Combinations of immunotherapy drugs nivolumab plus ipilimumab and immunotherapy/vascular endothelial growth factor (VEGF) inhibitors are widely used for the treatment of metastatic renal cell carcinoma (RCC). However, limited information is available to compare the outcomes from different combinations.

At the virtual American Society of Clinical Oncology Genitourinary Cancers Symposium (ASCO GU) over the weekend, data from the International Metastatic RCC Database Consortium (IMDC) database was used to determine outcomes from treatment of metastatic RCC with immunotherapy combinations in the first line. The outcomes from three immunotherapy combinations (pembrolizumab plus axitinib, avelumab plus axitinib, and nivolumab plus cabozantinib) were compared with nivolumab plus ipilimumab.

There were 723 patients in the study, of which 571 patients were treated with nivolumab plus ipilimumab and 152 patients were treated with immunotherapy/VEGF inhibitor combinations. In patients with intermediate/poor risk RCC, cancer shrinkage (response rate) (37% versus 59%) and duration of treatment (4.6 versus 15.0 months) were lower and shorter for patients in the nivolumab plus ipilimumab group versus patients treated with immunotherapy/VEGF inhibitor combinations. However, there was no difference in time to next treatment and overall survival time.

Dose delays and steroids for the treatment of immune-related adverse events resulted in a longer time to next treatment and overall survival time compared to those patients without dose delays or steroid use, despite similar treatment durations.

In summary, while there were longer treatment durations and higher response rates with immunotherapy/VEGF inhibitor combinations, there were no differences in overall survival time and time to next treatment compared to nivolumab plus ipilimumab in patients with intermediate/poor-risk RCC. Serious immune-related adverse events were associated with longer overall survival time and time to next treatment. Both nivolumab plus ipilimumab and immunotherapy/VEGF inhibitor combinations are reasonable first-line treatments for metastatic RCC.

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