Incidence risk of PD-1/PD-L1-related pneumonia and diarrhea in non-small cell lung cancer (NSCLC) patients: a systematic review and meta-analysis of randomized controlled trials

Eur J Clin Pharmacol. 2021 Aug;77(8):1079-1088. doi: 10.1007/s00228-020-03083-9. Epub 2021 Feb 10.

Abstract

Background: Programmed cell death-1 (PD-1) and programmed cell death ligand-1(PD-L1) inhibitor therapy have been approved for the treatment of many cancers, although their incidence of some side effects was high. We aim to fully investigate the incidence risk of PD-1/PD-L1 inhibitors-related pneumonia and diarrhea in NSCLC patients, as well as treatment-related deaths.

Methods: PubMed, Medline, Cochrane Library, and Clinical trials.gov databases were searched up to Sep 17, 2020, for clinical trials of PD-1 inhibitors and PD-L1 inhibitors in the treatment of NSCLC. Randomized controlled trials and their references were screened.

Results: Seventeen trials were included in our meta-analysis, including 11,363 patients. PD-1/PD-L1 inhibitors significantly increased the risk of developing all-grade and high-grade (grade ≥ 3) pneumonia (risk ratio [RR] = 2.28; 95% CI: 1.39-3.76; P < 0.01; RR = 2.38; 95% CI: 1.72-3.29; P < 0.01, respectively). The use of PD-1/PD-L1 inhibitor did not increase the risk of developing all-grade and high-grade diarrhea (RR = 0.79; 95% CI: 0.62-1.01; P = 0.06; RR = 0.96; 95% CI: 0.70-1.31; P = 0.78, respectively). There was no significant difference between the rate of death in PD-1 and PD-L1 inhibitors (P = 0.079).

Conclusion: These data suggest that PD-1/PD-L1 inhibitors significantly increase the risk of all-grade and high-grade pneumonia in NSCLC patients and PD-1/PD-L1 monotherapy increases the risk of all-grade pneumonia in NSCLC patients compared to PD-1/PD-L1 inhibitor combination regimens. Physicians should pay more attention to NSCLC patients who treated with PD-1/PD-L1 inhibitors.

Keywords: Diarrhea,; Meta-analysis; NSCLC,; PD-1/PD-L1 inhibitors,; Pneumonia,.

Publication types

  • Meta-Analysis
  • Systematic Review

MeSH terms

  • Antineoplastic Agents / adverse effects*
  • Antineoplastic Agents / therapeutic use
  • B7-H1 Antigen / antagonists & inhibitors*
  • Carcinoma, Non-Small-Cell Lung / drug therapy*
  • Diarrhea / chemically induced
  • Humans
  • Immune Checkpoint Inhibitors / adverse effects*
  • Immune Checkpoint Inhibitors / therapeutic use
  • Incidence
  • Lung Neoplasms / drug therapy*
  • Patient Acuity
  • Pneumonia / chemically induced
  • Randomized Controlled Trials as Topic

Substances

  • Antineoplastic Agents
  • B7-H1 Antigen
  • Immune Checkpoint Inhibitors