ctDNA guiding adjuvant immunotherapy in urothelial carcinoma

Thomas Powles (), Zoe June Assaf, Nicole Davarpanah, Romain Banchereau, Bernadett E. Szabados, Kobe C. Yuen, Petros Grivas, Maha Hussain, Stephane Oudard, Jürgen E. Gschwend, Peter Albers, Daniel Castellano, Hiroyuki Nishiyama, Siamak Daneshmand, Shruti Sharma, Bernhard G. Zimmermann, Himanshu Sethi, Alexey Aleshin, Maurizio Perdicchio, Jingbin Zhang, David S. Shames, Viraj Degaonkar, Xiaodong Shen, Corey Carter, Carlos Bais, Joaquim Bellmunt and Sanjeev Mariathasan ()
Additional contact information
Thomas Powles: Queen Mary University of London ECMC, Barts Health
Zoe June Assaf: Roche/Genentech
Nicole Davarpanah: Roche/Genentech
Romain Banchereau: Roche/Genentech
Bernadett E. Szabados: Queen Mary University of London
Kobe C. Yuen: Roche/Genentech
Petros Grivas: University of Washington
Maha Hussain: Northwestern University
Stephane Oudard: University of Paris
Jürgen E. Gschwend: Technical University Munich
Peter Albers: University Hospital Düsseldorf
Daniel Castellano: University Hospital 12 de Octubre, Medical Oncology Department CIBER-ONC
Hiroyuki Nishiyama: Faculty of Medicine University of Tsukuba
Siamak Daneshmand: USC Norris Comprehensive Cancer Center
Shruti Sharma: Natera, Inc
Bernhard G. Zimmermann: Natera, Inc
Himanshu Sethi: Natera, Inc
Alexey Aleshin: Natera, Inc
Maurizio Perdicchio: F. Hoffmann-La Roche Ltd
Jingbin Zhang: Hoffmann-La Roche Ltd, Mississauga
David S. Shames: Roche/Genentech
Viraj Degaonkar: Roche/Genentech
Xiaodong Shen: Roche/Genentech
Corey Carter: Roche/Genentech
Carlos Bais: Roche/Genentech
Joaquim Bellmunt: Harvard Medical School
Sanjeev Mariathasan: Roche/Genentech

Nature, 2021, vol. 595, issue 7867, 432-437

Abstract: Abstract Minimally invasive approaches to detect residual disease after surgery are needed to identify patients with cancer who are at risk for metastatic relapse. Circulating tumour DNA (ctDNA) holds promise as a biomarker for molecular residual disease and relapse1. We evaluated outcomes in 581 patients who had undergone surgery and were evaluable for ctDNA from a randomized phase III trial of adjuvant atezolizumab versus observation in operable urothelial cancer. This trial did not reach its efficacy end point in the intention-to-treat population. Here we show that ctDNA testing at the start of therapy (cycle 1 day 1) identified 214 (37%) patients who were positive for ctDNA and who had poor prognosis (observation arm hazard ratio = 6.3 (95% confidence interval: 4.45–8.92); P

Date: 2021
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DOI: 10.1038/s41586-021-03642-9

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