Clinical difference between discontinuation and retreatment with nivolumab after immune-related adverse events in patients with lung cancer

Cancer Chemother Pharmacol. 2019 Oct;84(4):873-880. doi: 10.1007/s00280-019-03926-y. Epub 2019 Aug 23.

Abstract

Background: After the cessation of immune checkpoint inhibitor (ICI) therapy due to an immune-related adverse event (irAE), it remains unclear whether retreatment with ICI is more effective than its discontinuation. To explore the clinical significance of its retreatment, patients with non-small cell lung cancer (NSCLC) who had treatment interruption of nivolumab due to irAEs were identified and the clinical differences between discontinuation and retreatment with nivolumab were retrospectively reviewed.

Methods: 49 (26%) of 187 patients treated with nivolumab experienced the cessation of treatment due to a serious irAE. Retreatment was chosen in 21 patients (retreatment cohort), while 28 patients discontinued treatment (discontinuation cohort).

Results: The most common irAEs requiring treatment cessation in 49 patients included pneumonitis (59.2%), adrenal insufficiency (8.2%), liver dysfunction (8.2%) renal dysfunction (8.2%), colitis (6.1%), hypothyroidism (4.1%), and rash (2.0%). The frequency of grade 3 or 4 initial irAEs did not differ between the retreatment and discontinuation cohorts; however, the incidence of renal dysfunction and colitis was higher in the retreatment cohort than in the discontinuation cohort. Retreatment with nivolumab displayed an overall response rate of 15%, without a significant increase in irAEs. The median overall survival and progression-free survival did not differ significantly between the retreatment and discontinuation cohorts, irrespective of the efficacy of prior nivolumab.

Conclusions: Retreatment exhibited a slightly higher efficacy without a significant increase in irAEs; however, the clinical significance of retreatment and discontinuation was similar in NSCLC patients that led to treatment interruption due to any irAE after initial nivolumab.

Keywords: Discontinuation; NSCLC; Nivolumab; PD-1 inhibitor; Retreatment; irAE.

MeSH terms

  • Antineoplastic Agents, Immunological / administration & dosage
  • Antineoplastic Agents, Immunological / adverse effects
  • Antineoplastic Agents, Immunological / immunology
  • Carcinoma, Non-Small-Cell Lung* / drug therapy
  • Carcinoma, Non-Small-Cell Lung* / immunology
  • Carcinoma, Non-Small-Cell Lung* / pathology
  • Drug-Related Side Effects and Adverse Reactions* / classification
  • Drug-Related Side Effects and Adverse Reactions* / immunology
  • Drug-Related Side Effects and Adverse Reactions* / therapy
  • Female
  • Humans
  • Lung Neoplasms* / drug therapy
  • Lung Neoplasms* / immunology
  • Lung Neoplasms* / pathology
  • Male
  • Middle Aged
  • Nivolumab* / administration & dosage
  • Nivolumab* / adverse effects
  • Nivolumab* / immunology
  • Outcome and Process Assessment, Health Care
  • Programmed Cell Death 1 Receptor / antagonists & inhibitors*
  • Retreatment* / methods
  • Retreatment* / statistics & numerical data
  • Treatment Outcome
  • Withholding Treatment / statistics & numerical data*

Substances

  • Antineoplastic Agents, Immunological
  • Programmed Cell Death 1 Receptor
  • Nivolumab