Peter C Black1, Nimira S Alimohamed2, David Berman3, Normand Blais4, Bernhard Eigl5, Pierre I Karakiewicz6, Wassim Kassouf7, Girish S Kulkarni8, Michael Ong9, Alan Spatz10, Srikala S Sridhar11, Tracy Stockley12, Theodorus van der Kwast13, Huong Hew14, Laura Park-Wyllie14, Scott A North15. 1. Department of Urologic Sciences, University of British, Columbia, Vancouver, BC, Canada. 2. Tom Baker Cancer Centre, Calgary, AB, Canada. 3. Queen's Cancer Research Institute, Kingston, ON, Canada. 4. Division of Medical Oncology/Hematology, Centre hospitalier de l'Université de Montréal, Montreal, QC, Canada. 5. [insert]. 6. Service d'urologie, Centre hospitalier de l'Université de Montréal, Montreal, QC, Canada. 7. Department of Urology, McGill University Health Centre, Montreal, QC, Canada. 8. Departments of Surgery (Urology), Princess Margaret Cancer Centre and the University Health Network, University of Toronto, Toronto, ON, Canada. 9. Division of Medical Oncology, University of Ottawa, Ottawa, ON, Canada. 10. Departments of Pathology and Oncology at McGill University, Montreal, QC, Canada. 11. Departments of Medical Oncology, Princess Margaret Cancer Centre and the University Health Network, University of Toronto, Toronto, ON, Canada. 12. Department of Clinical Laboratory Genetics, University Health Network, Toronto, ON, Canada. 13. Department of Pathology, University Health Network, Toronto, ON, Canada. 14. Medical Affairs, Janssen Inc, Toronto, ON, Canada. 15. Division of Medical Oncology, University of Alberta, Edmonton, AB, Canada.
Abstract
INTRODUCTION: Advanced urothelial carcinoma has been challenging to treat due to limited treatment options, poor response rates, and poor long-term survival. New treatment options hold the promise of improved outcomes for these patients. METHODS: A multidisciplinary working group drafted a management algorithm for advanced urothelial carcinoma using "consensus development conference" methodology. A targeted literature search identified new and emerging treatments for inclusion in the management algorithm. Published clinical data were considered during the algorithm development process, as well as the risks and benefits of the treatment options. Biomarkers to guide patient selection in clinical trials for new treatments were incorporated into the algorithm. RESULTS: The advanced urothelial carcinoma management algorithm includes newly approved first-line anti-programmed death receptor-1 (PD1)/programmed death-ligand 1 (PD-L1) therapies, a newly approved anti-fibroblast growth factor receptors (FGFR) therapy, and an emerging anti-Nectin 4 therapy, which have had encouraging results in phase 2 trials for second-line and third-line therapy, respectively. This algorithm also incorporates suggestions for biomarker testing of PD-L1 expression and FGFR gene alterations. CONCLUSIONS: Newly approved and emerging therapies are starting to cover an unmet need for more treatment options, better response rates, and improved overall survival in advanced urothelial carcinoma. The management algorithm provides guidance on how to incorporate these new options, and their associated biomarkers, into clinical practice.
INTRODUCTION: Advanced urothelial carcinoma has been challenging to treat due to limited treatment options, poor response rates, and poor long-term survival. New treatment options hold the promise of improved outcomes for these patients. METHODS: A multidisciplinary working group drafted a management algorithm for advanced urothelial carcinoma using "consensus development conference" methodology. A targeted literature search identified new and emerging treatments for inclusion in the management algorithm. Published clinical data were considered during the algorithm development process, as well as the risks and benefits of the treatment options. Biomarkers to guide patient selection in clinical trials for new treatments were incorporated into the algorithm. RESULTS: The advanced urothelial carcinoma management algorithm includes newly approved first-line anti-programmed death receptor-1 (PD1)/programmed death-ligand 1 (PD-L1) therapies, a newly approved anti-fibroblast growth factor receptors (FGFR) therapy, and an emerging anti-Nectin 4 therapy, which have had encouraging results in phase 2 trials for second-line and third-line therapy, respectively. This algorithm also incorporates suggestions for biomarker testing of PD-L1 expression and FGFR gene alterations. CONCLUSIONS: Newly approved and emerging therapies are starting to cover an unmet need for more treatment options, better response rates, and improved overall survival in advanced urothelial carcinoma. The management algorithm provides guidance on how to incorporate these new options, and their associated biomarkers, into clinical practice.
Authors: Thomas Powles; Jonathan E Rosenberg; Guru P Sonpavde; Yohann Loriot; Ignacio Durán; Jae-Lyun Lee; Nobuaki Matsubara; Christof Vulsteke; Daniel Castellano; Chunzhang Wu; Mary Campbell; Maria Matsangou; Daniel P Petrylak Journal: N Engl J Med Date: 2021-02-12 Impact factor: 91.245