PMID- 35101302 OWN - NLM STAT- MEDLINE DCOM- 20220418 LR - 20220430 IS - 1873-7560 (Electronic) IS - 0302-2838 (Linking) VI - 81 IP - 4 DP - 2022 Apr TI - Adverse Events of Immune Checkpoint Inhibitors Therapy for Urologic Cancer Patients in Clinical Trials: A Collaborative Systematic Review and Meta-analysis. PG - 414-425 LID - S0302-2838(22)00065-3 [pii] LID - 10.1016/j.eururo.2022.01.028 [doi] AB - CONTEXT: Therapies based on immune checkpoint inhibitors (ICIs) are transforming the treatment landscape of urologic oncology. Nevertheless, an exhaustive overview of the toxicity spectrum of these novel therapies has yet to be provided. OBJECTIVE: To comprehensively investigate the incidence and profile of ICI therapy-related adverse events (AEs) across urologic cancers. EVIDENCE ACQUISITION: We searched for all clinical trials investigating the role of ICI therapy published between January 2010 and September 2021. Studies involving urologic cancers with reported overall incidence or tabulated data of treatment-related AEs (trAEs) or immune-related AEs (irAEs) were included. A systematic review and meta-analysis was performed after protocol registration in PROSPERO (CRD42021276435). EVIDENCE SYNTHESIS: We identified 2638 records, of which 92 studies (including 22942 participants) met the inclusion criteria. The pooled overall incidence was 81.6% (95% confidence interval [CI] 78.0-84.7) for any-grade trAEs and 29.3% (95% CI 24.9-34.1) for grade >/=3 trAEs. The pooled overall incidence was 34.3% (95% CI 28.5-40.7) for any-grade irAEs and 10.2% (95%CI 8.2-12.7) for grade >/=3 irAEs. On a multivariable analysis, cancer type, therapy combination, clinical settings (perioperative vs advanced/metastatic), and drug exposure were independently associated with the occurrence of trAEs or irAEs. The overall rate of treatment-related mortality was 0.94% (140 of 14 899 participants), with pneumonitis (9.3%), pneumonia (7.9%), and respiratory failure (7.1%) being the most common causes. Immune-related mortality occurred in 0.26% (28 of 10 723) patients, with pneumonitis (35.7%), hepatic failure (10.7%), and hepatitis (7.1%) being most common. CONCLUSIONS: Our study provides a comprehensive overview of ICI-associated AEs in urologic cancer patients. The spectrum and incidence of AEs vary across cancer types, ICI types, clinical settings, and therapy combinations. These findings provide important guidance to clinicians in counseling and management of patients with urologic cancers. PATIENT SUMMARY: A high proportion of patients experience immune checkpoint inhibitor-associated toxicity. Physician and patient education is critical for early recognition and proper management. CI - Copyright (c) 2022 The Author(s). Published by Elsevier B.V. All rights reserved. FAU - Wu, Zhenjie AU - Wu Z AD - Department of Urology, Changhai Hospital, Naval Medical University, Shanghai, China. FAU - Chen, Qi AU - Chen Q AD - Department of Health Statistics, Naval Medical University, Shanghai, China. FAU - Qu, Le AU - Qu L AD - Department of Urology, Jinling Hospital, Clinical School of Medical College, Nanjing University, Nanjing, China. Electronic address: septsoul@hotmail.com. FAU - Li, Mingmin AU - Li M AD - Department of Radiology, Changhai Hospital, Naval Medical University, Shanghai, China. Electronic address: limingmin421@sina.com. FAU - Wang, Linhui AU - Wang L AD - Department of Urology, Changhai Hospital, Naval Medical University, Shanghai, China. Electronic address: wanglinhui@smmu.edu.cn. FAU - Mir, Maria C AU - Mir MC AD - Department of Urology, Valencian Oncology Institute Foundation, FIVO, Valencia, Spain. FAU - Carbonara, Umberto AU - Carbonara U AD - Department of Urology, Aldo Moro University, Bari, Italy. FAU - Pandolfo, Savio D AU - Pandolfo SD AD - Division of Urology, VCU Health System, Richmond, VA, USA. FAU - Black, Peter C AU - Black PC AD - Department of Urologic Sciences, The University of British Columbia, Vancouver, British Columbia, Canada. FAU - Paul, Asit K AU - Paul AK AD - Division of Hematology, Oncology and Palliative Care, Department of Internal Medicine, VCU Massey Cancer Center, Virginia Commonwealth University, Richmond, VA, USA. FAU - Di Lorenzo, Giuseppe AU - Di Lorenzo G AD - Oncology Unit, Andrea Tortora Hospital, ASL Salerno, Pagani, Italy; Vincenzo Tiberio Department of Medicine and Health Sciences, University of Molise, Campobasso, Italy. FAU - Porpiglia, Francesco AU - Porpiglia F AD - Department of Urology, San Luigi Gonzaga Hospital, University of Turin, Orbassano, Italy. FAU - Mari, Andrea AU - Mari A AD - Department of Clinical and Experimental Medicine, University of Florence. Unit of Oncologic Minimally-Invasive Urology and Andrology, Careggi Hospital, Florence, Italy. FAU - Necchi, Andrea AU - Necchi A AD - Genitourinary Medical Oncology, IRCCS San Raffaele Hospital and Scientific Institute, Milan, Italy. FAU - Roupret, Morgan AU - Roupret M AD - Department of Urology, GRC n degrees 5, Predictive Onco-Uro, AP-HP, Hopital Pitie-Salpetriere, Sorbonne University, Paris, France. FAU - Psutka, Sarah P AU - Psutka SP AD - Department of Urology, University of Washington, Seattle Cancer Care Alliance, Seattle, WA, USA. FAU - Autorino, Riccardo AU - Autorino R AD - Division of Urology, VCU Health System, Richmond, VA, USA. LA - eng PT - Journal Article PT - Meta-Analysis PT - Research Support, Non-U.S. Gov't PT - Review PT - Systematic Review DEP - 20220131 PL - Switzerland TA - Eur Urol JT - European urology JID - 7512719 RN - 0 (Immune Checkpoint Inhibitors) SB - IM MH - Female MH - Humans MH - *Immune Checkpoint Inhibitors/adverse effects MH - Incidence MH - Male MH - Radioimmunotherapy MH - *Urologic Neoplasms/drug therapy OTO - NOTNLM OT - *Adverse events OT - *Bladder OT - *Immune checkpoint inhibitors OT - *Immunotherapy OT - *Prostate cancer OT - *Renal cell carcinoma OT - *Renal pelvis OT - *Trials OT - *Ureter OT - *Urology OT - *Urothelial carcinoma EDAT- 2022/02/02 06:00 MHDA- 2022/04/19 06:00 CRDT- 2022/02/01 05:47 PHST- 2021/11/10 00:00 [received] PHST- 2021/12/23 00:00 [revised] PHST- 2022/01/13 00:00 [accepted] PHST- 2022/02/02 06:00 [pubmed] PHST- 2022/04/19 06:00 [medline] PHST- 2022/02/01 05:47 [entrez] AID - S0302-2838(22)00065-3 [pii] AID - 10.1016/j.eururo.2022.01.028 [doi] PST - ppublish SO - Eur Urol. 2022 Apr;81(4):414-425. doi: 10.1016/j.eururo.2022.01.028. Epub 2022 Jan 31.