Real-world study of first-line immunotherapy for EGFR/ALK wild-type advanced NSCLC: Analysis from the China National Cancer Center database.

Abstract

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 Sex Female 230 Ref. 202 Ref. 72 Ref. Male 877 1.48(1.17，1.88) 0.0013 788 1.55(1.21-2.00) <0.001 332 0.84(0.56-1.26) 0.40 Stage IIIC 60 Ref. 53 Ref. 27 Ref. IV 1047 1.45(0.94，2.23) 0.095 937 1.48(0.92-2.37) 0.10 377 1.20(0.58-2.47) 0.62 Liver Yes 111 1.43(1.10，1.86) 0.0071 105 1.44(1.10-1.89) 0.0081 29 1.63(0.98-2.72) 0.059 Brain Yes 231 0.87(0.70，1.09) 0.22 217 0.90(0.72-1.12) 0.34 87 0.97(0.66-1.42) 0.86 Treatment ICI 117 Ref. - - 66 Ref IO+CT 990 1.07(0.79，1.46) 0.66 - - 338 1.09(0.70-1.71) 0.70 TPS <1% 267 Ref. 255 Ref. - - 1-49% 436 0.93(0.75，1.16) 0.52 397 0.97(0.77-1.21) 0.78 - - ≥50% 404 0.65(0.57，0.82) <0.001 338 0.66(0.52-0.84) <0.001 - -