Prognostic biomarkers in lung cancer patients treated with immunotherapy

Abstract

Background: Immunotherapy modified advanced lung cancer treatment. Unfortunately, not all patients respond to it and little is known about predictive markers of response. Recently, a lung immune prognostic index (LIPI) was developed to predict outcomes. Neutrophil-lymphocyte ratio (NLR) has also been shown as possible marker of response to immune checkpoint inhibitors. The aim of this study is to evaluate the prognostic value of both LIPI and NLR in patients with advanced lung cancer treated with anti-PD1 drugs, pembrolizumab and nivolumab. Methods: Data from patients diagnosed with lung cancer (stage III-IV) treated with pembrolizumab and nivolumab, from a Portuguese tertiary cancer centre were reviewed retrospectively (July'15 to July'19). LIPI and NLR were calculated before the beginning of immune checkpoints inhibitors. NLR was calculated as the ratio between neutrophils and lymphocytes. NLR was categorized into low (≤ median NLR in our cohort) and high NLR (>median). LIPI score results from NLR and LDH level and has 3 different risk categories: low, intermediate and high. Univariate analysis and multivariable analysis (Cox model adjusted for age, EGFR status, PD-L1 expression and previous treatment) were done to evaluate the association between LIPI and NLR with time to progression (TTP) and overall survival (OS). Results: In our cohort, 120 patients were treated, according to PD-L1 expression, with pembrolizumab (83) and nivolumab (37). Median follow-up in living patients was 13 months, having occurred 60 deaths and 54 disease progression. In both univariate (p = 0.019) and multivariable (p = 0.001) analysis, LIPI score was an independent prognostic factor for OS but not for TTP. HR for intermediate vs low LIPI score was 3.1 (95%CI 1.1-8.8) and HR for high vs low LIPI score was 7.5 (95% CI = 2.5-22.8). Similarly, in univariate (p = 0.007) and multivariable (p = 0.006) analysis, NLR was an independent prognostic factor for OS but not for TTP. HR for high NLR was 2.9 (95% CI = 1.3-6.4). Conclusion: In our cohort of patients, both LIPI score and NLR are prognostic factors for overall survival in advanced lung cancer patients treated with pembrolizumab and nivolumab. Prospective studies are needed to validate the value of these biomarkers in immunotherapy. Legal entity responsible for the study: The authors. Funding: Has not received any funding. Disclosure: All authors have declared no conflicts of interest.