Association of Steroids Use with Survival in Patients Treated with Immune Checkpoint Inhibitors: A Systematic Review and Meta-Analysis
Open accessAbstract
Immune checkpoint inhibitors (ICIs) can elicit toxicities by inhibiting negative regulators of adaptive immunity. Sometimes, management of toxicities may require systemic glucocorticoids. We performed a systematic review and meta-analysis of published studies to evaluate the correlation between steroids use, overall survival (OS), and progression-free survival (PFS) in cancer patients treated with ICIs. Publications that compared steroids with non-steroid users in cancer patients treated with ICIs from inception to June 2019 were identified by searching the EMBASE, PubMed, SCOPUS, Web of Science, and Cochrane Library databases. The pooled hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated using a random-effects model. Patients (studies, n = 16; patients, n = 4045) taking steroids were at increased risk of death and progression compared to those not taking steroids (HR = 1.54, 95% CI: 1.24–1.91; p = 0.01 and HR = 1.34, 95% CI: 1.02–1.76; p = 0.03, respectively). The main negative effect on OS was associated with patients taking steroids for supportive care (HR = 2.5, 95% CI 1.41–4.43; p < 0.01) or brain metastases (HR = 1.51, 95% CI 1.22–1.87; p < 0.01). In contrast, steroids used to mitigate adverse events did not negatively affect OS. In conclusion, caution is needed when steroids are used for symptom control. In these patients, a negative impact of steroid use was observed for both OS and PFS.
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A detrimental effect on survival has been suggested when corticosteroids are used for cancer-related symptoms or for the management of a pre-existing autoimmune disease (AID).
“Conversely, a detrimental effect on survival has been suggested when used for cancer-related symptoms or for the management of a pre-existing AID”
From Graves’ Disease during Immune Checkpoint Inhibitor Therapy (A Case Series and Literature Review) (2021) · cites this paper as [62]
The Discussion and Conclusions associate steroids used for cancer-related symptoms with worse survival in patients treated with immune checkpoint inhibitors. But the Introduction says steroids used for cancer-unrelated indications, including autoimmune disease, were not associated with worse outcomes; the paper therefore does not support the autoimmune-disease part of the claim. (LLM, conf=0.90)
Experimental — accuracy not yet measuredHigh-dose steroids can theoretically reverse the anti-cancer benefit of ICPi treatment.
“because high-dose steroids can theoretically reverse the anti-cancer benefit of ICPi treatment [51,62].”
From Graves’ Disease during Immune Checkpoint Inhibitor Therapy (A Case Series and Literature Review) (2021) · cites this paper as [62]
A recent review found that corticosteroids for irAE management seem not to reduce overall survival in cancer patients treated with ICPis.
“A recent review of the literature is reassuring on the use of corticosteroids for irAE management, finding that it seems not to reduce overall survival in cancer patients treated with ICPis [62,63]”
From Graves’ Disease during Immune Checkpoint Inhibitor Therapy (A Case Series and Literature Review) (2021) · cites this paper as [62]
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References 44 · Cited by 300
- Authors
- Petrelli, F., Signorelli, D., Ghidini, M., Ghidini, A., Pizzutilo, E. G., Ruggieri, L., Cabiddu, M., Borgonovo, K., Dognini, G., Brighenti, M., De Toma, A., Rijavec, E., Garassino, M. C., Grossi, F., & Tomasello, G.
- Affiliations
- Azienda Socio Sanitaria Territoriale di Bergamo Ovest (IT)
- Fondazione IRCCS Istituto Nazionale dei Tumori (IT)
- Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico (IT)
- Medical Oncology Unit, Casa di Cura Igea, 20126 Milano, Italy
- Azienda Socio Sanitaria Territoriale Grande Ospedale Metropolitano Niguarda (IT)
- Azienda Socio Sanitaria Territoriale di Cremona (IT)
- Thoracic Oncology, Medical Oncology Department, Fondazione IRCCS Istituto Nazionale dei Tumori, 20133 Milan, Italy
- Corresponding author
- Petrelli, Fausto
- ORCID
- Venue
- Cancers
- Publisher
- MDPI AG
- Published
- 2020-02-27
- Volume
- 12
- Issue
- 3
- Pages
- 546
- ISSN
- 2072-6694 (ISSN-L)
- PMC
- PMC7139305
- OpenAlex
- W3009486036
- Cited by
- 300
- References
- 44
- Citations by year
- 2026: 27 · 2025: 45 · 2024: 49 · 2023: 60 · 2022: 58 · 2021: 45 · 2020: 16
- FWCI
- 4.80
- Type
- journal article
- Language
- en
- Open access
- gold
- dx.doi.org
- Licence
- Locations
- Cancers (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Archivio Istituzionale della Ricerca (Universita Degli Studi Di Milano) (submittedVersion, other-oa)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- IrInSubria (University of Insubria) (submittedVersion)
- Topics
- Health Sciences › Medicine › Oncology › Cancer Immunotherapy and Biomarkers
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Adrenal Hormones and Disorders
- Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Toxicology › Pharmacovigilance and Adverse Drug Reactions
- Keywords
- immune checkpoint inhibitors, glucocorticoids, corticosteroid use, overall survival, progression-free survival, cancer immunotherapy toxicity, supportive care, brain metastases, adverse event management
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