Pneumonitis With Combined Immune Checkpoint Inhibitors and Chemoradiotherapy in Locally Advanced Non-Small-Cell Lung Cancer: a Systematic Review and Meta-Analysis

Abstract

Aims: This study systematically evaluated cases of pneumonitis following combined immune checkpoint inhibitors (ICI) and chemoradiotherapy (CRT) for locally advanced non-small-cell lung cancer (LA-NSCLC). Methods: Studies from Embase, PubMed and the Cochrane Library on patients with LA-NSCLC who received CRT and ICIs were reviewed. The primary outcomes were rates of all-grade, grade 3–5 and grade 5 pneumonitis. Results: Overall, 35 studies involving 5000 patients were enrolled. The pooled rates of all-grade, grade 3–5 and grade 5 pneumonitis were 33.0% (95% CI: 23.5–42.6), 6.1% (95% CI: 4.7–7.4) and 0.8% (95% CI: 0.3–1.2), respectively, with 7.6% of patients discontinuing ICIs because of pneumonitis. Conclusion: The incidence rates of pneumonitis following combined CRT and ICIs for LA-NSCLC were acceptable. However, the pulmonary toxicity of concurrent CRT and nivolumab plus ipilimumab should be noted.

Plain language summary

Combined immune checkpoint inhibitors (ICI) and chemoradiotherapy (CRT) may cause severe pneumonitis due to overlapped pulmonary toxicity. However, the safety data on pneumonitis are limited to a small number of prospective clinical trials and retrospective studies with limited evidence. Thus we conducted a systematic review of pneumonitis in relation to the combination treatment. A total of 35 studies, involving 5000 patients, were included for the final analysis. The pooled rates of all-grade, grade 3–5 and grade 5 pneumonitis were 33.0, 6.1 and 0.8%, respectively, and 7.6% of patients stopped taking ICIs because of pneumonitis. The pneumonitis rates following combined CRT and ICIs for LA-NSCLC were acceptable, but the pulmonary toxicity of concurrent CRT and nivolumab plus ipilimumab should be noted.

Keywords::

• chemoradiation
• immune checkpoint inhibitors
• locally advanced non-small-cell lung cancer
• pneumonitis

Supplementary data

To view the supplementary data that accompany this paper please visit the journal website at: www.tandfonline.com/doi/suppl/10.2217/fon-2022-1274

Author contributions

All authors contributed to the design of this study and to the drafting of the paper and have seen and approved the final version.

Financial & competing interests disclosure

This research was supported by National Natural Science Foundation of China (grant No. 82172865), Start-up fund of Shandong Cancer Hospital (grant No. 2020-B14), Clinical Research Special Fund of Wu Jieping Medical Foundation (grant Nos. 320.6750.2021-02-51 and 320.6750.2021-17-13). The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.