The effect of adding immune checkpoint inhibitors on the risk of pneumonitis for solid tumours: a meta-analysis of phase III randomised controlled trials

Background: Immune checkpoint inhibitors (ICIs) have become one of the standard treatment options for solid tumours; however, treatment-related adverse events, including pneumonitis, sometimes disrupt the ongoing treatment. To evaluate the impact of ICI addition on the risk of pneumonitis, a meta-analysis was conducted. Methods: Phase III randomised controlled trials comparing ICIs and conventional therapy with conventional therapy alone were selected by searching databases, including PubMed, Embase, Web of Science and Cochrane Library. The odds ratio (OR) of any grade and grade III–V pneumonitis was calculated. Meta-analysis was performed to compare the incidence of pneumonitis between the treatment arm with additional ICIs and the arm with conventional therapy. Results: A total of 25 randomised controlled trials (RCTs) representing 16,343 patients for grade I–V and 23 RCTs with 15,006 patients for grade III–V pneumonitis were analysed. Adding ICIs was associated with a significant increase in pneumonitis (grade I–V: OR, 2.67, 95% confidence interval [CI]: 2.12–3.37, grade III–V: OR, 1.83, 95% CI: 1.26–2.65). In subgroup analyses based on the mechanism of action of ICIs, cancer types (lung and non-lung cancer) and each ICI, no significant difference in heterogeneity was observed. Conclusions: Adding ICIs to the conventional treatment for solid tumours significantly increased both grade I–V and grade III–V pneumonitis regardless of the mechanisms of ICIs and cancer type. These results would be helpful for oncologists to choose the appropriate treatment options using ICIs, particularly for patients with known risk factors of pneumonitis or interstitial lung disease.