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 Tahbaz9, Thomas Powles16, Axel Bex17. 1. Department of Urology, University Hospital Tuebingen, 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, Prague, 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, Charité - Universitätsmedizin Berlin, Berlin, Germany. 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, UK; Gravesham NHS Trust, Dartford, UK. 16. The Royal Free NHS Trust and Barts Cancer Institute, Queen Mary University of London, London, UK. 17. 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@nki.nl.
Abstract
Adjuvant treatment of nonmetastatic high-risk renal cell carcinoma is an unmet medical need. In the past, several tyrosine kinase inhibitor trials have failed to demonstrate an improvement of disease-free survival (DFS) in this setting. Only one trial (S-TRAC) provided evidence for improved DFS with sunitinib but without an overall survival (OS) signal. Keynote-564 is the first trial of an immune checkpoint inhibitor that significantly improved DFS with adjuvant pembrolizumab, a programmed death receptor-1 antibody, in clear cell renal cell carcinoma with a high risk of relapse. The intention-to-treat population, which included a group of patients after metastasectomy and no evidence of disease (M1 NED), had a significant DFS benefit. The OS data are not mature as yet. The Renal Cell Carcinoma Guideline Panel issues a weak recommendation for the adjuvant use of pembrolizumab for high-risk clear cell renal carcinoma, as defined by the trial until final OS data are available. However, the trial reilluminates the discussion on when and in whom metastasectomy should be performed. Here, caution is necessary not to perform metastasectomy in patients with poor prognostic features and rapid progressive disease, which must be excluded by a confirmatory scan of disease status prior to planned metastasectomy. PATIENT SUMMARY: New data from the adjuvant immune checkpoint inhibitor trial with pembrolizumab (a programmed death receptor-1 antibody) for the treatment of high-risk clear cell renal cell carcinoma (ccRCC) after surgery showed that the drug prolonged the period of being cancer free significantly, although whether it prolonged survival remained uncertain. Consequently, pembrolizumab is cautiously recommended as additional (ie, adjuvant) treatment in high-risk ccRCC after kidney cancer surgery.
Adjuvant treatment of nonmetastatic high-risk renal cell carcinoma is an unmet medical need. In the past, several tyrosine kinase inhibitor trials have failed to demonstrate an improvement of disease-free survival (DFS) in this setting. Only one trial (S-TRAC) provided evidence for improved DFS with sunitinib but without an overall survival (OS) signal. Keynote-564 is the first trial of an immune checkpoint inhibitor that significantly improved DFS with adjuvant pembrolizumab, a programmed death receptor-1 antibody, in clear cell renal cell carcinoma with a high risk of relapse. The intention-to-treat population, which included a group of patients after metastasectomy and no evidence of disease (M1 NED), had a significant DFS benefit. The OS data are not mature as yet. The Renal Cell Carcinoma Guideline Panel issues a weak recommendation for the adjuvant use of pembrolizumab for high-risk clear cell renal carcinoma, as defined by the trial until final OS data are available. However, the trial reilluminates the discussion on when and in whom metastasectomy should be performed. Here, caution is necessary not to perform metastasectomy in patients with poor prognostic features and rapid progressive disease, which must be excluded by a confirmatory scan of disease status prior to planned metastasectomy. PATIENT SUMMARY: New data from the adjuvant immune checkpoint inhibitor trial with pembrolizumab (a programmed death receptor-1 antibody) for the treatment of high-risk clear cell renal cell carcinoma (ccRCC) after surgery showed that the drug prolonged the period of being cancer free significantly, although whether it prolonged survival remained uncertain. Consequently, pembrolizumab is cautiously recommended as additional (ie, adjuvant) treatment in high-risk ccRCC after kidney cancer surgery.
Authors: Giuseppe Fallara; Alessandro Larcher; Giuseppe Rosiello; Daniele Raggi; Laura Marandino; Alberto Martini; Giuseppe Basile; Gianmarco Colandrea; Daniele Cignoli; Federico Belladelli; Chiara Re; Giacomo Musso; Francesco Cei; Roberto Bertini; Alberto Briganti; Andrea Salonia; Francesco Montorsi; Andrea Necchi; Umberto Capitanio Journal: World J Urol Date: 2022-09-20 Impact factor: 3.661