Chest
Original Research: Lung CancerIncidence of Pneumonitis With Use of Programmed Death 1 and Programmed Death-Ligand 1 Inhibitors in Non-Small Cell Lung Cancer: A Systematic Review and Meta-Analysis of Trials
Section snippets
Methods
We followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement to report this systematic review and meta-analysis.7
Eligible Studies
Our search retrieved 3,504 publications. After excluding duplicates and screening titles of the studies, 108 articles were selected on the basis of relevance to the study topic. After abstract and full article review, 19 distinct trials were included. All studies were published in the last 5 years. We found 12 trials with PD-1 inhibitors (nivolumab: n = 9, pembrolizumab: n = 3) and 7 trials with PD-L1 inhibitors (atezolizumab: n = 5, durvalumab: n = 1, avelumab: n = 1). The reasons for
Discussion
In the present meta-analysis of all published clinical trials of PD-1 and PD-L1 inhibitor therapy for patients with NSCLC, the overall incidence of all grade pneumonitis in PD-1 inhibitor group was 3.6% and in the PD-L1 inhibitor group was 1.3%, a difference that was significant. Grade ≥ 3 pneumonitis incidence was significantly higher for PD-1 inhibitors as well.
Use of PD-1 and PD-L1 inhibitors in the frontline setting was associated with significantly higher incidence of all grade pneumonitis
Conclusions
This analysis suggests that PD-1 inhibitors are associated with a significantly higher incidence of pneumonitis than PD-L1 inhibitors. This finding may impact clinical selection of these agents given their overlapping indications in NSCLC. Further understanding of the role of PD-1 and its ligands in generating pneumonitis can yield important clues toward development of safer immune checkpoint therapies. In addition, we observed a significantly higher rate of pneumonitis in treatment naive
Acknowledgments
Author contributions: A. V. H., P. M., J. S., N. A. P., and V. V. contributed to conception and design. V. V. accepts official responsibility for the overall integrity of the manuscript and ensures all statements in the manuscript are true to his knowledge. M. K., S. R., and V. P. contributed to provision of study materials or patients. M. K., S. R., and V. P. contributed to collection and assembly of data. V. P. and A. V. H. contributed to data analysis and interpretation. M. K., S. R., V. P.,
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FUNDING/SUPPORT: The authors have reported to CHEST that no funding was received for this study.