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The treatment paradigm for treatment-naive metastatic clear cell renal cell carcinoma continued to evolve in 2019 as three phase III randomized controlled trials were reported comparing sunitinib with combination immune checkpoint inhibitors and VEGF-targeted therapy. Pembrolizumab plus axitinib and avelumab plus axitinib became new treatment options for untreated patients, irrespective of risk group or PD-L1 expression.