TY - JOUR
T1 - Partial Response and Stable Disease Correlate with Positive Outcomes in Atezolizumab-treated Patients with Advanced Urinary Tract Carcinoma
AU - Bedke, Jens
AU - Merseburger, Axel S.
AU - Loriot, Yohann
AU - Castellano, Daniel
AU - Choy, Ernest
AU - Duran, Ignacio
AU - Rosenberg, Jonathan E.
AU - Petrylak, Daniel P.
AU - Dreicer, Robert
AU - Perez-Gracia, Jose L.
AU - Hoffman-Censits, Jean H.
AU - Van Der Heijden, Michiel S.
AU - Pavlova, Julie
AU - Thiebach, Lars
AU - de Ducla, Sabine
AU - Fear, Simon
AU - Powles, Thomas
AU - Sternberg, Cora N.
N1 - Funding Information:
Financial disclosures: Jens Bedke certifies that all conflicts of interest, including specific financial interests and relationships and affiliations relevant to the subject matter or materials discussed in the manuscript (ie, employment/affiliation, grants or funding, consultancies, honoraria, stock ownership or options, expert testimony, royalties, or patents filed, received, or pending) are the following: Jens Bedke reports a consulting/advisory role for Astellas Pharma, Bristol-Myers Squibb, Eisai, Ipsen, MSD, Novartis, Roche, and AstraZeneca; a role in the speakers’ bureau of Pfizer, EUSA Pharma, Novartis, Roche, MSD, Ipsen, Eisai, and Bristol-Myers Squibb; and research funding from Bayer, Bristol-Myers Squibb, Exelixis, MSD, Pfizer, Roche, Novartis, Eisai, and Ipsen—all to the institution. Axel S. Merseburger reports a consultancy/advisory role for MSD, Bristol-Myers Squibb, Janssen-Cilag, Astellas Pharma, and Ipsen; a role in the speakers’ bureau of Ipsen; travel/accommodation/expenses from Janssen-Cilag, Astellas Pharma, and Ipsen; honoraria from Janssen-Cilag, Astellas Pharma, Ipsen, Roche, Bristol-Myers Squibb, Eisai, Takeda, Pfizer, and Novartis; and research funding from Novartis, AstraZeneca, Janssen-Cilag, Bristol-Myers Squibb, and Clovis—all to the institution. Yohann Loriot reports a grant and nonfinancial support from Roche for the SAUL study and funding of editorial support; a grant from Celsius; grants and personal fees from Sanofi, Janssen, and MSD; and personal fees from Astellas, AstraZeneca, Roche, BMS, Seattle Genetics, and Pfizer. Daniel Castellano reports research funding to the institution from Janssen Oncology; a role as an adviser/consultant in Janssen Oncology, Roche/Genentech, Astellas Pharma, AstraZeneca, Pfizer, Novartis, Ipsen, Bristol-Myers Squibb, MSD Oncology, Bayer, Lilly, Sanofi, Pierre Fabre, and Boehringer Ingelheim; travel/accommodation/expenses from Pfizer, Roche, Bristol-Myers Squibb, and AstraZeneca Spain. Ernest Choy reports personal fees from Chugai Pharma, Eli Lilly, Janssen, Novartis, Pfizer, Regeneron, Roche, Sanofi, UCB, Gilead, AbbVie, R-Pharm, SynAct Pharma, and ObsEva; and research grants from Chugai Pharma, Novartis, Pfizer, Roche, Sanofi, UCB, Biogen, and Bio-Cancer. Ignacio Duran reports a consulting/advisory role for Roche/Genentech, MSD Oncology, Bayer, Bristol-Myers Squibb, Seattle Genetics, Pharmacyclics, Janssen Oncology, and Novartis; travel/accommodation/expenses from Roche/Genentech and AstraZeneca Spain; honoraria from Bristol-Myers Squibb, Ipsen, Roche/Genentech, Janssen Oncology, MSD Oncology, and Astellas Pharma; and research funding from Roche/Genentech, AstraZeneca Spain, Janssen Oncology, and Astellas Pharma—all to the institution. Jonathan E. Rosenberg reports a consulting/advisory role for Lilly, Merck, Agensys, Roche/Genentech, AstraZeneca/MedImmune, Bristol-Myers Squibb, EMD Serono, Seattle Genetics, Bayer, Inovio Pharmaceuticals, BioClin Therapeutics, QED Therapeutics, Adicet Bio, Sensei Biotherapeutics, Fortress Biotech, Pharmacyclics, Western Oncolytics, GlaxoSmithKline, Janssen Oncology, and Astellas Pharma; travel/accommodation/expenses from Genentech/Roche and Bristol-Myers Squibb; patents/royalties: predictor of platinum sensitivity; stock/ownership at Illumina; honoraria from Bristol-Myers Squibb, AstraZeneca, Medscape, Vindico, Peerview, Chugai Pharma, Research to Practice, Intellisphere, Clinical Care Options, and ClinicalMind; and research funding from Mirati Therapeutics, Novartis, Viralytics, Genentech/Roche, Incyte, Seattle Genetics, Bayer, AstraZeneca, QED Therapeutics, Astellas Pharma, and Jounce Therapeutics—all to the institution. Daniel P. Petrylak reports a consulting/advisory role for Bayer, Exelixis, Pfizer, Roche, Astellas Pharma, AstraZeneca, Lilly, Amgen, Boehringer Ingelheim, Bristol-Myers Squibb, Clovis Oncology, Incyte, Janssen, Pharmacyclics, Seattle Genetics, Urogen Pharma, and Advanced Accelerator Applications; providing expert testimony for Celgene and Sanofi; stock/ownership interests in Bellicum Pharmaceuticals and Tyme; and research funding from Progenics, Sanofi, Endocyte, Genentech, Merck, Astellas Medivation, Novartis, AstraZeneca, Bayer, Lilly, Innocrin Pharma, MedImmune, Pfizer, Roche, Seattle Genetics, Clovis Oncology, Bristol-Myers Squibb, and Advanced Accelerator Applications—all to the institution. Robert Dreicer reports a consulting/advisory role for Astellas Pharma, AstraZeneca, Genentech/Roche, Pfizer, Eisai, Janssen Oncology, Modra Pharmaceuticals, Seattle Genetics/Astellas, Vizuri, Orion Pharma GmbH, and Novartis; and research funding from Genentech, Seattle Genetics, BioClin Therapeutics, Janssen Oncology, and Merck—all to the institution. Jose L. Perez-Gracia reports a consulting/advisory role for Bristol-Myers Squibb, Roche, Ipsen, Pierre Fabre, and Seattle Genetics; a role in the speakers’ bureau of Bristol-Myers Squibb, Roche, MSD, and Eisai; travel/accommodation/expenses from Roche, Bristol-Myers Squibb, and MSD; and research funding from Roche, Bristol-Myers Squibb, Eisai, MSD, Janssen, and Incyte—all to the institution. Jean H. Hoffman-Censits reports honoraria from Roche/Genentech and Clovis Oncology; a consulting/advisory role for Roche/Genentech, Foundation Medicine, and AstraZeneca; research funding from Sanofi; and travel/accommodation/expenses from Roche/Genentech. Michiel S. Van Der Heijden reports a consulting/advisory role for Roche/Genentech, Astellas Pharma, AstraZeneca/MedImmune, Bristol-Myers Squibb, MSD Oncology, Seattle Genetics, and Janssen—all to the institution; travel/accommodation/expenses from Novartis, Astellas Pharma, MSD Oncology, and Roche; and research funding from Astellas Pharma, Bristol-Myers Squibb, Roche, and AstraZeneca—all to the institution. Julie Pavlova reports employment and shareholding in Roche/Genentech. Lars Thiebach reports employment and shareholding in Roche Pharma AG. Sabine de Ducla reports employment and shareholding in Roche. Simon Fear reports employment by Hays Schweiz AG on behalf of Roche. Thomas Powles reports a consulting/advisory role for Genentech/Roche, Bristol-Myers Squibb, Merck, Novartis, AstraZeneca, Ipsen, Pfizer, Novartis, Incyte, and Seattle Genetics; travel/accommodation/expenses from Bristol-Myers Squibb, Pfizer, Novartis/Ipsen, MSD, Roche/Genentech, AstraZeneca, Research to Practice, and Ferring; honoraria from Roche/Genentech, Bristol-Myers Squibb, Merck, Pfizer, AstraZeneca, Novartis, Gerson Lehrman Group, Janssen R&D, Ferring, and Seattle Genetics/Astellas; and research funding from AstraZeneca/MedImmune and Roche/Genentech. Cora N. Sternberg reports consultancy for Pfizer, MSD, Merck, AstraZeneca, Astellas, Sanofi-Genzyme, Roche/Genentech, and Incyte.
Funding Information:
Funding/Support and role of the sponsor: All three trials were sponsored and funded by F. Hoffmann-La Roche Ltd, Basel, Switzerland .
Funding Information:
Acknowledgements: Medical writing assistance for this manuscript was provided by Jennifer Kelly, MA (Medi-Kelsey Ltd, Ashbourne, UK), funded by F. Hoffmann-La Roche Ltd, Basel, Switzerland. The authors would like to thank the patients participating in the trial and their families, investigators and staff at participating centres, independent data monitoring committees, and study teams at F. Hoffmann-La Roche Ltd. Qualified researchers may request access to individual patient-level data through the clinical study data request platform ( https://vivli.org/ ). Further details on Roche’s criteria for eligible studies are available at https://vivli.org/members/ourmembers/ . Further details on Roche’s Global Policy on the Sharing of Clinical Information and how to request access to related clinical study documents can be found at https://www.roche.com/research_and_development/who_we_are_how_we_work/clinical_trials/our_commitment_to_data_sharing.htm .
Publisher Copyright:
© 2020 European Association of Urology
Copyright:
Copyright 2020 Elsevier B.V., All rights reserved.
PY - 2020/11/7
Y1 - 2020/11/7
N2 - Background: The value of a complete response to immune checkpoint inhibitor treatment for urothelial cancer is well recognised, but less is known about long-term outcomes in patients with a partial response or the benefit of achieving disease stabilisation. Objective: To determine clinical outcomes in patients with a partial response or stable disease on atezolizumab therapy for advanced urinary tract carcinoma (UTC). Design, setting, and participants: Data were extracted from three prospective trials (IMvigor210 cohort 2, SAUL, and IMvigor211) evaluating single-agent atezolizumab therapy for platinum-pretreated advanced UTC. The analysis population included 604 atezolizumab-treated and 208 chemotherapy-treated patients (229 achieving a partial response and 583 achieving stable disease). Intervention: Atezolizumab 1200 mg every 3 wk until progression or unacceptable toxicity or single-agent chemotherapy for patients in the control arm of IMvigor211. Outcome measurements and statistical analysis: Baseline characteristics, treatment exposure, overall survival, duration of disease control. Partial response and stable disease populations were analysed separately. Results and limitations: The population of patients with a partial response included more patients with programmed cell death ligand 1 (PD-L1) expression on ≥5% of tumour-infiltrating immune cells than the stable disease population. The median time to best response was 2.1 mo across trials and treatments, regardless of the type of response. Atezolizumab-treated patients with a partial response had sustained disease control (median overall survival not reached); durations of disease control and overall survival were longer with atezolizumab than with chemotherapy. In patients with stable disease, median overall survival was numerically longer with atezolizumab (exceeding 1 yr) than with chemotherapy. Irrespective of treatment, durations of disease control and survival were shorter in patients with stable disease than in those achieving a partial response. These analyses are limited by their post hoc exploratory nature and relatively short follow-up. Conclusions: Stable disease and partial response are meaningful clinical outcomes in atezolizumab-treated patients with advanced UTC. Patient summary: In this report, we looked at the outcomes in patients whose tumours responded to treatment to some extent, but the tumour did not disappear completely. We aimed to understand whether a modest response to treatment was associated with meaningful long-term outcomes for patients. We found that on average, life expectancy was >1 yr in patients whose disease was stabilised and even longer in those whose tumours showed some shrinkage in response to treatment.
AB - Background: The value of a complete response to immune checkpoint inhibitor treatment for urothelial cancer is well recognised, but less is known about long-term outcomes in patients with a partial response or the benefit of achieving disease stabilisation. Objective: To determine clinical outcomes in patients with a partial response or stable disease on atezolizumab therapy for advanced urinary tract carcinoma (UTC). Design, setting, and participants: Data were extracted from three prospective trials (IMvigor210 cohort 2, SAUL, and IMvigor211) evaluating single-agent atezolizumab therapy for platinum-pretreated advanced UTC. The analysis population included 604 atezolizumab-treated and 208 chemotherapy-treated patients (229 achieving a partial response and 583 achieving stable disease). Intervention: Atezolizumab 1200 mg every 3 wk until progression or unacceptable toxicity or single-agent chemotherapy for patients in the control arm of IMvigor211. Outcome measurements and statistical analysis: Baseline characteristics, treatment exposure, overall survival, duration of disease control. Partial response and stable disease populations were analysed separately. Results and limitations: The population of patients with a partial response included more patients with programmed cell death ligand 1 (PD-L1) expression on ≥5% of tumour-infiltrating immune cells than the stable disease population. The median time to best response was 2.1 mo across trials and treatments, regardless of the type of response. Atezolizumab-treated patients with a partial response had sustained disease control (median overall survival not reached); durations of disease control and overall survival were longer with atezolizumab than with chemotherapy. In patients with stable disease, median overall survival was numerically longer with atezolizumab (exceeding 1 yr) than with chemotherapy. Irrespective of treatment, durations of disease control and survival were shorter in patients with stable disease than in those achieving a partial response. These analyses are limited by their post hoc exploratory nature and relatively short follow-up. Conclusions: Stable disease and partial response are meaningful clinical outcomes in atezolizumab-treated patients with advanced UTC. Patient summary: In this report, we looked at the outcomes in patients whose tumours responded to treatment to some extent, but the tumour did not disappear completely. We aimed to understand whether a modest response to treatment was associated with meaningful long-term outcomes for patients. We found that on average, life expectancy was >1 yr in patients whose disease was stabilised and even longer in those whose tumours showed some shrinkage in response to treatment.
UR - http://www.scopus.com/inward/record.url?scp=85097047819&partnerID=8YFLogxK
U2 - 10.1016/j.euf.2020.10.009
DO - 10.1016/j.euf.2020.10.009
M3 - Journal articles
C2 - 33168461
AN - SCOPUS:85097047819
SN - 2405-4569
JO - European urology focus
JF - European urology focus
ER -