OA21.01 Pooled Analysis of the Incidence and Risk of Treatment-Related Pneumonitis with Anti-PD-1/PD-L1 Therapies in Cancer Patients

Abstract

Blockade of programmed death 1 (PD-1), or its ligand, PD-L1, could restore T-cell immunity. Anti-PD-1/ or anti-PD-L1 antibodies have demonstrated promising efficacy in the treatment of cancer patients. The toxicity spectrum of PD-1/PD-L1 blockers is distinct from chemotherapy or other target agents. Pneumonitis is one of the major side effects of these drugs, and reported incidences vary substantially between clinical trials. We tried to investigate the overall incidence and risk of treatment-related pneumonitis with anti-PD-1/PD-L1 therapies in cancer patients. A systematic search of literature up to January 2016 was performed in EDLINE, EMBASE, and Cochrane databases to identify relevant clinical trials. Paired reviewers independently selected articles for inclusion and extracted data. Incidence and relative risk (RR) of hypertension were calculated using a random-effects or fixed effects model, depending on the heterogeneity of the included studies. A total of 23 clinical trials with 5333 patients were included. The overall incidence of all- and high-grade pneumonitis in cancer patients receiving anti-PD-1/PD-L1 therapies were 3.5% (95% CI, 2.9% to 4.3%) and 1.3% (95% CI, 1.1% to 1.9%), respectively. Anti-PD-1/PD-L1 antibodies were associated with a significantly increased risk of all-grade pneumonitis in patients with cancer with an RR of 5.47 (95% CI, 2.17 to 13.81; p<0.001) compared with controls. The risk of high-grade pneumonitis was also increased with the use of anti-PD-1/PD-L1 antibodies, though not statistically significant (RR 3.86; 95% CI 0.98 to 15.22; p=0.054). Patients with cancer receiving anti-PD-1/PD-L1 therapies have a significant risk of developing pneumonitis. Early and appropriate management is strongly recommended to avoid unnecessary dose reductions and transitory or definitive treatment discontinuations due to pneumonitis.