Prognostic significance of the neutrophil-to-lymphocyte ratio and platelet-to-lymphocyte ratio for advanced non-small cell lung cancer patients with high PD-L1 tumor expression receiving pembrolizumab

BACKGROUND: We investigated the association of peripheral blood inflammatory markers with overall survival (OS) in pembrolizumab treated advanced non-small cell lung cancer (aNSCLC) patients with programmed death ligand 1 (PD-L1) expression ≥50%. Clinical risk factors for development of immune-related adverse events (irAE) were also explored. METHODS: aNSCLC patients with high PD-L1 expression receiving pembrolizumab monotherapy outside of clinical trials were identified retrospectively. All patients were treated at one of six British Columbia Cancer clinics between August 2017 and June 2019. Patients were dichotomized using baseline neutrophil-to-lymphocyte ratio (NLR, </≥6.4) and platelet-to-lymphocyte ratio (PLR, </≥441.8). Factors associated with OS were assessed with Cox proportional hazard models. Logistic regression models were utilized in landmark analysis of risk factors for irAE. RESULTS: Among 220 patients, median age was 70.0 years, 55.0% were female, 40.5% had baseline Eastern Cooperative Oncology Group performance status (ECOG PS) 2/3, and 95.5% received frontline pembrolizumab. Median OS for the cohort was 11.8 months (95% CI: 8.7–15.4). On multivariable analysis, baseline NLR ≥6.4 [hazard ratio (HR): 2.31, 95% confidence interval (CI): 1.46–3.64, P<0.001], baseline PLR ≥441.8 (HR: 2.03, 95% CI 1.22–3.37, P=0.006), and pre-treatment ECOG PS 2/3 (HR: 2.19, 95% CI: 1.48–3.26, P<0.001) were associated with worse OS. The incidence of any grade irAE and irAE grade ≥3 were 40.5% and 12.3%, respectively. ECOG PS 2/3 (vs. 0/1) patients were at 3.76-fold higher risk of developing an irAE by the 8-month landmark (P=0.002). CONCLUSIONS: High NLR and PLR were associated with shorter OS in a cohort of patients receiving largely frontline pembrolizumab for aNSCLC in routine practice. ECOG PS 2/3 was associated with higher risk of developing an irAE. Given that NLR and PLR values are easily obtainable, prospective studies are warranted to confirm their prognostic significance in this patient population and explore a predictive utility.