Prognostic Value of Baseline HbA1c in Advanced Non-Small Cell Lung Cancer Patients Treated with PD-1/PD-L1 Inhibitors: A Retrospective Cohort Study

Background Immune checkpoint blockade has become routine for advanced non-small cell lung cancer (NSCLC), but patient benefit is heterogeneous. In everyday practice, it is uncertain whether pretreatment glycemic exposure—reflected by glycosylated hemoglobin (HbA1c)—tracks with response to PD-1/PD-L1–based therapy. We therefore assessed baseline HbA1c in relation to outcomes in advanced NSCLC. Methods We assembled a retrospective cohort of 173 consecutive patients with stage IIIB–IV NSCLC treated with immune checkpoint inhibitors at Lu'an Hospital of Anhui Medical University. Patients were grouped by baseline HbA1c (< 6.5% vs ≥ 6.5%). Progression-free survival (PFS) was the primary outcome; objective response rate (ORR), disease control rate (DCR), and immune-related safety were evaluated as secondary outcomes. Time-to-event outcomes were examined using Kaplan–Meier curves, and associations were quantified in Cox regression models with multivariable adjustment. Results Baseline HbA1c was ≥ 6.5% in 114 patients (65.9%). During a median follow-up of 17.8 months, the high-HbA1c group had shorter PFS than the low-HbA1c group (log-rank P < 0.001) and a substantially lower ORR (9.6% vs 37.3%, P < 0.001). After adjustment for liver metastasis, BMI, ECOG performance status and other covariates, HbA1c ≥ 6.5% remained associated with progression (HR = 1.81; 95% CI, 1.21–2.70; P = 0.004). Higher neutrophil-to-lymphocyte ratio (NLR) was also associated with poorer PFS (HR = 1.31, P = 0.005). Findings were similar in subgroup analyses, including patients without liver metastasis. Immune-related adverse events occurred at comparable frequencies between groups (P = 0.170). Conclusion Elevated baseline HbA1c (≥ 6.5%) identifies advanced NSCLC patients who, on average, experience shorter PFS and lower response rates with PD-1/PD-L1–based therapy. The signal persists after clinical adjustment and accompanies an inflammatory phenotype (higher NLR), supporting HbA1c as a simple pretreatment risk marker.