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…Axitinib + Pembrolizumab

The secondary endpoints included objective response rate (ORR) and duration of response (DOR). The median study follow-up was 43 (range, 36–51) mo. Benefit with pembrolizumab plus axitinib versus sunitinib was maintained for OS (hazard ratio [HR], 0.73 [95% confidence interval {CI}, 0.60–0.88]), PFS (HR, 0.68 [95% CI, 0.58–0.80]), and ORR (60% vs 40%)....Extended results of KEYNOTE-426 support pembrolizumab plus axitinib as the standard of care for advanced clear cell renal cell carcinoma.

For pembro + axi vs sunitinib, ORR was 60.4% vs 39.6% (P<0.0001); CR rate was 10.0% vs 3.5%; median DOR was 23.6 mo (range 1.4+ to 43.4+) vs 15.3 mo (range, 2.3-42.8+)….pembro + axi continues to demonstrate superior efficacy over sunitinib with respect to OS, PFS, and ORR...