First-line treatment for advanced ccRCC...Lenvatinib–pembrolizumab [I, A; ESMO-MCBS v1.1 score: 4] is now FDA-approved but not EMA-approved and joins other PD-1 inhibitor–VEGFR-targeted combinations (axitinib–pembrolizumab [I, A; ESMO-MCBS v1.1 score: 4] or cabozantinib–nivolumab [I, A; ESMO-MCBS v1.1 score: 4]) to be recommended for first-line treatment of advanced ccRCC, irrespective of the International Metastatic RCC Database Consortium (IMDC) risk groups.

First-line therapy for clear cell histology: Preferred regimens…Cabozantinib + nivolumab

Overall, greater proportions of pts receiving N+C had deeper responses vs SUN (CR, PR1, PR2; Table). Deeper responses with N+C were associated with improved 12-mo PFS rate vs SUN for CR (94.9% vs 82.4%), PR1 (81.3% vs 37.5%), and PR2 (72.1% vs 53.2%). In both arms, increasingly deeper response led to better OS outcome; yet OS rates and medians were comparable between arms for CR, PR1, PR2, and PR3. In CheckMate 9ER, more pts receiving N+C achieved deeper responses vs SUN. Deeper responses were generally associated with improved PFS and OS.