Critical Reviews in Oncology / Hematology 157 (2021) 103176 Available online 17 November 2020 1040-8428/© 2020 Elsevier B.V. All rights reserved. European School of Oncology – Review Palliative- and non-palliative indications for glucocorticoids use in course of immune-checkpoint inhibition. Current evidence and future perspectives Daniele Marinelli a, b, 1 , Raffaele Giusti c, 2 , Marco Mazzotta b , Marco Filetti a, 1 , Eriseld Krasniqi b , Laura Pizzuti b , Lorenza Landi b , Silverio Tomao d , Federico Cappuzzo b , Gennaro Ciliberto e , Maddalena Barba b, *, Patrizia Vici b , Paolo Marchetti a, 3 a Department of Clinical and Molecular Medicine, Sapienza - University of Rome, Sant’Andrea Hospital, Rome, Italy b Division of Medical Oncology 2, IRCCS Regina Elena, National Cancer Institute, Rome, Italy c Medical Oncology Unit, Sant’Andrea Hospital, Rome, Italy d Department of Radiological, Oncological and Anatomo-Pathological Sciences, Policlinico Umberto I, ‘Sapienza’ University of Rome, Rome, Italy e Scientifc Direction, IRCCS Regina Elena, National Cancer Institute, Rome, Italy A R T I C L E INFO Keywords: Cancer Immunotherapy Glucocorticoids Immune-checkpoint blockade Palliative care ABSTRACT Immune-checkpoint inhibitors signifcantly reshaped treatment landscapes in several solid tumors. Concurrently with disease-oriented therapies, cancer patients often require proper management of drug-related adverse events and/or cancer-related symptoms. Glucocorticoids (GC) are a cornerstone of symptom management in advanced cancer care and in the management of immune-related adverse events (irAEs) due to immune-modulating therapies. Moreover, GC are often administered in patients with autoimmune diseases (AID), either alone or in combination with other treatments. While handling of irAEs with GC is supported by multiple guidelines, it is unclear whether GC administration because of pre-existing AID or because of palliative needs is associated with inferior outcomes in cancer patients treated with immune-checkpoint inhibitors (ICIs). When globally consid- ered, the available evidence seems to orient towards less favorable survival outcomes when GC administration is driven by a palliative intent. Conversely, steroid administration for non-palliative intent seems to be associated with stable or negligibly reduced survival outcomes. 1. Introduction Metastatic spread in advanced malignances is associated with cancer-related symptoms, which may signifcantly vary in nature and degree of intensity. Glucocorticoids (GC) administration for palliative care in advanced cancer patients has numerous indications, including dyspnea, pain due to spinal cord compression, nausea and vomiting, cancer-related fatigue, and appetite loss (Kloke and Cherny, 2015; Fal- lon et al., 2018; Roila et al., 2016; Yennurajalingam and Frisbee-Hume, 2013; NCCN Guidelines, 2018; Paulsen et al., 2014). GC use also has a widely recognized role in the management of symptomatic brain me- tastases (and leptomeningeal disease)(Ryken et al., 2010; Le Rhun et al., 2017). In recent years, the introduction in clinical practice of immune- checkpoint inhibitors (ICIs) and the in-depth analysis of tumor and immune system interactions have led to speculations about GC inter- ference with the effcacy of immunomodulatory anticancer therapies. The vast majority of clinical trials of ICIs excluded patients requiring treatment with signifcant doses of GC at the time of enrolment, regardless of the indication (Connell et al., 2017), with the most frequent cut-off value established at a dose of 10 mg/day of prednisone equivalent. Moreover, symptomatic central nervous system (CNS) dis- ease is often considered as an exclusion criterion in randomized clinical trials, thus cutting out a signifcant subset of patients eligible for steroid therapy. At last, autoimmune disorders may co-occur in cancer patients who are eligible for ICI therapy. When focusing on patients with lung cancer diagnosis, in about 14–25 % of them, a concomitant autoimmune disease (AID) is present (Khan and Pruitt, 2016). Furthermore, there is * Corresponding author at: Division of Medical Oncology 2, IRCCS IFO-Regina Elena National Cancer Institute, Via Elio Chianesi 53, 00144 Rome, Italy. E-mail address: maddalena.barba@gmail.com (M. Barba). 1 Dr. Daniele Marinelli and Dr. Marco Filetti are both residents in Medical Oncology at Sapienza University in Rome, Italy. 2 Dr. Raffaele Giusti is a Medical Oncologist at Sant’Andrea Hospital in Rome, Italy. 3 Prof. Paolo Marchetti is Director of Medical Oncology Division at Sant’Andrea Hospital in Rome, Italy. Contents lists available at ScienceDirect Critical Reviews in Oncology / Hematology journal homepage: www.elsevier.com/locate/critrevonc https://doi.org/10.1016/j.critrevonc.2020.103176 Received 19 March 2020; Received in revised form 8 November 2020; Accepted 9 November 2020