Prospective validation study of nutritional and immunological predictors in immune checkpoint inhibitor efficacy for non‐small cell lung cancer

Immune checkpoint inhibitors (ICIs) have improved prognosis in non‐small cell lung cancer (NSCLC). This prospective observational study aimed to validate the clinical impact of nutritional and immunological indices, including neutrophil‐to‐lymphocyte ratio (NLR), Glasgow prognostic score (GPS), prognostic nutritional index (PNI), controlling nutritional status (CONUT), and skeletal muscle area (SMA) in NSCLC patients treated with first‐line ICIs. Three hundred and one patients with programmed cell death‐ligand 1 (PD‐L1) expression data were enrolled. SMA was measured using computed tomography images at the L3 level. Cut‐off values were determined by our previous retrospective reports. The primary endpoint was progression‐free survival (PFS). As a translational research, 15 myokines were evaluated from pre‐treatment blood samples. The NLR, GPS, PNI, CONUT, and SMA were all significantly associated with PFS ( p = .0128, p = .0016, p = .0046, p = .0485, and p = .0161, respectively). Multivariate analysis elucidated that age ≥75 years ( p = .0256), male sex ( p = .0227), combined chemotherapy ( p = .0002), PD‐L1 ≥50% ( p = .0017), and SMA ( p = .0354) were significant predictors of objective response. Multivariate analysis of PFS showed that performance status ( p = .0104), PD‐L1 ( p <.0001), GPS ( p = .0042), and SMA ( p = .0367) were independent predictors. FSTL‐1 was significantly lower in non‐responders than in responders ( p = .0212). In conclusion, the nutritional and immunological indices were validated to be significant predictors for the efficacy of ICIs. SMA was a predictor of both objective response and PFS, highlighting FSTL‐1 as a potential biomarker for response to ICIs.