Zhenjie Wu1, Qi Chen2, Le Qu3, Mingmin Li4, Linhui Wang5, Maria C Mir6, Umberto Carbonara7, Savio D Pandolfo8, Peter C Black9, Asit K Paul10, Giuseppe Di Lorenzo11, Francesco Porpiglia12, Andrea Mari13, Andrea Necchi14, Morgan Rouprêt15, Sarah P Psutka16, Riccardo Autorino8. 1. Department of Urology, Changhai Hospital, Naval Medical University, Shanghai, China. 2. Department of Health Statistics, Naval Medical University, Shanghai, China. 3. Department of Urology, Jinling Hospital, Clinical School of Medical College, Nanjing University, Nanjing, China. Electronic address: septsoul@hotmail.com. 4. Department of Radiology, Changhai Hospital, Naval Medical University, Shanghai, China. Electronic address: limingmin421@sina.com. 5. Department of Urology, Changhai Hospital, Naval Medical University, Shanghai, China. Electronic address: wanglinhui@smmu.edu.cn. 6. Department of Urology, Valencian Oncology Institute Foundation, FIVO, Valencia, Spain. 7. Department of Urology, Aldo Moro University, Bari, Italy. 8. Division of Urology, VCU Health System, Richmond, VA, USA. 9. Department of Urologic Sciences, The University of British Columbia, Vancouver, British Columbia, Canada. 10. Division of Hematology, Oncology and Palliative Care, Department of Internal Medicine, VCU Massey Cancer Center, Virginia Commonwealth University, Richmond, VA, USA. 11. Oncology Unit, Andrea Tortora Hospital, ASL Salerno, Pagani, Italy; Vincenzo Tiberio Department of Medicine and Health Sciences, University of Molise, Campobasso, Italy. 12. Department of Urology, San Luigi Gonzaga Hospital, University of Turin, Orbassano, Italy. 13. Department of Clinical and Experimental Medicine, University of Florence. Unit of Oncologic Minimally-Invasive Urology and Andrology, Careggi Hospital, Florence, Italy. 14. Genitourinary Medical Oncology, IRCCS San Raffaele Hospital and Scientific Institute, Milan, Italy. 15. Department of Urology, GRC n°5, Predictive Onco-Uro, AP-HP, Hôpital Pitié-Salpêtrière, Sorbonne University, Paris, France. 16. Department of Urology, University of Washington, Seattle Cancer Care Alliance, Seattle, WA, USA.
Abstract
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.
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.