e20584 Background: Immune checkpoint inhibitor (ICI) monotherapy (mono) or combined with chemotherapy (CT) is standard first-line (1 st -L) therapy for advanced NSCLC. However, choosing optimal strategies in real-world settings remains challenging. Methods: We screened the China National Cancer Center Database (609 hospitals, 29 provinces) for stage IIIC/IV (AJCC 8th) EGFR/ALK wild-type NSCLC patients registered 2019-2024, who received 1 st -L ICI±CT. Clinical characteristics and survival outcomes were analyzed. Results: 1,107 patients were included. PD-L1 Tumor Proportion Score (TPS) was as follows: <1% (24.1%), 1-49% (39.4%), and ≥50% (36.5%). Brain metastases (M) occurred in 231 patients (20.9%), liver M in 111 (10.0%). 1 st -L therapy included ICI-mono (10.6%) and ICI+CT (89.4%). In the ICI+CT cohort, the median overall survival (mOS) was similar between TPS 1-49% and <1% groups (19.65 vs. 18.46 months; hazard ratio HR 0.91, 95% confidence interval CI: 0.73-1.14, P =0.43). However, in TPS ≥50% group, ICI+CT did not improve mOS vs. ICI-mono (26.64 vs. 26.15 months; HR 0.93, 95% CI: 0.60-1.43, P =0.73). OS multivariate analysis (Table 1) showed that in total population and ICI+CT cohort, older age, male and liver metastases were independent adverse prognostic factors, while TPS ≥50% was favorable. In TPS ≥50% group, older age remained adverse and liver M trended toward poor prognosis. Brain M were not adverse prognostic factor in any populations. Conclusions: This real-world study confirms advanced NSCLC patients with PD-L1 TPS <1% had similar OS to TPS 1-49% on 1 st -L ICI+CT. Though TPS ≥50% patients had better OS with ICI+CT, adding CT to ICI did not improve outcomes further. In immunotherapy era, older age and liver M were adverse prognostic factors; brain M were not. Multivariate analysis of OS. Total ICI+CT TPS ≥ 50% N HR (95%CI) P N HR (95%CI) P N HR (95%CI) P Age <65 627 Ref. 574 Ref. 230 Ref. 65-74 382 1.41(1.17，1.70) <0.001 338 1.38(1.14-1.68) 0.0012 142 1.51(1.07-2.14) 0.02 75-84 70 1.43(0.99，2.07) 0.057 57 1.34(0.88-2.03) 0.17 23 2.27(1.24-4.16) 0.0077 ≥85 28 4.03(2.54，6.38) <0.001 21 4.16(2.44-7.09) <0.001 9 5.30(2.37-11.82) <0.001
Gu et al. (Thu,) studied this question.