Correlation Between Immune-related Adverse Event (IRAE) Occurrence and Clinical Outcome in Patients With Metastatic Renal Cell Carcinoma (mRCC) Treated With Nivolumab: IRAENE Trial, an Italian Multi-institutional Retrospective Study

Immunotherapy has brought clinical benefits to patients with metastatic renal cell cancer (mRCC). Most patients tolerate immunotherapy but serious immune-related adverse events (irAEs) have been reported. Some studies indicate a correlation between irAEs and clinical response in other cancer types (eg, lung cancer and melanoma). For patients with mRCC, the impact of irAE on clinical outcome is unknown. A retrospective review of 167 patients with mRCC treated with nivolumab as standard of care between March 2017 and January 2018 in 16 Italian centers was performed. irAEs were assessed using Common Terminology Criteria for Adverse Events (CTCAE) v.4.0. Any grade and grade 3/4 irAEs occurred in 46% and 8.9% of patients, respectively. The median time to appearance of irAEs was 10 weeks; 38.8% of patients required steroid treatment. The most common irAEs were cutaneous (33.7%) and gastrointestinal (23.3%). The median overall survival and progression-free survival were 20.13 and 7.86 months, respectively. Patients with irAEs showed a greater overall survival (hazard ratio, 0.38; 95% confidence interval [CI], 0.23-0.63) and progression-free survival (hazard ratio, 0.44; 95% CI, 0.29-0.66) benefit as well as better overall response rate (27.3% vs. 13.7%; odds ratio, 2.36; 95% CI, 1.03-5.44) and disease control rate (68.8% vs. 48%; odds ratio, 2.4; 95% CI, 1.23-4.67) if compared with those without irAEs. No correlation was found between steroid use and clinical outcomes. Our analysis revealed that the appearance of irAEs was associated with better outcomes in patients treated with nivolumab. This data may be limited by sample size and the retrospective nature of the study. In the past years, immunotherapy has demonstrated an important role in the treatment of several types of cancer. Some studies indicate a correlation between immune-related adverse events (irAEs) and clinical response in other cancer types. For patients with metastatic renal cell carcinoma, the impact of irAEs on clinical outcome is unknown. We conducted a retrospective observational review of 167 patients with metastatic renal cell carcinoma, previously treated with standard treatment, who received nivolumab in monotherapy as clinical practice. Any grade and grade 3/4 irAEs occurred in 46% and 8.9% of patients, respectively. Patients with irAEs showed a more significant overall survival and progression-free survival benefit, and better objective response rate and disease control rate if compared