Phosphatidylinositol 3 kinase inhibitor-related pneumonitis: a systematic review and meta-analysis

Serious phosphatidylinositol 3 kinase (PI3K) inhibitor-related pneumonitis has raised clinical concerns, and integrated data for this condition are lacking.Randomized controlled trials (RCTs) comparing PI3K inhibitor therapy with control treatments from electronic databases and registrations were searched from inception to 1 April 20231 April 2023seven1 April 2023. The outcomes of our study were the incidence and risk of all-grade and grade ≥ 3 PI3K inhibitor-associated pneumonitis compared with controls.The meta-analysis included 13 studies comprising 3916 patients. The incidence of all-grade and grade ≥ 3 pneumonitis was 3.7% (82/2210) and 3.0% (35/1162) in patients treated with PI3K inhibitors. PI3K inhibitors significantly increased the risk of all-grade and grade ≥ 3 pneumonitis compared with controls (RR 5.63, 95% CI [2.97, 10.65], P < 0.00001; RR 6.85, 95% CI [2.45, 19.11], P = 0.0002, respectively) with no significant heterogeneity across studies. In terms of different PI3K inhibitors, copanlisib and idelalisib significantly increased the risk of pneumonitis compared to controls (RR 4.99, 95% CI [1.19, 21.01], P = 0.03; RR 5.53, 95% CI [2.35, 13.01], P < 0.0001, respectively).PI3K inhibitors significantly increased the risk of pneumonitis compared with controls, and most cases are severe or even life-threatening.CRD42022318878.