Jens Bedke1, Laurence Albiges2, Umberto Capitanio3, Rachel H Giles4, Milan Hora5, Thomas B Lam6, Börje Ljungberg7, Lorenzo Marconi8, Tobias Klatte9, Alessandro Volpe10, Yasmin Abu-Ghanem11, Saeed Dabestani12, Sergio Fernández Pello13, Fabian Hofmann14, Teele Kuusk15, Rana Tahbaz16, Thomas Powles17, Axel Bex18. 1. Department of Urology, University Hospital Tübingen, Tuebingen, Germany; German Cancer Consortium (DKTK) and German Cancer Research Center (DKFZ), Heidelberg, Germany. 2. Department of Cancer Medicine, Gustave Roussy, Université Paris-Saclay, Villejuif, France. 3. Department of Urology, San Raffaele Scientific Institute, Milan, Italy; Division of Experimental Oncology/Unit of Urology, URI, IRCCS San Raffaele Hospital, Milan, Italy. 4. International Kidney Cancer Coalition (IKCC), Duivendrecht, The Netherlands. 5. Department of Urology, University Hospital Pilsen and Faculty of Medicine in Pilsen, Charles University, Czech Republic. 6. Academic Urology Unit, University of Aberdeen, Aberdeen, UK; Department of Urology, Aberdeen Royal Infirmary, Aberdeen, UK. 7. Department of Surgical and Perioperative Sciences, Urology and Andrology, Umeå University, Umeå, Sweden. 8. Department of Urology, Coimbra University Hospital, Coimbra, Portugal. 9. Department of Urology, Royal Bournemouth Hospital, Bournemouth, UK; Department of Surgery, University of Cambridge, Cambridge, UK. 10. Department of Urology, University of Eastern Piedmont, Maggiore della Carità Hospital, Novara, Italy. 11. Department of Urology, Chaim Sheba Medical Center, Tel-Hashomer, Ramat-Gan, Israel. 12. Department of Translational Medicine, Division of Urological Cancers, Lund University, Malmö, Sweden. 13. Department of Urology, Cabueñes University Hospital, Gijón, Spain. 14. Department of Urology, Sunderby Sjukhus, Umeå University, Luleå, Sweden. 15. Department of Urology, Darent Valley Hospital, Dartford and Gravesham NHS Trust, Dartford, UK. 16. Department of Urology, Charité University Hospital Berlin, Germany. 17. The Royal Free NHS Trust and Barts Cancer Institute, Queen Mary University of London, London, UK. 18. The Royal Free London NHS Foundation Trust, London, UK; UCL Division of Surgery and Interventional Science, London, UK; Department of Urology, The Netherlands Cancer Institute, Antoni van Leeuwenhoek Hospital, Amsterdam, The Netherlands. Electronic address: a.bex@ucl.ac.uk.
Abstract
The recent randomized controlled phase III CLEAR trial results are the last to complement immune checkpoint inhibitor (ICI)-based doublet combination therapies for treatment-naïve metastatic clear-cell renal cell carcinoma. The CLEAR trial demonstrated an improved progression-free survival (PFS), overall survival (OS), and an objective response rate (ORR) benefit for the combination of lenvatinib plus pembrolizumab over sunitinib. The CheckMate-9ER trial update demonstrated an ongoing PFS, OS, and quality-of-life benefit for cabozantinib plus nivolumab over sunitinib as did the update of Keynote-426 for axitinib plus pembrolizumab in the intention-to-treat population, with a PFS benefit seen across all International Metastatic Database Consortium (IMDC) subgroups. In the IMDC intermediate- and poor-risk groups, the CheckMate-214 trial of ipilimumab plus nivolumab confirmed the OS benefit with a PFS plateauing after 30 months. The RCC Guidelines Panel recommends three tyrosine kinase inhibitors + ICI combinations of axitinib plus pembrolizumab, cabozantinib plus nivolumab, and lenvatinib plus pembrolizumab across all IMDC risk groups in advanced first-line RCC, and dual immunotherapy of ipilimumab and nivolumab in IMDC intermediate- and poor-risk groups. PATIENT SUMMARY: New data from combination trials with immune checkpoint inhibitors for advanced kidney cancer confirm a survival benefit for lenvatinib plus pembrolizumab, cabozantinib plus nivolumab (with improved quality-of-life), axitinib plus pembrolizumab, and ipilimumab plus nivolumab. These combination therapies are recommended as first-line treatment for advanced kidney cancer.
The recent randomized controlled phase III CLEAR trial results are the last to complement immune checkpoint inhibitor (ICI)-based doublet combination therapies for treatment-naïve metastatic clear-cell renal cell carcinoma. The CLEAR trial demonstrated an improved progression-free survival (PFS), overall survival (OS), and an objective response rate (ORR) benefit for the combination of lenvatinib plus pembrolizumab over sunitinib. The CheckMate-9ER trial update demonstrated an ongoing PFS, OS, and quality-of-life benefit for cabozantinib plus nivolumab over sunitinib as did the update of Keynote-426 for axitinib plus pembrolizumab in the intention-to-treat population, with a PFS benefit seen across all International Metastatic Database Consortium (IMDC) subgroups. In the IMDC intermediate- and poor-risk groups, the CheckMate-214 trial of ipilimumab plus nivolumab confirmed the OS benefit with a PFS plateauing after 30 months. The RCC Guidelines Panel recommends three tyrosine kinase inhibitors + ICI combinations of axitinib plus pembrolizumab, cabozantinib plus nivolumab, and lenvatinib plus pembrolizumab across all IMDC risk groups in advanced first-line RCC, and dual immunotherapy of ipilimumab and nivolumab in IMDC intermediate- and poor-risk groups. PATIENT SUMMARY: New data from combination trials with immune checkpoint inhibitors for advanced kidney cancer confirm a survival benefit for lenvatinib plus pembrolizumab, cabozantinib plus nivolumab (with improved quality-of-life), axitinib plus pembrolizumab, and ipilimumab plus nivolumab. These combination therapies are recommended as first-line treatment for advanced kidney cancer.
Authors: Dennis Gürgen; Michael Becker; Mathias Dahlmann; Susanne Flechsig; Elke Schaeffeler; Florian A Büttner; Christian Schmees; Regina Bohnert; Jens Bedke; Matthias Schwab; Johann J Wendler; Martin Schostak; Burkhard Jandrig; Wolfgang Walther; Jens Hoffmann Journal: Front Oncol Date: 2022-06-21 Impact factor: 5.738