Outcomes associated with immune-related adverse events in metastatic non-small cell lung cancer treated with nivolumab: a pooled exploratory analysis from a global cohort

Abdul Rafeh Naqash, Biagio Ricciuti, Dwight H. Owen, Vaia Florou, Yukihiro Toi, Cynthia Cherry, Maida Hafiz, Andrea De Giglio, Mavish Muzaffar, Sandip H. Patel, Shunichi Sugawara, Jarred Burkart, Wungki Park, Rita Chiari, Jun Sugisaka, Gregory A. Otterson, Gilberto de Lima Lopes, Paul R. Walker

Research output: Contribution to journalArticlepeer-review

30 Scopus citations

Abstract

Background: Immune-related adverse events (irAEs) comprise a distinct spectrum of auto-inflammatory manifestations triggered due to immune checkpoint inhibitors (ICI). Current data on the association of irAEs with outcomes in NSCLC treated with nivolumab are limited. Methods and objectives: We pooled data from 531 metastatic NSCLC patients from five centers treated with nivolumab after failing platinum-based chemotherapy. The primary objective was to investigate the relationship between irAEs with clinical benefit to nivolumab as well as to elucidate patterns of irAE-related ICI discontinuations and their impact on survival. Results: 33.0% (173/531) of patients treated with nivolumab were noted to have an irAE. Patients with irAEs had a significantly longer median PFS [6.1 vs. 3.1 months, HR 0.68 95% CI (0.55–0.85); p = 0.001] and OS [14.9 vs. 7.4 months, HR 0.66 95% CI (0.52–0.82); p < 0.001)] compared to those without irAEs. In multivariate analysis, the presence of irAEs showed a significantly better PFS [HR 0.69, 95% CI (0.55–0.87); p = 0.002] and a trend for better OS [HR 0.62, 95% CI (0.55–1.03); p = 0.057]. Patients with permanent ICI discontinuation secondary to index irAE had a significantly shorter median PFS [2.3 vs. 6.6 months, HR 1.74 95% CI (1.06–2.80); p = 0.02] and median OS [3.6 vs. 17.6 months; HR 2.61 95% CI (1.61–4.21); p < 0.001] compared to those that did not have permanent ICI discontinuation. Conclusions: Our pooled exploratory analysis demonstrates improved clinical benefit to nivolumab in NSCLC patients experiencing irAEs. We also observed negative impact of irAE-related treatment discontinuation on survival in this group of patients.

Original languageEnglish (US)
Pages (from-to)1177-1187
Number of pages11
JournalCancer Immunology, Immunotherapy
Volume69
Issue number7
DOIs
StatePublished - Jul 1 2020

Keywords

  • ICI discontinuation
  • Immune checkpoint inhibition
  • Immune-related adverse events
  • Nivolumab
  • Pneumonitis

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Oncology
  • Cancer Research

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