title: PD-1 inhibitors increase the incidence and risk of pneumonitis in cancer patients in a dose-independent manner: a meta-analysis.
abstract: Therapies that targeted PD-1 have shown remarkable rates of durable clinical responses in patients with various tumor types. However, the extent and knowledge of pulmonary toxicities associated with PD-1 blockade, mainly manifested as pneumonitis, remains obscure. In this study, a total of 6360 subjects from 16 phase II/III clinical trials were pooled for meta-analysis to evaluate the overall incidence and risk of PD-1 inhibitors-related pneumonitis in cancer patients. The incidence of pneumonitis during anti-PD-1 immunotherapy was 2.92% (95%CI: 2.18-3.90%) for all-grade and 1.53% (95%CI: 1.15-2.04%) for high-grade pneumonitis. Compared with routine chemotherapy, PD-1 inhibitors were associated with a significant increased risk of pneumonitis. Moreover, among the types of tumor treated with PD-1 inhibitors, the melanoma patients have the lowest incidence of pneumonitis, while the non-small cell lung cancer (NSCLC) and renal cell carcinoma (RCC) patients have the highest. Furthermore, no significant differences were detected in the incidences of all- and high-grade pneumonitis between high-dose and low-dose groups of PD-1 inhibitors. In conclusion, PD-1 inhibitors were probably associated with an increased risk of pneumonitis in a dose-independent manner, compared with routine chemotherapeutic agents. The frequency and severity of treatment-mediated pneumonitis was quite different in patients with various tumor types.
authors.affiliation: The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China.
authors.forename: Jiaying
authors.initials: J
authors.lastname: Wu
authors.affiliation: The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China.
authors.forename: Dongsheng
authors.initials: D
authors.lastname: Hong
authors.affiliation: Department of Pharmacology, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, China.
authors.forename: Xiangnan
authors.initials: X
authors.lastname: Zhang
authors.affiliation: The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China.
authors.forename: Xiaoyang
authors.initials: X
authors.lastname: Lu
authors.affiliation: The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Miao
mesh_terms: D000970:Antineoplastic Agents / Q000009:adverse effects* / Q000627:therapeutic use; D002289:Carcinoma, Non-Small-Cell Lung; D002292:Carcinoma, Renal Cell / Q000188:drug therapy* / Q000453:epidemiology; D017322:Clinical Trials, Phase II as Topic; D017326:Clinical Trials, Phase III as Topic; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D015994:Incidence; D007680:Kidney Neoplasms / Q000188:drug therapy* / Q000453:epidemiology; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000453:epidemiology; D008297:Male; D011014:Pneumonia / Q000139:chemically induced / Q000453:epidemiology; D061026:Programmed Cell Death 1 Receptor / Q000037:antagonists & inhibitors*
chemical_list: D000970:Antineoplastic Agents; C105992:PDCD1 protein, human; D061026:Programmed Cell Death 1 Receptor