Prognostic Significance of the Severity of Immune-Related Adverse Events in Advanced Cancer Patients Treated with PD-1/PD-L1 Inhibitors: A Real-World Data Analysis

Target Oncol. 2023 Jan;18(1):147-158. doi: 10.1007/s11523-022-00936-4. Epub 2022 Dec 14.

Abstract

Background: There is limited evidence regarding immune-related adverse events (irAEs) in Asian cancer patients treated with antibodies directed against programmed cell death-1 (PD-1) or programmed cell death-ligand 1 (PD-L1).

Objective: This study aimed to investigate the clinical patterns and prognostic significance of grade 1-2 and grade ≥ 3 irAEs by PD-1/PD-L1 inhibitors in cancer patients using real-world clinical data.

Patients and methods: We conducted a retrospective study of cancer patients who received pembrolizumab, nivolumab, or atezolizumab at a tertiary hospital in South Korea. Incidence, time to onset, and grade 1-2 and grade ≥ 3 irAE risk factors were analyzed from medical records. The association of irAE severity with progression-free survival (PFS) and prognostic factors for PFS were evaluated.

Results: Among a total of 431 patients, irAEs occurred in 45.2%, and 9.5% were grade ≥ 3 irAEs. There were no significant differences in the median time to onset based on severity. Risk factors for the development of grade ≥ 3 irAEs were the presence of autoimmune disorders or diabetes mellitus. The median PFS was significantly different at 13.20, 9.00 and 4.17 months for the grade 1-2, grade ≥ 3, and no irAE groups, respectively. An increase in administration cycles was associated with a reduced risk of progression in patients with grade 1-2 and grade ≥ 3 irAEs.

Conclusions: The development of grade ≥ 3 irAEs was affected by comorbidities and associated with improved PFS compared with those without irAEs. Our findings identified the real-world epidemiology, risk factors, and prognostic significance of irAEs, which may guide treatment decisions of PD-1/PD-L1 inhibitors.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents, Immunological* / adverse effects
  • Data Analysis
  • Humans
  • Immune Checkpoint Inhibitors* / adverse effects
  • Lung Neoplasms* / drug therapy
  • Neoplasms* / drug therapy
  • Prognosis
  • Programmed Cell Death 1 Receptor
  • Retrospective Studies

Substances

  • Antineoplastic Agents, Immunological
  • Immune Checkpoint Inhibitors
  • Programmed Cell Death 1 Receptor