Pretherapeutic prognostic factors for survival under chemoimmunotherapy/immunotherapy of advanced NSCLC patients

BACKGROUND: Checkpoint inhibitor therapy with PD-1/PD-L1-antibodies has significant benefits in non-small-cell lung cancer treatment even in advanced stage IVA/B. While PD-L1 expression in tumor is a weak but relevant predictor of treatment response, impact and interaction of potential prognostic factors like ECOG status, LDH-levels, CRP-levels, and genetic mutations remain so far undefined. This study aims to identify pretherapeutic factors that could help estimate outcome of NSCLC patients undergoing chemoimmunotherapy or mono-immunotherapy. PATIENTS AND METHODS: In our Comprehensive Cancer Centre we retrospectively analyzed two selective patient groups undergoing treatment with mono- or chemoimmunotherapy. 'Super responders' with long-term survival longer than 24 months were contrasted against primary progressors with progression-free survival of less than 10 months. Factors were analyzed with univariate and multivariate statistical methods. RESULTS: In 120 patients fulfilling the inclusion criteria we found signals for five factors with impact on overall survival in univariate analyses: ECOG-status, PD-L1 TPS, serum LDH, serum CRP and KEAP-1 mutation. Multivariate analyses confirmed independent impact. As a confirmatory analysis the impact of these factors on progression-free survival was investigated. Comparable impact was supported by univariate and multivariate analysis. CONCLUSION: A detailed prognostic factor analysis for overall survival and progression-free survival in selected groups of advanced non-small-cell lung cancer patients under chemo- or mono-immunotherapy identified five independent parameters: initial ECOG of zero, non-elevated LDH, non-elevated CRP, pretreatment PD-L1 positivity and absence of KEAP1-mutation. Our findings are especially helpful of estimating early treatment failure with aggressive lung cancer progression. This important investigation will be prospectively confirmed in a larger, more unselected population at our Cancer Centre.