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Endocrine toxicity in cancer patients treated with nivolumab or pembrolizumab: results of a large multicentre study

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Abstract

Introduction

The immune checkpoint inhibitors (ICPIs) agents anti-T lymphocytes-associated antigen 4 (CTLA-4) and anti-programmed cell death protein-1 (PD-1) and its ligands (PD-L1/PD-L2) have opened a new scenario in the treatment of cancer. These agents can induce immuno-related adverse events (irAEs), which may affect the endocrine system.

Purpose

The aim of this study was to analyze the occurrence and the course of endocrine irAEs in cancer patients treated with anti-PD-1 immunotherapy.

Methods

This was a retrospective, multicentre study, involving cancer patients treated with the PD-1 inhibitors nivolumab or pembrolizumab at reference Oncology Centres. One hundred and seventy-nine consecutive patients with different types of cancer (mostly non-small cell lung cancer, melanoma, kidney cancer) were included in the study. Patients had received nivolumab (70.9%) or pembrolizumab (29.1%) for 2–33 months. The study evaluated clinical data records until the established date of July 15, 2018. The primary end point was the assessment of endocrine toxicity and possible predictive factors.

Results

Endocrine toxicity occurred in 54 out of 179 patients (30.2%) and was related to thyroid dysfunction, with the exception of one case of diabetes mellitus. Thyroid toxicity occurred mostly within 2 months from the initiation of immunotherapy (83% of cases). A pre-existing thyroid dysfunction was a significant predictor of disease flare.

Conclusions

Thyroid alterations are frequently associated with anti PD-1 treatment in cancer patients. Regular thyroid assessment should be performed, particularly in the first months of treatment and in patients with a pre-existing thyroid disease.

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Authors and Affiliations

  1. Endocrinology, Department of Experimental and Clinical Biomedical Sciences “Mario Serio”, University of Florence, AOU Careggi, Viale Pieraccini, 6, 50139, Florence, Italy

    E. M. Presotto, M. Maggi & A. Peri

  2. Andrology, Female Endocrinology and Gender Incongruence Unit, Department of Experimental and Clinical Biomedical Sciences “Mario Serio”, University of Florence, AOU Careggi, 50139, Florence, Italy

    G. Rastrelli

  3. Radiation Oncology Unit, Department of Oncology and Experimental Clinical and Biomedical Sciences “Mario Serio”, AOU Careggi, University of Florence, Florence, Italy

    I. Desideri & V. Scotti

  4. Melanoma and Skin Cancer Unit, Tuscany Central District, Department of Health Sciences, Dermatology Unit, University of Florence, Florence, Italy

    S. Gunnella & N. Pimpinelli

  5. Medical Oncology and Immuno-Related Tumors, Centro di Riferimento Oncologico di Aviano (CRO) IRCCS, Aviano, Italy

    E. Vaccher & A. Bearz

  6. Medical Oncology Unit, AOU Careggi, Florence, Italy

    F. Di Costanzo

  7. Unit of Translational Oncology, AOU Careggi, Department of Health Sciences, Section of Clinical Pharmacology and Oncology, University of Florence, Florence, Italy

    M. Bruggia & E. Mini

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  1. E. M. Presotto
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Correspondence to A. Peri.

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Presotto, E.M., Rastrelli, G., Desideri, I. et al. Endocrine toxicity in cancer patients treated with nivolumab or pembrolizumab: results of a large multicentre study. J Endocrinol Invest 43, 337–345 (2020). https://doi.org/10.1007/s40618-019-01112-8

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