Elucidation of the Application of Blood Test Biomarkers to Predict Immune-Related Adverse Events in Atezolizumab-Treated NSCLC Patients Using Machine Learning Methods.

Background

Development of severe immune-related adverse events (irAEs) is a major predicament to stop treatment with immune checkpoint inhibitors, even though tumor progression is suppressed. However, no effective early phase biomarker has been established to predict irAE until now.

Method

This study retrospectively used the data of four international, multi-center clinical trials to investigate the application of blood test biomarkers to predict irAEs in atezolizumab-treated advanced non-small cell lung cancer (NSCLC) patients. Seven machine learning methods were exploited to dissect the importance score of 21 blood test biomarkers after 1,000 simulations by the training cohort consisting of 80%, 70%, and 60% of the combined cohort with 1,320 eligible patients.

Results

XGBoost and LASSO exhibited the best performance in this study with relatively higher consistency between the training and test cohorts. The best area under the curve (AUC) was obtained by a 10-biomarker panel using the XGBoost method for the 8:2 training:test cohort ratio (training cohort AUC = 0.692, test cohort AUC = 0.681). This panel could be further narrowed down to a three-biomarker panel consisting of C-reactive protein (CRP), platelet-to-lymphocyte ratio (PLR), and thyroid-stimulating hormone (TSH) with a small median AUC difference using the XGBoost method [for the 8:2 training:test cohort ratio, training cohort AUC difference = -0.035 (p < 0.0001), and test cohort AUC difference = 0.001 (p=0.965)].

Conclusion

Blood test biomarkers currently do not have sufficient predictive power to predict irAE development in atezolizumab-treated advanced NSCLC patients. Nevertheless, biomarkers related to adaptive immunity and liver or thyroid dysfunction warrant further investigation.

Informations de copyright

Copyright © 2022 Zhou, Wong, Wang, Tan, Chen, Jin, He, Shen, Wang, Frey, Fietkau, Hecht, Ma and Gaipl.

Déclaration de conflit d'intérêts

AHW is a founder and shareholder of AW Medical Company Limited. MH reports collaborations with Merck Serono (advisory role, speakers’ bureau, honoraria, travel expenses, and research funding), MSD (advisory role, speakers’ bureau, honoraria, travel expenses, and research funding), AstraZeneca (research funding), Novartis (research funding), BMS (advisory role, honoraria, and speakers’ bureau), and Teva (travel expenses). UG and RF received support for presentation activities for Dr Sennewald Medizintechnik GmbH, have received support for investigator initiated clinical studies (IITs) from MSD and AstraZeneca, and contributed at Advisory Boards Meetings of AstraZeneca and Bristol-Myers Squibb. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.