Predicting Survival of NSCLC Patients Treated with Immune Checkpoint Inhibitors: Impact and Timing of Immune-related Adverse Events and Prior Tyrosine Kinase Inhibitor Therapy

Authors

Michael R. Sayer, Chapman UniversityFollow
Isa Mambetsariev, City of Hope National Medical Center
Kun-Han Lu, City of Hope National Medical Center
Chi Wah Wong, City of Hope National Medical Center
Ashley Duche, Chapman UniversityFollow
Richard Beuttler, Chapman UniversityFollow
Jeremy Fricke, City of Hope National Medical Center
Rebecca Pharaon, City of Hope National Medical CenterFollow
Leonidas Arvanitis, City of Hope National Medical CenterFollow
Zahra Eftekhari, City of Hope National Medical Center
Arya Amini, City of Hope National Medical Center
Marianna Koczywas, City of Hope National Medical Center
Erminia Massarelli, City of Hope National Medical Center
Moom Rahman Roosan, Chapman UniversityFollow
Ravi Salgia, City of Hope National Medical Center

Document Type

Article

Publication Date

2-13-2023

Abstract

Introduction: Immune checkpoint inhibitors (ICIs) produce a broad spectrum of immune-related adverse events (irAEs) affecting various organ systems. While ICIs are established as a therapeutic option in non-small cell lung cancer (NSCLC) treatment, most patients receiving ICI relapse. Additionally, the role of ICIs on survival in patients receiving prior targeted tyrosine kinase inhibitor (TKI) therapy has not been well-defined.

Objective: To investigate the impact of irAEs, the relative time of occurrence, and prior TKI therapy to predict clinical outcomes in NSCLC patients treated with ICIs.

Methods: A single center retrospective cohort study identified 354 adult patients with NSCLC receiving ICI therapy between 2014 and 2018. Survival analysis utilized overall survival (OS) and real-world progression free survival (rwPFS) outcomes. Model performance matrices for predicting 1-year OS and 6-month rwPFS using linear regression baseline, optimal, and machine learning modeling approaches.

Results: Patients experiencing an irAE were found to have a significantly longer OS and rwPFS compared to patients who did not (median OS 25.1 vs. 11.1 months; hazard ratio [HR] 0.51, confidence interval [CI] 0.39- 0.68, P-value <0.001, median rwPFS 5.7 months vs. 2.3; HR 0.52, CI 0.41- 0.66, P-value <0.001, respectively). Patients who received TKI therapy before initiation of ICI experienced significantly shorter OS than patients without prior TKI therapy (median OS 7.6 months vs. 18.5 months; P-value < 0.01). After adjusting for other variables, irAEs and prior TKI therapy significantly impacted OS and rwPFS. Lastly, the performances of models implementing logistic regression and machine learning approaches were comparable in predicting 1-year OS and 6-month rwPFS.

Conclusion: The occurrence of irAEs, the timing of the events, and prior TKI therapy were significant predictors of survival in NSCLC patients on ICI therapy. Therefore, our study supports future prospective studies to investigate the impact of irAEs, and sequence of therapy on the survival of NSCLC patients taking ICIs.

Comments

This article was originally published in Frontiers in Oncology, volume 13, in 2023. https://doi.org/10.3389/fonc.2023.1064169

Recommended Citation

Sayer MR, Mambetsariev I, Lu K-H, Wong CW, Duche A, Beuttler R, Fricke J, Pharoan R, Arvanitis L, Eftekhari Z, Amini A, Koczywas M, Massarelli E, Roosan MR and Salgia R (2023) Predicting survival of NSCLC patients treated with immune checkpoint inhibitors: Impact and timing of immune-related adverse events and prior tyrosine kinase inhibitor therapy. Front. Oncol. 13:1064169. https://doi.org/10.3389/fonc.2023.1064169

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The authors

Creative Commons License

This work is licensed under a Creative Commons Attribution 4.0 License.