PD-1 inhibitors increase the incidence and risk of pneumonitis in cancer patients in a dose-independent manner: a meta-analysis

Sci Rep. 2017 Mar 8;7:44173. doi: 10.1038/srep44173.

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.

Publication types

  • Meta-Analysis
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Antineoplastic Agents / adverse effects*
  • Antineoplastic Agents / therapeutic use
  • Carcinoma, Non-Small-Cell Lung
  • Carcinoma, Renal Cell / drug therapy*
  • Carcinoma, Renal Cell / epidemiology
  • Clinical Trials, Phase II as Topic
  • Clinical Trials, Phase III as Topic
  • Dose-Response Relationship, Drug
  • Female
  • Humans
  • Incidence
  • Kidney Neoplasms / drug therapy*
  • Kidney Neoplasms / epidemiology
  • Lung Neoplasms / drug therapy*
  • Lung Neoplasms / epidemiology
  • Male
  • Pneumonia* / chemically induced
  • Pneumonia* / epidemiology
  • Programmed Cell Death 1 Receptor / antagonists & inhibitors*

Substances

  • Antineoplastic Agents
  • PDCD1 protein, human
  • Programmed Cell Death 1 Receptor