Background In advanced non-small cell lung cancer, the efficacy of PD-1/PD-L1 (programmed cell death protein 1/programmed death-ligand 1) inhibitors varies considerably, and early prognostic predictors remain unclear.

Objective To evaluate the prognostic significance of early changes in the neutrophil-to-lymphocyte ratio (ΔNLR), prognostic nutritional index (PNI), and their combination as the inflammation-nutrition score (INS) in advanced non-small cell lung cancer (NSCLC) patients receiving PD-1 inhibitor therapy.

Methods A retrospective analysis was conducted on patients with advanced NSCLC who received anti-PD-L1 monoclonal antibody monotherapy or combination therapy at Shandong Second Medical University Affiliated Hospital from January 2020 to December 2024. Peripheral blood indexes were measured before treatment and after completing two treatment cycles. ΔNLR and PNI were calculated and used to group the patients: ΔNLR ≥ 20% as the elevated group, < 20% as the stable group; PNI ≥ 45 as the well-nourished group, < 45 as the malnourished group; INS was defined as a combined indicator: ΔNLR ≥20% scored 1 point, PNI < 45 scored 1 point. Patients were stratified into high-risk (2 points), intermediate-risk (1 point), and low-risk (0 points) groups. Kaplan-Meier method was used to compare progression-free survival (PFS) and overall survival (OS) among the groups, and Cox regression was applied to identify independent prognostic factors. A prognostic prediction model was then constructed, and the prediction performance was evaluated using receiver operating characteristic (ROC) curve analysis.

Results A total of 163 patients with NSCLC were included in this study, comprising 100 males (61.35%) and 63 females (38.65%). The median age was 61 (range: 54-68) years. Median OS was 16.4 (IQR: 11.8-22.0) months, and median PFS was 7.8 (IQR: 5.0-14.0) months.Compared with the stable group, the elevated NLR group had significantly shorter median PFS (6.5 IQR: 4.1-11.5 months vs 8.6 IQR: 6.2-15.9 months, P=0.041). The group with PNI < 45 had shorter PFS than the PNI ≥45 group (6.9 IQR: 4.3-12.9 months vs 8.9 IQR: 6.2-17.5 months, P=0.048). Similarly, the INS high‑risk group showed reduced PFS compared with the intermediate and low‑risk group (6.0 IQR: 4.2-9.2 months vs 8.4 IQR: 6.1-13.7 months, P=0.047). Multivariate Cox regression analysis revealed that ΔNLR ≥ 20%, PNI < 45, and INS high‑risk status were associated with shorter PFS, whereas PD‑L1 expression ≥50% was associated with relatively better PFS (P < 0.05). ROC curve analysis showed that models based on ΔNLR+PNI+PD‑L1 and INS+PD‑L1 both exhibited good predictive performance for PFS in patients with advanced NSCLC, with areas under the curve (AUC, 95% CI) of 0.852 (0.753-0.937) and 0.843 (0.698-0.978), respectively.

Conclusion Early‑treatment increases in ΔNLR and decreases in PNI are significantly associated with poorer prognosis in NSCLC patients receiving PD‑L1 inhibitor therapy. INS may serve as a composite indicator reflecting inflammatory and nutritional status, providing reference for evaluating immunotherapy efficacy and prognosis.