Gender Difference in sidE eFfects of ImmuNotherapy: a possible clue to optimize cancEr tReatment (G-DEFINER): study protocol of an observational prospective multicenter study

Authors

  • Rosalba Miceli Unit of Biostatistics for Clinical Research, Department of Epidemiology and Data Science, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy
  • Hanna Eriksson Department of Oncology-Pathology, Karolinska Institutet, Stockholm, Sweden; Theme Cancer, unit of Head-Neck-, Lung-, and Skin Cancer Karolinska University Hospital-Solna, Stockholm, Sweden
  • Giuseppe Lo Russo Thoracic Oncology Unit, Medical Oncology Department, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy
  • Salvatore Alfieri Head and Neck Unit, Medical Oncology Department, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy
  • Maria Moksnes Bjaanæs Department of Oncology, Oslo University Hospital, Oslo, Norway
  • Filippo Pietrantonio Medical Oncology Department, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy
  • Loris De Cecco Integrated biology of rare tumors, Department of Experimental Oncology, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy
  • Arsela Prelaj Thoracic Oncology Unit, Medical Oncology Department, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy
  • Claudia Proto Thoracic Oncology Unit, Medical Oncology Department, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy
  • Johan Franzén Department of Oncology-Pathology, Karolinska Institutet, Stockholm, Sweden; Theme Cancer, unit of Head-Neck-, Lung-, and Skin Cancer Karolinska University Hospital-Solna, Stockholm, Sweden
  • Deirdre McDonnell Department of Medical Oncology, St Vincent’s University Hospital, Dublin, Ireland
  • José Javier Berenguer Pina Department of Medical Oncology, St Vincent’s University Hospital, Dublin, Ireland
  • Teresa Beninato Thoracic Oncology Unit, Medical Oncology Department, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy
  • Laura Mazzeo Thoracic Oncology Unit, Medical Oncology Department, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy
  • Patrizia Giannatempo Medical Oncology Department, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy
  • Elena Verzoni Medical Oncology Department, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy
  • John Crown Department of Medical Oncology, St Vincent’s University Hospital, Dublin, Ireland
  • Åslaug Helland Radium Hospital/Oncology, University of Oslo, Institute of Clinical medicine, Oslo, Norway
  • Alexander Eustace Department of Medical Oncology, St Vincent’s University Hospital, Dublin, Ireland

DOI:

https://doi.org/10.2340/1651-226X.2024.24179

Keywords:

Cancer, Immune checkpoint inhibitors, Immune related adverse events, Sex- and gender differences, Prospective trial

Abstract

Background: Immune checkpoint inhibitors (ICIs) have significantly improved outcomes in various cancers. ICI treatment is associated with the incidence of immune-related adverse events (irAEs) which can affect any organ. Data on irAEs occurrence in relation to sex- differentiation and their association with gender-specific factors are limited.

Aims: The primary objective of the G-DEFINER study is to compare the irAEs incidence in female and male patients who undergo ICI treatment. Secondary objectives are: to compare the irAEs incidence in pre- and postmenopausal female patients; to compare the irAEs incidence in female and male patients according to different clinical and gender-related factors (lifestyle, psychosocial, and behavioral factors). Exploratory objectives of the study are to compare and contrast hormonal, gene-expression, SNPs, cytokines, and gut microbiota profiles in relation to irAEs incidence in female and male patients.

Methods and Results: The patients are recruited from Fondazione IRCCS Istituto Nazionale dei Tumori, Italy, St Vincent’s University Hospital, Ireland, Oslo University Hospital, Norway, and Karolinska Insitutet/Karolinska University Hospital, Sweden. The inclusion of patients was delayed due to the Covid pandemic, leading to a total of 250 patients recruited versus a planned number of 400 patients. Clinical and translational data will be analyzed.

Interpretation: The expected outcomes are to improve the management of cancer patients treated with ICIs, leading to more personalized clinical approaches that consider potential toxicity profiles. The real world nature of the trial makes it highly applicable for timely irAEs diagnosis.

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Author Biographies

Hanna Eriksson, Department of Oncology-Pathology, Karolinska Institutet, Stockholm, Sweden; Theme Cancer, unit of Head-Neck-, Lung-, and Skin Cancer Karolinska University Hospital-Solna, Stockholm, Sweden

Shared first author

Åslaug Helland, Radium Hospital/Oncology, University of Oslo, Institute of Clinical medicine, Oslo, Norway

Shared last author

Alexander Eustace, Department of Medical Oncology, St Vincent’s University Hospital, Dublin, Ireland

Shared last author

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Published

2024-04-21

How to Cite

Miceli, R., Eriksson, H., Lo Russo, G., Alfieri, S., Moksnes Bjaanæs, M., Pietrantonio, F., … Eustace, A. (2024). Gender Difference in sidE eFfects of ImmuNotherapy: a possible clue to optimize cancEr tReatment (G-DEFINER): study protocol of an observational prospective multicenter study. Acta Oncologica, 63(1), 213–219. https://doi.org/10.2340/1651-226X.2024.24179