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 journalArticle

1445 Citations (Scopus)

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 (US)
JournalThe Lancet
DOIs
StateAccepted/In press - 2016

Fingerprint

Platinum
Carcinoma
Drug Therapy
Ligands
Therapeutics
MPDL3280A
Neoplasms
Tumor Microenvironment
North America
Paraffin
Formaldehyde
Autoimmune Diseases
Immunoglobulins
Immunohistochemistry
Monoclonal Antibodies
Research Personnel
Infection
Pharmaceutical Preparations
Population

ASJC Scopus subject areas

  • Medicine(all)

Cite this

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

In: The Lancet, 2016.

Research output: Contribution to journalArticle

Rosenberg, JE, Hoffman-Censits, J, Powles, T, van der Heijden, MS, Balar, AV, Necchi, A, Dawson, N, O'Donnell, PH, Balmanoukian, A, Loriot, Y, Srinivas, S, Retz, MM, Grivas, P, Joseph, RW, Galsky, MD, Fleming, MT, Petrylak, DP, Perez-Gracia, JL, Burris, HA, Castellano, D, Canil, C, Bellmunt, J, Bajorin, D, Nickles, D, Bourgon, R, Frampton, GM, Cui, N, Mariathasan, S, Abidoye, O, Fine, GD & Dreicer, R 2016, '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', The Lancet. https://doi.org/10.1016/S0140-6736(16)00561-4
Rosenberg, Jonathan E. ; Hoffman-Censits, Jean ; Powles, Tom ; van der Heijden, Michiel S. ; Balar, Arjun V. ; Necchi, Andrea ; Dawson, Nancy ; O'Donnell, Peter H. ; Balmanoukian, Ani ; Loriot, Yohann ; Srinivas, Sandy ; Retz, Margitta M. ; Grivas, Petros ; Joseph, Richard W ; Galsky, Matthew D. ; Fleming, Mark T. ; Petrylak, Daniel P. ; Perez-Gracia, Jose Luis ; Burris, Howard A. ; Castellano, Daniel ; Canil, Christina ; Bellmunt, Joaquim ; Bajorin, Dean ; Nickles, Dorothee ; Bourgon, Richard ; Frampton, Garrett M. ; Cui, Na ; Mariathasan, Sanjeev ; Abidoye, Oyewale ; Fine, Gregg D. ; Dreicer, Robert. / 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. In: The Lancet. 2016.
@article{10958660a8754554b4d0930fa0107009,
title = "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",
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 (",
author = "Rosenberg, {Jonathan E.} and Jean Hoffman-Censits and Tom Powles and {van der Heijden}, {Michiel S.} and Balar, {Arjun V.} and Andrea Necchi and Nancy Dawson and O'Donnell, {Peter H.} and Ani Balmanoukian and Yohann Loriot and Sandy Srinivas and Retz, {Margitta M.} and Petros Grivas and Joseph, {Richard W} and Galsky, {Matthew D.} and Fleming, {Mark T.} and Petrylak, {Daniel P.} and Perez-Gracia, {Jose Luis} and Burris, {Howard A.} and Daniel Castellano and Christina Canil and Joaquim Bellmunt and Dean Bajorin and Dorothee Nickles and Richard Bourgon and Frampton, {Garrett M.} and Na Cui and Sanjeev Mariathasan and Oyewale Abidoye and Fine, {Gregg D.} and Robert Dreicer",
year = "2016",
doi = "10.1016/S0140-6736(16)00561-4",
language = "English (US)",
journal = "The Lancet",
issn = "0140-6736",
publisher = "Elsevier Limited",

}

TY - JOUR

T1 - Atezolizumab in patients with locally advanced and metastatic urothelial carcinoma who have progressed following treatment with platinum-based chemotherapy

T2 - A single-arm, multicentre, phase 2 trial

AU - Rosenberg, Jonathan E.

AU - Hoffman-Censits, Jean

AU - Powles, Tom

AU - van der Heijden, Michiel S.

AU - Balar, Arjun V.

AU - Necchi, Andrea

AU - Dawson, Nancy

AU - O'Donnell, Peter H.

AU - Balmanoukian, Ani

AU - Loriot, Yohann

AU - Srinivas, Sandy

AU - Retz, Margitta M.

AU - Grivas, Petros

AU - Joseph, Richard W

AU - Galsky, Matthew D.

AU - Fleming, Mark T.

AU - Petrylak, Daniel P.

AU - Perez-Gracia, Jose Luis

AU - Burris, Howard A.

AU - Castellano, Daniel

AU - Canil, Christina

AU - Bellmunt, Joaquim

AU - Bajorin, Dean

AU - Nickles, Dorothee

AU - Bourgon, Richard

AU - Frampton, Garrett M.

AU - Cui, Na

AU - Mariathasan, Sanjeev

AU - Abidoye, Oyewale

AU - Fine, Gregg D.

AU - Dreicer, Robert

PY - 2016

Y1 - 2016

N2 - 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 (

AB - 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 (

UR - http://www.scopus.com/inward/record.url?scp=84959577118&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84959577118&partnerID=8YFLogxK

U2 - 10.1016/S0140-6736(16)00561-4

DO - 10.1016/S0140-6736(16)00561-4

M3 - Article

C2 - 26952546

AN - SCOPUS:84959577118

JO - The Lancet

JF - The Lancet

SN - 0140-6736

ER -