(UroToday.com) There have been transformational changes in first-line therapy for patients with metastatic renal cell carcinoma (RCC) in the past three years. Foremost among these is the move from monotherapy to combination approaches. While CheckMate 214 first brought combination therapy with dual checkpoint inhibition (nivolumab and ipilimumab) to the forefront, subsequent studies have examined combinations of immune checkpoint inhibitors and tyrosine-kinase inhibitors in the first-line setting. One such combination is lenvatinib and pembrolizumab which, in the CLEAR trial (NCT02811861), was found to significantly improve progression-free survival (PFS), overall survival (OS), and objective response rate (ORR) as first-line therapy for patients with advanced RCC. In the Kidney and Bladder Poster session at the 2021 American Society of Clinical Oncology (ASCO) Annual Meeting, Dr. Viktor Grunwald presented a secondary analysis of the CLEAR trial examining treatment effect in various subgroups.