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

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.

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.

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.

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.