Risk of Pneumonitis Associated with Programmed Cell Death 1 Inhibitors in Cancer Patients: A Meta-analysis

Pneumonitis, a rare but potentially life-threatening adverse event in cancer patients receiving programmed death 1 (PD-1) or programmed death ligand 1 (PD-L1) inhibitors, has been reported in case reports, clinical trials, and retrospective studies. We performed a systematic review and meta-analysis to calculate the RR of pneumonitis associated with the use of PD-1/L1 inhibitors in randomized clinical trials (RCT). We searched MEDLINE, Embase, the Cochrane Central Register of Controlled Trials, trial registers, conference proceedings, review articles, and reference lists of trial publications for all relevant RCTs comparing PD-1/L1 inhibitors to control with available data on pneumonitis. The pooled incidence, RR, and 95% confidence intervals (CI) were calculated using fixed effects or random effects model according to the heterogeneity of included trials. Twelve RCTs were eligible for the meta-analysis, yielding a total of 5,775 patients included in trials evaluating a PD-1 inhibitor; no eligible trials evaluated a PD-L1 inhibitor. The pooled incidence of all-grade pneumonitis for patients treated with PD-1 inhibitors was 3.2% (95% CI, 2.3-4.5), and that of high-grade pneumonitis was 1.1% (95% CI, 0.7-1.7). The RR of all-grade and high-grade pneumonitis was 4.36 (95% CI, 2.58-7.38) and 2.86 (95% CI, 1.30-6.31), respectively. In a sensitivity analysis, PD-1 inhibitors were also associated with significantly increased risk of pneumonitis per person-month (for all grade, RR = 3.37; 95% CI, 1.97-5.76; for high grade, RR = 2.25; 95% CI, 1.03-4.94). PD-1 inhibitors were associated with a significant increase of all-grade and high-grade pneumonitis both per treatment episode and per person-month. (C)2017 AACR.