Atezolizumab in patients with locally advanced and metastatic urothelial carcinoma who have progressed following treatment with platinum-based chemotherapy: A single-arm, multicentre, phase 2 trial

Jonathan E. Rosenberg, Jean Hoffman-Censits, Tom Powles, Michiel S. Van Der Heijden, Arjun V. Balar, Andrea Necchi, Nancy Dawson, Peter H. O'Donnell, Ani Balmanoukian, Yohann Loriot, Sandy Srinivas, Margitta M. Retz, Petros Grivas, Richard W. Joseph, Matthew D. Galsky, Mark T. Fleming, Daniel P. Petrylak, Jose Luis Perez-Gracia, Howard A. Burris, Daniel CastellanoChristina Canil, Joaquim Bellmunt, Dean Bajorin, Dorothee Nickles, Richard Bourgon, Garrett M. Frampton, Na Cui, Sanjeev Mariathasan, Oyewale Abidoye, Gregg D. Fine, Robert Dreicer

Research output: Contribution to journalArticlepeer-review

Abstract

Background Patients with metastatic urothelial carcinoma have few treatment options after failure of platinum-based chemotherapy. In this trial, we assessed treatment with atezolizumab, an engineered humanised immunoglobulin G1 monoclonal antibody that binds selectively to programmed death ligand 1 (PD-L1), in this patient population. Methods For this multicentre, single-arm, two-cohort, phase 2 trial, patients (aged ≥18 years) with inoperable locally advanced or metastatic urothelial carcinoma whose disease had progressed after previous platinum-based chemotherapy were enrolled from 70 major academic medical centres and community oncology practices in Europe and North America. Key inclusion criteria for enrolment were Eastern Cooperative Oncology Group performance status of 0 or 1, measurable disease defined by Response Evaluation Criteria In Solid Tumors version 1.1 (RECIST v1.1), adequate haematological and end-organ function, and no autoimmune disease or active infections. Formalin-fixed paraffin-embedded tumour specimens with sufficient viable tumour content were needed from all patients before enrolment. Patients received treatment with intravenous atezolizumab (1200 mg, given every 3 weeks). PD-L1 expression on tumour-infiltrating immune cells (ICs) was assessed prospectively by immunohistochemistry. The co-primary endpoints were the independent review facility-assessed objective response rate according to RECIST v1.1 and the investigator-assessed objective response rate according to immune-modified RECIST, analysed by intention to treat. A hierarchical testing procedure was used to assess whether the objective response rate was significantly higher than the historical control rate of 10% at an α level of 0·05. This study is registered with ClinicalTrials.gov, number NCT02108652. Findings Between May 13, 2014, and Nov 19, 2014, 486 patients were screened and 315 patients were enrolled into the study. Of these patients, 310 received atezolizumab treatment (five enrolled patients later did not meet eligibility criteria and were not dosed with study drug). The PD-L1 expression status on infiltrating immune cells (ICs) in the tumour microenvironment was defined by the percentage of PD-L1-positive immune cells: IC0 (

Original languageEnglish
Pages (from-to)1909-1920
Number of pages12
JournalLancet
Volume387
Issue number10031
DOIs
Publication statusPublished - May 7 2016

ASJC Scopus subject areas

  • Medicine(all)

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