Abstract / Summary
Background/Objectives: Immune checkpoint inhibitors have become a standard treatment option for advanced/metastatic non-small cell lung cancer (NSCLC); however, considerable heterogeneity exists among patients regarding treatment response and survival. This study aimed to determine whether the pretreatment modified Glasgow Prognostic Score (mGPS), a marker of systemic inflammation and nutritional status, is prognostically associated with progression-free survival (PFS) and overall survival (OS) in patients with advanced/metastatic NSCLC treated with nivolumab at a single tertiary oncology center. Methods: This retrospective, single-center cohort study included 130 adult patients with histologically confirmed advanced/metastatic NSCLC who received nivolumab at the Department of Medical Oncology, Çukurova University Faculty of Medicine. The pretreatment mGPS (0, 1, or 2), derived from baseline serum C-reactive protein (CRP) and albumin levels, was analyzed in relation to PFS and OS using the Kaplan–Meier method, log-rank test, and Cox proportional hazards regression. The prognostic value of mGPS was tested in multivariable Cox models adjusted for age, sex, Eastern Cooperative Oncology Group (ECOG) performance status, histology, brain metastasis, liver metastasis, and neutrophil-to-lymphocyte ratio (NLR); the proportional hazards assumption was formally tested, and the incremental discriminative contribution of mGPS was assessed using bootstrap resampling. Results: Among 130 patients, 83.8% received nivolumab as second-line therapy. Pretreatment mGPS was 0, 1, and 2 in 40 (30.8%), 55 (42.3%), and 35 (26.9%) patients, respectively. Median OS was not reached, 9.7 months, and 3.0 months across mGPS 0, 1, and 2, respectively; corresponding median PFS values were 10.2, 4.8, and 3.0 months (log-rank p < 0.001 for both endpoints). After adjustment for age, sex, ECOG performance status, histology, brain metastasis, liver metastasis, and NLR, each one-point increase in mGPS remained associated with worse OS (adjusted HR 2.38; 95% CI 1.64–3.46; p < 0.001) and PFS (adjusted HR 1.81; 95% CI 1.32–2.48; p < 0.001), independent of the covariates included in the model. The proportional hazards assumption held for mGPS in both models. Addition of mGPS to the clinical-variables-only model was associated with higher model discrimination (Harrell’s C-index: 0.676 to 0.737 for OS and 0.620 to 0.666 for PFS), a difference confirmed as statistically significant by bootstrap resampling (2000 iterations; 95% CI for the difference excluding zero, p < 0.001 for both endpoints). Conclusions: Pretreatment mGPS is a simple, readily available marker that shows a robust prognostic—rather than treatment-predictive—association with both OS and PFS in patients with advanced/metastatic NSCLC treated predominantly as second-line nivolumab monotherapy. Its addition to established clinical variables was associated with a statistically significant, though modest, improvement in prognostic discrimination. These findings require prospective, multicenter validation, including in first-line immunotherapy settings, before mGPS can be recommended for routine clinical risk stratification.