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Journal of Cancer Research and Clinical Oncology

, Volume 145, Issue 2, pp 479–485 | Cite as

Impact of immune-related adverse events on survival in patients with advanced non-small cell lung cancer treated with nivolumab: long-term outcomes from a multi-institutional analysis

  • Biagio RicciutiEmail author
  • Carlo Genova
  • Andrea De Giglio
  • Maria Bassanelli
  • Maria Giovanna Dal Bello
  • Giulio Metro
  • Marta Brambilla
  • Sara Baglivo
  • Francesco Grossi
  • Rita Chiari
Original Article – Clinical Oncology
  • 259 Downloads

Abstract

Purpose

Immune-checkpoint inhibitors (ICIs) represent the standard of care for platinum-pretreated advanced non-small cell lung cancer patients. Patients treated with ICIs may experience immune-related adverse events (irAEs), that might reflect antitumor responses. Here we evaluated nivolumab efficacy according to the development of irAEs.

Methods

We conducted a multicenter retrospective study of patients with advanced NSCLC treated with nivolumab between October 2013 and September 2017. IrAEs were defined as AEs having immunological basis that required intensive monitoring and interventions.

Results

Among 195 patients [median (range) age, 63 (30–84) years; 128 men (65.6%), 67 women (34.4%)], irAEs were observed in 85 patients (43.6%), including 15 patients (7.6%) with grade 3 or 4 events. Median PFS was 5.7 months in irAEs group compared to 2.0 months of no-irAEs group [HR: 0.41 (95% CI 0.3–0.57), P < 0.0001]. Median OS was 17.8 months compared to 4.0 months of no-irAEs group [HR: 0.33 (95% CI 0.23–0.47), P < 0.0001]. IrAEs were significantly associated with improved clinical outcome in 12- and 6-week landmark analysis. Patients who developed ≥ 2 irAEs during treatment (n: 37) had a significantly longer median PFS and OS compared to those with one (n: 48) or none AEs (n: 110) (PFS: 8.5 months vs. 4.6 vs. 2.0, P < 0.0001; OS: 26.8 months vs. 11.9 vs. 4.0, P < 0.0001). Multivariable analysis revealed that irAEs were positively associated with PFS [HR: 0.48 (95% CI 0.34–0.67), P < 0.0001] and OS [HR: 0.38 (95% CI 0.26–0.56), P < 0.0001].

Conclusion

In this study we confirmed that the development of irAEs was a strong predictor of survival outcomes in NSCLC patients treated with nivolumab monotherapy in landmark and multivariable models. Patients who experienced ≥ 2 irAEs had a more pronounced survival benefit compared to those with 1 irAE further suggesting a mechanistic association between irAEs and immunotherapy efficacy.

Keywords

Immune-related AEs Non-small cell lung cancer Nivolumab 

Notes

Acknowledgements

This work was selected as Poster Presentation at 2018 American Society of Clinical Oncology (ASCO) Annual Meeting (Chicago, 2018) and as Oral Presentation at World Conference on Lung Cancer (WCLC) (Toronto, 2018).

Compliance with ethical standards

Ethical approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

Informed consent

Informed consent was obtained from all individual participants included in the study.

Conflict of interest

The authors have no conflict of interest to disclose.

Supplementary material

432_2018_2805_MOESM1_ESM.pdf (35 kb)
Supplementary material 1 (PDF 34 KB)
432_2018_2805_MOESM2_ESM.pdf (10 kb)
Supplementary material 2 (PDF 10 KB)

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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2018

Authors and Affiliations

  • Biagio Ricciuti
    • 1
    • 4
    Email author
  • Carlo Genova
    • 2
  • Andrea De Giglio
    • 1
  • Maria Bassanelli
    • 3
  • Maria Giovanna Dal Bello
    • 2
  • Giulio Metro
    • 1
  • Marta Brambilla
    • 1
  • Sara Baglivo
    • 1
  • Francesco Grossi
    • 2
  • Rita Chiari
    • 1
  1. 1.Medical OncologySanta Maria della Misericordia HospitalPerugiaItaly
  2. 2.Lung Cancer UnitOspedale Policlinico San MartinoGenoaItaly
  3. 3.Medical OncologySan Camillo de Lellis HospitalRietiItaly
  4. 4.Medical OncologySanta Maria della Misericordia Hospital, Azienda Ospedaliera di PerugiaPerugiaItaly

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