RT Journal Article T1 Update on the treatment of metastatic renal cell carcinoma. A1 Medina López, Rafael Antonio A1 Rivero Belenchon, Ines A1 Mazuecos-Quirós, Javier A1 Congregado-Ruíz, Carmen Belén A1 Couñago, Felipe K1 Antiangiogenic K1 Biomarkers K1 Immune checkpoint inhibitors K1 Metastatic renal cell carcinoma K1 Systemic treatment K1 Update AB Metastatic renal cell cancer (mRCC) management has undergone a paradigm shift in recent decades. The first revolution came with the emergence of vascular endothelial growth factor inhibitors; there was a second wave with the unprecedented success of checkpoint inhibitors, and then the latest approach, which is becoming the new care standard in mRCC, of combining these two strategies in different ways. Updated results of Checkmate-214 after 42 mo of follow-up were consistent with previously published results showing the superiority of nivolumab/ipilimumab over sunitinib in progression free survival (PFS), overall survival (OS), and objective response rate (ORR) in intermediate and high-risk patients. However, several studies presented at the American Society of Clinical Oncology 2020 suggested that the best place, and so far, the only one for nivolumab/ipilimumab is the frontline setting. The update on Keynote-426 after 23 mo of follow-up showed no superiority of pembroli-zumab/axitinib over sunitinib in favorable-risk mRCC, suggesting that it should no longer be the first line of choice in low-risk patients. Finally, the phase III Checkmate 9ER trial results revealed the superiority of nivolumab/cabozantinib vs sunitinib in PFS, OS, and ORR, providing a new first-line option among all International Metastatic RCC Database Consortium risk patients. Some phase II clinical trials also presented this year showed promising results with new combination therapies such as nivolumab/sitravatinib, cabozantinib/atezolizumab, and lenvatinib/pembrolizumab, providing promising grounds upon which to start phase III studies. In addition, other works are using novel therapeutic agents with different mechanisms of action, including telaglenastat (a glutaminase inhibitor), entinostat [an inhibitor of histone deacetylases (HDACs)], and olaparib and talazoparib, poly(ADP-ribose) polymerase inhibitors widely used in other tumors. However, some questions regarding mRCC management still need to be addressed, such as head-to-head comparisons between the current options, treatment sequencing, non-clear cell mRCC, and the role of biomarkers to ascertain the best treatment choice. SN 2218-4333 YR 2022 FD 2022 LK http://hdl.handle.net/10668/21655 UL http://hdl.handle.net/10668/21655 LA en DS RISalud RD Apr 9, 2025