Comprehensive Statistical Exploration of Prognostic (Bio-)Markers for Responses to Immune Checkpoint Inhibitor in Patients with Non-Small Cell Lung Cancer

SIMPLE SUMMARY: Metastatic non-small cell lung cancer (NSCLC) patients treated with immune checkpoint inhibitors (ICIs) may suffer from heavy side effects, and not all patients benefit from the treatment. Therefore, it is crucial to gain knowledge about possible (bio-)markers for response to ICIs. We used retrospective data acquired from NSCLC patients treated with ICIs in first- or further-line therapy settings, including 16 possible markers. We conducted a comprehensive statistical analysis study to find markers for response to treatment, assessed the robustness of our results, and discussed often encountered statistical pitfalls. Our study yielded hypotheses for various predictive and prognostic (bio-)markers for response to ICIs in NSCLC patients. In particular, we found that high basophil counts may be predictive for treatment response in patients in further-line therapy settings. ABSTRACT: Metastatic non-small cell lung cancer (NSCLC) patients treated with immune checkpoint inhibitors (ICIs) may suffer from heavy side effects and not all patients benefit from the treatment. We conducted a comprehensive statistical analysis to identify promising (bio-)markers for treatment response. We analyzed retrospective data from NSCLC patients treated with ICIs in first- or further-line therapy settings at the University Hospital Zurich. We investigated 16 possible prognostic markers with respect to overall survival, tumor size reduction, and the development of an immune-related adverse event (irAE) and assessed the robustness of our results. For the further-line patient group, the most significant result was that increased basophil counts were associated with increased odds of tumor size reduction within three months and with the development of an irAE. For the first-line patient group, the most significant results were that increased lymphocyte counts, the histology of adenocarcinoma, and the intake of non-steroidal anti-rheumatic drugs (NSAR) were associated with decreased hazards of dying. Our study yielded new hypotheses for predictive (bio-)markers for response to ICIs in NSCLC patients. The possibly beneficial role of high basophil counts is a particularly interesting finding. Our results should be tested on independent data in a prospective fashion.