Luigi Nocera1,2, Pierre I Karakiewicz1, Mike Wenzel1,3, Zhe Tian1, Shahrokh F Shariat4,5,6,7,8,9, Fred Saad1, Felix K H Chun3, Alberto Briganti2, Anil Kapoor10, Aly-Khan Lalani10. 1. Cancer Prognostics and Health Outcomes Unit, Division of Urology, University of Montreal Health Center, Montreal, Quebec, Canada. 2. Division of Experimental Oncology/Unit of Urology, URI, Urological Research Institute, IRCCS San Raffaele Scientific Institute, Milan, Italy. 3. Department of Urology, University Hospital Frankfurt, Frankfurt am Main, Germany. 4. Department of Urology, Comprehensive Cancer Center, Medical University of Vienna, Vienna, Austria. 5. Departments of Urology, Weill Cornell Medical College, New York, New York. 6. Department of Urology, University of Texas Southwestern, Dallas, Texas. 7. Department of Urology, Second Faculty of Medicine, Charles University, Prague, Czech Republic. 8. Institute for Urology and Reproductive Health, I.M. Sechenov First Moscow State Medical University, Moscow, Russia. 9. Division of Urology, Department of Special Surgery, Jordan University Hospital, The University of Jordan, Amman, Jordan. 10. Juravinski Cancer Centre, McMaster University, Hamilton, Ontario, Canada.
Abstract
PURPOSE: Four recent first-line clinical trials leveraging immune-oncology agents demonstrated an overall survival (OS) benefit relative to sunitinib. We aimed to provide formal comparisons among immune-oncology combinations in terms of OS, progression-free survival (PFS), objective response rates and treatment-related adverse events (AEs). MATERIALS AND METHODS: PubMed® database was searched for studies indexed from January 1, 2016 through March 6, 2021. Only phase III randomized clinical trials with proven OS benefit relative to sunitinib were included: CheckMate 214 (nivolumab plus ipilimumab [N+I]), KEYNOTE-426 (pembrolizumab plus axitinib [P+A]), CheckMate 9ER (nivolumab plus cabozantinib [N+C]) and KEYNOTE-581 (lenvatinib plus permbrolizumab [L+P]). OS represented the primary outcome. PFS, objective response rate and AEs represented secondary outcomes. RESULTS: Overall, 3,320 patients were included. Regarding OS, N+C ranked first, followed by L+P, P+A and N+I. Regarding PFS and objective response rate, L+P ranked first, followed by N+C, P+A and N+I. Finally, N+I ranked first with respect to lowest grade 3+ AEs, followed by P+A, N+C and L+P. Differences in followup duration, risk grouping and nephrectomy rates distinguish the studies. CONCLUSIONS: N+C may provide the most favorable OS, L+P the most favorable PFS and ORRs, and N+I the lowest toxicity. Population differences may potentially undermine the generalizability and the robustness of findings of metastatic renal cell carcinoma.
PURPOSE: Four recent first-line clinical trials leveraging immune-oncology agents demonstrated an overall survival (OS) benefit relative to sunitinib. We aimed to provide formal comparisons among immune-oncology combinations in terms of OS, progression-free survival (PFS), objective response rates and treatment-related adverse events (AEs). MATERIALS AND METHODS: PubMed® database was searched for studies indexed from January 1, 2016 through March 6, 2021. Only phase III randomized clinical trials with proven OS benefit relative to sunitinib were included: CheckMate 214 (nivolumab plus ipilimumab [N+I]), KEYNOTE-426 (pembrolizumab plus axitinib [P+A]), CheckMate 9ER (nivolumab plus cabozantinib [N+C]) and KEYNOTE-581 (lenvatinib plus permbrolizumab [L+P]). OS represented the primary outcome. PFS, objective response rate and AEs represented secondary outcomes. RESULTS: Overall, 3,320 patients were included. Regarding OS, N+C ranked first, followed by L+P, P+A and N+I. Regarding PFS and objective response rate, L+P ranked first, followed by N+C, P+A and N+I. Finally, N+I ranked first with respect to lowest grade 3+ AEs, followed by P+A, N+C and L+P. Differences in followup duration, risk grouping and nephrectomy rates distinguish the studies. CONCLUSIONS: N+C may provide the most favorable OS, L+P the most favorable PFS and ORRs, and N+I the lowest toxicity. Population differences may potentially undermine the generalizability and the robustness of findings of metastatic renal cell carcinoma.
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Authors: Luigi Nocera; Giuseppe Fallara; Daniele Raggi; Federico Belladelli; Daniele Robesti; Francesco Montorsi; Pierre I Karakiewicz; Bernard Malavaud; Guillaume Ploussard; Andrea Necchi; Alberto Martini Journal: Front Oncol Date: 2022-09-05 Impact factor: 5.738