Neutrophil-to-lymphocyte ratio-based prognostic score can predict outcomes in patients with advanced non-small cell lung cancer treated with immunotherapy plus chemotherapy

Abstract

Backgroud: Immune checkpoint inhibitor (ICI) plus chemotherapy has become the standard of care for advanced non-small cell lung cancer (NSCLC). Nonetheless, reliable efficacy biomarkers of ICI plus chemotherapy are lacking. In this research, we sought to explore efficacy biomarkers and construct robust prognostic models in NSCLC patients treated with ICI plus chemotherapy.

Methods: We retrospectively analyzed 171 patients with advanced NSCLC treated with ICI plus chemotherapy. Clinical characteristics and peripheral blood inflammatory indexes were collected and prognostic models were constructed to explore efficacy and prognosis biomarkers of ICI plus chemotherapy.

Results: In the cohort that received first-line ICI plus chemotherapy, pre-treatment neutrophil-to-lymphocyte ratio (NLR) > 3.3 and fibrinogen (FIB) > 3.196 were associated with worse efficacy and were independent risk factors of progression-free survival (PFS). Compared to programmed cell death ligand 1 (PD-L1), the derived NLR-FIB (NF) score had significantly improved accuracy in predicting efficacy and prognosis. In advanced NSCLC patients with targetable oncogenic driver alterations receiving second- or post-line ICI plus chemotherapy, pre-treatment NLR > 3.53 was associated with worse efficacy and was an independent risk factor of PFS and OS; Tyrosine kinase inhibitor (TKI)-PFS > 12 months were independent risk factors of overall survival (OS). Secondary epidermal growth factor receptor (EGFR)-T790M mutation, platelet-to-lymphocyte ratio (PLR) > 196.81 and albumin (ALB) < 40.25 were associated with worse PFS. Based on NLR and TKI-PFS, an NLR-TKI-PFS (NTP) score was constructed with three OS risk prognosis categories: favorable, intermediate, and poor (corresponding to a median OS of 21, 12, and 5.3 months).

Conclusions: The noninvasive NF score, combining NLR > 3.3 and FIB > 3.196, was superior to PD-L1 estimated from tumor tissue in predicting the efficacy and prognosis of first-line ICI plus chemotherapy in advanced NSCLC patients. The noninvasive NTP score, combining NLR > 3.53 and TKI-PFS > 12 months, is a valuable tool for predicting OS and PFS in advanced NSCLC patients with targetable oncogenic driver alterations receiving second- or post-line ICI combination therapy.

Keywords: Efficacy prediction; Immunochemotherapy; Neutrophil lymphocyte ratio; Non-small cell lung cancer; Prognostic biomarker.

Fig. 1

Treatment response of first-line ICI plus chemotherapy according to (A) Histology; (B) NLR level; (C) FIB level; (D) NF score. (E) ROC curves of the NLR, FIB, PD-L1, NF score and NFP score to predict DCR

Fig. 2

Kaplan–Meier curves for progression-free survival (PFS) of first-line ICI plus chemotherapy according to (A) Clinical stage; (B) NLR level; (C) FIB level; (D) HGB level; (E) CRP level; (F) LDH level; (G) D-Dimer level; (H) CD4/CD8 + T lymphocyte ratio; (I) NF score. (J) ROC curves of the NLR, FIB, PD-L1, NF score and NFP score to predict PFS

Fig. 3

Dynamic changes in NLR level (A) and FIB level (B) before (pre) and after (post) first-line ICI plus chemotherapy for patients with paired blood samples

Fig. 4

Kaplan–Meier curves for Overall survival (OS) of second- or post-line ICI combination therapy according to (A) TKI-PFS; (B) NLR level. Kaplan–Meier curves for PFS according to (C) Secondary T790M mutation; (D) NLR level; (E) PLR level; (F) ALB level. (G) Kaplan–Meier curves for OS according to NTP score. (H) Kaplan–Meier curves for PFS according to NTP score. (I) ROC curves of the NLR, TKI-PFS and NTP score to predict OS

Fig. 5

Dynamic changes in NLR level before (pre) and after (post) second- or post-line ICI combination therapy for patients with paired blood samples