Effect of Sequence of Radiotherapy Combined With Immunotherapy on the Incidence of Pneumonitis in Patients With Lung Cancer: A Systematic Review and Network Meta-Analysis

Clin Lung Cancer. 2024 Jan;25(1):18-28.e3. doi: 10.1016/j.cllc.2023.08.008. Epub 2023 Aug 6.

Abstract

Background: With the widespread application of immune checkpoint inhibitor (ICI) combined with radiotherapy (RT) for the treatment of lung cancer, increasing attention has been paid to treatment-related pneumonitis. The effect of the treatment sequence on the incidence of pneumonitis remains unclear.

Methods: We searched databases including PubMed, Embase, and ClinicalTrials.gov, meeting abstracts, and reference lists of relevant review articles for literature published on radio- and immunotherapy in lung cancer. Stata software (version 16.0) was used for meta-analysis. Data on the incidence of any grade and ≥ grade 3 pneumonitis was pooled using the random effects model. Bayesian network meta-analysis was used for arm-based pairwise comparisons. Subgroup analyses were performed to identify the potential influencing factors.

Results: Thirty-eight studies met our inclusion criteria. The network meta-analysis showed no significant difference between the incidence of pneumonitis in concurrent ICI with RT (concurrent arm) and RT followed by ICI (RT-first arm) (odds ratio [OR]: 0.71, 95% confidence interval [CI]: 0.10-4.81). In the meta-analysis of single group rates, RT following ICI (ICI-first arm) exhibited higher incidence of any grade pneumonitis compared with concurrent- and RT-first arms, with 0.321 (95% CI: 0.260-0.386) for programmed cell death protein 1 (PD-1) inhibitors from clinical trials, and 0.480 (95% CI: 0.363-0.598) for PD-1 inhibitors from real-world retrospective data, respectively.

Conclusion: No significant difference in the incidence of any grade and grade ≥ 3 pneumonitis was found between RT-first and concurrent arms. The ICI-first arm exhibited a higher incidence of pneumonitis, which needs to be further confirmed by follow-up studies.

Keywords: Adverse events (AEs); Clinical trials; Immune checkpoint inhibitor (ICI); RT; Real-world retrospective data; Treatment strategy.

Publication types

  • Meta-Analysis
  • Systematic Review
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Bayes Theorem
  • Humans
  • Immunotherapy / adverse effects
  • Incidence
  • Lung Neoplasms* / drug therapy
  • Lung Neoplasms* / radiotherapy
  • Network Meta-Analysis
  • Pneumonia* / epidemiology
  • Pneumonia* / etiology
  • Retrospective Studies