Predictive and prognostic significance of PIOS (Patras Immunotherapy Score) model in patients with advanced NSCLC treated with nivolumab or pembrolizumab: Results from a validation cohort.

Abstract

e21164 Background: The treatment of advanced non-small cell lung cancer (aNSCLC) has tremendously changed during the last few years, especially, since immune checkpoint inhibitors (ICIs) were incorporated in the daily clinical practice. However, clinical useful biomarkers remain an unmet need. Recently, our group established and proposed a new score, Patras Immunotherapy Score (PIOS), which was found to have predictive and prognostic value in a discovery group with aNSCLC patients treated with nivolumab or pembrolizumab. The objective of the current study was to validate our initial observation and confirm the clinical significance of PIOS formula in an external and multicentric cohort of aNSCLC patients. Methods: PIOS is a baseline formula derived by combining the following non-interventional clinical parameters, Performance Status (PS), Body Mass Index (BMI), age and Line Of Treatment (LOT) and it is calculated as PIOS = (PS×BMI)/(LOT×AGE). In the current multicenter study, 626 aNSCLC patients, treated with nivolumab or pembrolizumab monotherapy, were retrospectively selected, blindly to the clinical outcome, and enrolled. The primary endpoints of this study were to investigate the predictive and prognostic value of PIOS in terms of progression free survival (PFS), overall survival (OS) and best overall response. Results: Firstly, PIOS was associated with best overall response. Following a two-tier model, patients who had progressed (PD) had lower scores than those with stable disease (SD), partial response (PR) or complete response (CR) (p < 0.001). This association remained significant using a four-tier model (PD, SD, PR and CR) for evaluation of best overall response (p < 0.001). In addition, predictive significance of PIOS score also persisted using a binary logistic regression analysis, adjusted for disease stage and PD-L1 status (p = 0.002, OR 0.578, 95% CI 0.408-0.821). Furthermore, patients with higher PIOS score had longer PFS compared to patients with lower PIOS score (ΗΡ 0.621, 95% CI 0.470-0.821, p = 0.001), while multivariate analysis for PFS, adjusted for clinical stage and PD-L1, confirmed the predictive value of PIOS score (HR 0.651, 95% CI 0.492-0.863, p = 0.003). Moreover, PIOS score was also associated with prognosis (p < 0.001). The median OS for the favorable group was 778 days compared to 341 days for the unfavorable group with low PIOS score (HR = 0.608, 95% CI 0.482-0.766, p < 0.001) at univariate analysis. This association remained statistically significant (HR 0.620, 95% CI 0.492-0.783, p < 0.001) after adjusting for PD-L1 expression. Conclusions: These data provide further validation for PIOS as predictive and prognostic biomarker in aNSCLC patients treated with nivolumab or pembrolizumab monotherapy.