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Meta-Analysis
. 2016 Jun;10(3):183-93.
doi: 10.1177/1753465816636557. Epub 2016 Mar 4.

Risk of pneumonitis in cancer patients treated with immune checkpoint inhibitors: a meta-analysis

Omar Abdel-Rahman  1 , Mona Fouad  2
Affiliations
Meta-Analysis

Risk of pneumonitis in cancer patients treated with immune checkpoint inhibitors: a meta-analysis

Omar Abdel-Rahman et al. Ther Adv Respir Dis. 2016 Jun.

Abstract

Background: A meta-analysis of the risk of pneumonitis associated with the use of immune checkpoint inhibitors in cancer patients has been conducted.

Methods: Eligible publications included randomized trials of cancer patients on immune checkpoint inhibitors, describing events of all-grade and high-grade pneumonitis.

Results: After exclusion of noneligible citations, a total of 11 clinical trials were eligible for the meta-analysis. The odds ratio was 3.96 [95% confidence interval (CI): 2.02-7.79; p < 0.0001] for all-grade pneumonitis and 2.87 (95% CI: 0.90-9.20; p = 0.08) for high-grade pneumonitis. Moreover, the odds ratio of all-grade pneumonitis with a nivolumab/ipilimumab combination versus ipilimumab monotherapy was 3.68 (95% CI: 1.59-8.50; p = 0.002) and, for high-grade pneumonitis, it was 1.86(95% CI: 0.36-9.53; p = 0.46). Subgroup analysis did not reveal a difference between lung cancer patients and other cancer patients in the risk of pneumonitis.

Conclusions: Our analysis provided evidence that the use of immune checkpoint inhibitors is associated with an increased risk of all-grade pneumonitis compared with chemotherapy or placebo controls.

Keywords: NSCLC; ipilimumab; nivolumab; pembrolizumab; pneumonitis.

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Conflict of interest statement

Conflict of interest statement: The authors declare no conflicts of interest in preparing this article.

Figures

Figure 1.
Figure 1.
Flowchart of study selection procedure.
Figure 2.
Figure 2.
Forest plot for odds ratio of (a) all-grade and (b) high-grade pneumonitis for cancer patients receiving immune checkpoint inhibitors compared with control. CI, confidence interval; df, degrees of freedom; M-H, Mantel–Haenszel; NSCLC, non-small cell lung cancer. (Robert 2015a)
Figure 3.
Figure 3.
Forest plot for odds ratio of (a) all-grade and (b) high-grade pneumonitis for cancer patients receiving a nivolumab/ipilimumab combination compared with ipilimumab monotherapy. CI, confidence interval; df, degrees of freedom; M-H, Mantel–Haenszel.
Figure 4.
Figure 4.
Forest plot for OR of (a) all-grade; and (b) high-grade pneumonitis for cancer patients receiving PD-1 inhibitors compared to ipilimumab monotherapy. CI, confidence interval; df, degrees of freedom; M-H, Mantel–Haenszel. (Robert 2015b)
Figure 5.
Figure 5.
Forest plot for publication bias. OR, odds ratio; SE, standard error.
See this image and copyright information in PMC

References

    1. Abdel-Rahman O. (2016) Immune checkpoints aberrations and gastric cancer; assessment of prognostic value and evaluation of therapeutic potentials. Crit Rev Oncol Hematol 97: 65–71. - PubMed
    1. Abdel-Rahman O., ElHalawani H. (2015d) Risk of fatal pulmonary events in patients with advanced non-small-cell lung cancer treated with EGF receptor tyrosine kinase inhibitors: a comparative meta-analysis. Future Oncol 11: 1109–1122. - PubMed
    1. Abdel-Rahman O., ElHalawani H., Fouad M. (2015a) Risk of gastrointestinal complications in cancer patients treated with immune checkpoint inhibitors: a meta-analysis. Immunotherapy 7: 1213–1227. - PubMed
    1. Abdel-Rahman O., ElHalawani H., Fouad M. (2015b) Risk of cutaneous toxicities in patients with solid tumors treated with immune checkpoint inhibitors: a meta-analysis. Future Oncol 11: 2471–2484. - PubMed
    1. Abdel-Rahman O., ElHalawani H., Fouad M. (2015c) Risk of elevated transaminases in cancer patients treated with immune checkpoint inhibitors: a meta-analysis. Expert Opin Drug Saf 14: 1507–1518. - PubMed

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