Prognostic significance of neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) in non-small cell lung cancer (NSCLC) treated with immune checkpoint inhibitors

Background: Immunotherapy with programmed death receptor-1 (PD-1) antibodies has changed the paradigm of advanced NSCLC treatment. These checkpoint inhibitors showed better outcomes compared with standard treatment but reliable predictive markers are still lacking. High pre-treatment NLR and PLR have been associated with poor prognosis in several tumor types and recent studies suggest a potential role also in NSCLC. We thus conducted this study to evaluate the prognostic significance of NLR and PLR in our patients. Methods: All patients with locally advanced and metastatic NSCLC treated with nivolumab and pembrolizumab from February 2016 to October 2018 were enrolled. NLR and PLR were determined by the division of neutrophils and platelets by lymphocytes in peripheral blood. Kaplan Meier method and Cox proportional hazardous analysis were conducted to assess the impact of NLR, PLR and other clinical factors on overall survival (OS) and progression free survival (PFS). Results: Thirty-two patients were treated, 20 with nivolumab and 12 with pembrolizumab. Median age was 61 (40-82); 63% were male; 91% had an ECOG PS ≤ 2; 37% received ≥ 2 prior systemic therapies and 78% had stage IV disease. Increased NLR or PLR values above mean were independent predictive factors for decreased PFS (11 vs. 6 months, HR 3.33 95%CI 0.97 - 11.3, p = 0.056 and 12 vs. 6 months, HR 3.9 95%CI 1.19 - 12.8, p = 0.025, respectively). NLR and PLR values higher than percentil 25 were predictive factors, when used in combination, for decreased OS (21 vs. 11 months, HR 12.363 95% CI 1.303 - 117.291, p = 0.028 and 13 vs. 11 months, HR 3.9 95%CI 1.19 - 12.8, p = 0.025, respectively). Other clinical factors (i.e. histology, tobacco use, age, gender, ECOG PS, metastatic sites) did not present any implication for OS and PFS, as determined by multivariate analyses. Conclusions: Elevated pre-treatment NLR and PLR are associated with shorter OS and PFS in our cohort independently of other prognostic factors. Our results reinforce the potencial role of these markers as a predictive factor of poor prognosis for NSCLC patients. Prospective studies are warranted to validate these findings. Legal entity responsible for the study: Susana Rocha Amaral. Funding: Has not received any funding. Disclosure: All authors have declared no conflicts of interest.