Characteristics and clinical significance of cutaneous immune-related adverse events during atezolizumab therapy: An individual participant data meta-analysis

Background The spectrum of cutaneous immune-related adverse events (cirAEs) has been described, and the occurrence of cirAEs may be associated with improved survival. However, the accuracy of these findings is limited by inconsistent classification. Aim This study was designed to determine the type, incidence, and timing of cirAEs and their impacts on survival in cancer patients treated with atezolizumab by using the Medical Dictionary for Regulatory Activities (MedDRA) classification. Methods The Vivli platform was used to search for randomised controlled trials (RCTs) on atezolizumab. Patients with individual patient data (IPD) were enrolled in the study. Both 1-stage pooled analysis and 2-stage meta-analysis were used to estimate the survival outcomes of the occurrence of cirAEs during atezolizumab therapy, as well as their types, incidences, and timing. Results Fifteen RCTs having IPDs of 5870 patients were enrolled in this study. The incidence was 27.5% in this study, with rash/eruption/exanthem (83.9%) being the most frequent cirAEs. The earliest types to occur were alopecia. The occurrence of cirAE was an independent protective factor for both overall survival (OS, hazard ratio [HR]=0.40-0.72) and progression-free survival (PFS, HR=0.52-0.84). However, with respect to specific types, urticaria, erythema, alopecia, etc. were found to be independent protective factors for OS, whereas dry skin, purpura, dermatitis/eczema, etc. were found to be independent protective factors for PFS. Regarding the impact of management and outcomes, cirAE following medical treatment was an independent protective factor for both OS (HR=0.731, 0.622-0.859, P<0.001) and PFS (HR=0.785, 0.699-0.881, P<0.001). Limitations No patients treated with Programmed Death-1 (PD-1) or Cytotoxic T-Lymphocyte associated Antigen 4 (CTLA-4) agonists were enrolled. Conclusions Atezolizumab-induced cirAEs cover almost all types of dermatological diseases, with varied timing and severity. CirAEs, in general, are linked to improved treatment responses, but different types have different prognostic significance. The treatment of cirAE could influence cancer survival, suggesting the necessity of active management of cirAEs during atezolizumab therapy.