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.

Aged Antineoplastic Agents, Immunological / adverse effects Carcinoma, Non-Small-Cell Lung / drug therapy Drug-Related Side Effects and Adverse Reactions / epidemiology Female Follow-Up Studies Humans Lung Neoplasms / drug therapy Male Meta-Analysis as Topic Nivolumab / adverse effects Prognosis Retrospective Studies Survival Rate Withholding Treatment
ICI discontinuation Immune checkpoint inhibition Immune-related adverse events Nivolumab Pneumonitis

Journal

Cancer immunology, immunotherapy : CII
ISSN: 1432-0851
Titre abrégé: Cancer Immunol Immunother
Pays: Germany
ID NLM: 8605732

Informations de publication

Date de publication:
Jul 2020
Historique:
received: 12 08 2019
accepted: 24 02 2020
pubmed: 7 3 2020
medline: 1 7 2020
entrez: 7 3 2020
Statut: ppublish

Résumé

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. 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. 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. 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.

Sections du résumé

BACKGROUND 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 OBJECTIVE
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 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 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.

Identifiants

DOI: 10.1007/s00262-020-02536-5 PMID: 32140762
pubmed: 32140762
doi: 10.1007/s00262-020-02536-5
pii: 10.1007/s00262-020-02536-5
doi:

Substances chimiques

Antineoplastic Agents, Immunological 0
Nivolumab 31YO63LBSN

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

1177-1187

Commentaires et corrections

Type : ErratumIn

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Auteurs

Abdul Rafeh Naqash (AR)

Division of Cancer Treatment and Diagnosis, Developmental Therapeutics Clinic, National Cancer Institute, Bldg 31/3A44, 31 Centre Drive, Bethesda, MD, 20892, USA. abdulrafeh.naqash@nih.gov.
Division of Hematology/Oncology, Department of Internal Medicine, East Carolina University, Greenville, NC, USA. abdulrafeh.naqash@nih.gov.

Biagio Ricciuti (B)

Thoracic Oncology Unit, Santa Maria Della Misericordia Hospital, University of Perugia, Perugia, Italy.
Lowe Center for Thoracic Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.

Dwight H Owen (DH)

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

Vaia Florou (V)

Division of Oncology, Department of Medicine, University of Miami Miller School of Medicine, Miami, FL, USA.
Division of Medical Oncology, Huntsman Cancer Institute, University of Utah, Salt Lake City, UT, USA.

Yukihiro Toi (Y)

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

Cynthia Cherry (C)

Division of Cancer Treatment and Diagnosis, Developmental Therapeutics Clinic, National Cancer Institute, Bldg 31/3A44, 31 Centre Drive, Bethesda, MD, 20892, USA.
Division of Hematology/Oncology, Department of Internal Medicine, East Carolina University, Greenville, NC, USA.

Maida Hafiz (M)

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

Andrea De Giglio (A)

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

Mavish Muzaffar (M)

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

Sandip H Patel (SH)

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

Shunichi Sugawara (S)

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

Jarred Burkart (J)

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

Wungki Park (W)

Division of Oncology, Department of Medicine, University of Miami Miller School of Medicine, Miami, FL, USA.
Memorial Sloan Kettering Cancer Center, New York, USA.

Rita Chiari (R)

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

Jun Sugisaka (J)

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

Gregory A Otterson (GA)

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

Gilberto de Lima Lopes (G)

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

Paul R Walker (PR)

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

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