Table 1: 5-year OS and rwPFS rates 1L IO monotherapy 1L IO+chemotherapy PD-L1<1%N=426 PD-L1 1-49%N=1, 040 PD-L1≥50%N=3, 861 PD-L1<1%N=3, 399 PD-L1 1-49%N=3, 265 PD-L1≥50%N=1, 939 OS (5-year rate, %) 14.2 11.2 20.0 11.2 15.0 25.2 OS by histology type (5-year rate, %) Squamous 12.4 6.2 10.7 11.0 10.9 19.4 Non-squamous 15.0 14.3 23.1 11.3 16.1 26.2 OS by ECOG performance status (5-year rate, %) 0-1 15.1 15.4 23.5 13.1 16.9 27.0 ≥2 7.5 NA 11.1 3.6 8.8 13.9 rwPFS (5-year rate, %) 6.3 5.0 9.0 3.7 5.3 14.1 rwPFS by histology type (5-year rate, %) Squamous 7.6 2.9 5.1 4.2 6.0 10.6 Non-squamous 5.3 6.3 10.2 3.6 5.1 14.7 rwPFS by ECOG performance status (5-year rate, %) 0-1 7.0 7.0 10.6 4.8 5.6 15.3 ≥2 NA NA 5.0 1.1 3.3 7.7 presents the 5-year OS and rwPFS rates stratified by histology type, tumor programmed death ligand 1 (PD-L1) expression level, and Eastern Cooperative Oncology Group (ECOG) performance status. Pts with lower PD-L1 expression level (<1%), worse ECOG performance status (≥2), and squamous cell carcinoma had worse survival outcomes, regardless of the type of 1L treatment. Conclusions: Five-year real-world survival rates for pts with aNSCLC treated with 1L IO-based regimens were lower than those observed in pivotal trials, indicating an unmet need for the management of newly-diagnosed aNSCLC. New strategies are needed to treat aNSCLC. This gap is especially pronounced in pts with squamous histology or PD-L1 <1% emphasizing the need for new treatment strategies for these high-risk groups. Citation Format: David Waterhouse, Amanda Shawky, Aanal Desai, Keith A. Betts, Manasvi Sundar, Reginald Villacorta, David Stenehjem. Five-year real-world survival outcomes of patients with advanced non-small cell lung cancer receiving first-line immunotherapy-based regimens [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 5946.