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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

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A Correction to this article was published on 28 April 2020

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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.

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Data availability

The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request.

Change history

  • 28 April 2020

    The original version of this article unfortunately contained a mistake. The second sentence of the section “irAEs and ICI efficacy” should read as.

Abbreviations

CTLA-4:

Cytotoxic T-lymphocyte-associated protein-4

ECOG:

Eastern cooperate oncology group

G:

Grade

ICI:

Immune checkpoint inhibitors

IrAE:

Immune-related adverse events

OS:

Overall survival

PD-1:

Programmed cell death-1

PFS:

Progression-free survival

PS:

Performance status

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Acknowledgements

We thank the contributing centers as well as ECU IRB. We also thank the clinical research coordinators from ECU (Ms. Sue Ann Joyner and Ms. Susan Eubanks) for facilitating data sharing.

Funding

No relevant funding was required in conducting this study.

Author information

Authors and Affiliations

  1. Division of Cancer Treatment and Diagnosis, Developmental Therapeutics Clinic, National Cancer Institute, Bldg 31/3A44, 31 Centre Drive, Bethesda, MD, 20892, USA

    Abdul Rafeh Naqash & Cynthia Cherry

  2. Thoracic Oncology Unit, Santa Maria Della Misericordia Hospital, University of Perugia, Perugia, Italy

    Biagio Ricciuti, Andrea De Giglio & Rita Chiari

  3. Lowe Center for Thoracic Oncology, Dana-Farber Cancer Institute, Boston, MA, USA

    Biagio Ricciuti

  4. Division of Medical Oncology, Department of Internal Medicine, Ohio State University, Columbus, OH, USA

    Dwight H. Owen, Sandip H. Patel, Jarred Burkart & Gregory A. Otterson

  5. Division of Oncology, Department of Medicine, University of Miami Miller School of Medicine, Miami, FL, USA

    Vaia Florou, Wungki Park & Gilberto de Lima Lopes

  6. Department of Pulmonary Medicine, Sendai Kousei Hospital, Hirosemachi, Aoba-Ku, Sendai, Japan

    Yukihiro Toi, Shunichi Sugawara & Jun Sugisaka

  7. Division of Hematology/Oncology, Department of Internal Medicine, East Carolina University, Greenville, NC, USA

    Abdul Rafeh Naqash, Cynthia Cherry, Mavish Muzaffar & Paul R. Walker

  8. Department of Pulmonary Medicine, East Carolina University, Greenville, NC, USA

    Maida Hafiz

  9. Memorial Sloan Kettering Cancer Center, New York, USA

    Wungki Park

  10. Division of Medical Oncology, Huntsman Cancer Institute, University of Utah, Salt Lake City, UT, USA

    Vaia Florou

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  1. Abdul Rafeh Naqash
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Contributions

ARN was involved in the acquisition, analysis, interpretation of data acquired from all institutions and drafting of the manuscript. ARN, CC, and MH were involved in the clinical annotation of data from East Carolina University. BR was involved in assisting in some aspects of the conceptual design of the study and data interpretation. BR, DHO, and VF were involved in critical revisions of the manuscript content. BR, AG, YT, JS, DHO, SKP, JB, VF, and WP were involved in collection of patient data from respective institutions. GAO, RC, SS, GDLL, CC, and PW were involved in the clinical care of patients from respective institutions. MM and GAO assisted in revising the manuscript drafts. ARN had full access to data from all participating institutions and assumes full responsibility for the integrity and accuracy of the analysis. All authors had access and approved the final version of the manuscript.

Corresponding author

Correspondence to Abdul Rafeh Naqash.

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Conflict of interest

The authors declare they have no potential conflicts of interest directly or indirectly relevant to the conduct or analysis of this study.

Ethical approval

The primary IRB approval was obtained from East Carolina Univ IRB (UMCIRB 15-001400). All participating centers had secured their respective IRB approval to collect their institutional data. To permit the sharing of de-identified data, a data use agreement was signed between ECU and the outside institution providing de-identified data. Patient consent was not required as part of the IRB approved studies since no identifiable information was shared or used for analysis or publication. All this was done in accordance with the regulations covered by the respective institutional IRBs.

Informed consent

No identifiable patient information has been published warranting individual consent from patients. The requirement for individual patient informed consent for the purpose of data collection and publication was waived as per the regulations covered under the respective institutional IRBs (East Carolina Univ, Ohio State Univ, Sendai Kousei Hospital, Univ of Perugia, University of Miami).

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Naqash, A.R., Ricciuti, B., Owen, D.H. et al. 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. Cancer Immunol Immunother 69, 1177–1187 (2020). https://doi.org/10.1007/s00262-020-02536-5

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