Adverse Events of Immune Checkpoint Inhibitors Therapy for Urologic Cancer Patients in Clinical Trials: A Collaborative Systematic Review and Meta-analysis

摘要

? 2022 The Author(s)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 22 942 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.