Outcomes With First-line PD-1/PD-L1 Inhibition in Advanced Urothelial Cancer: A Single Institution Experience |
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| Affiliation: | 1. School of Medicine, New York University, New York, NY;2. Department of Population Health, New York University, New York, NY;3. Perlmutter Cancer Center, New York University, New York, NY;1. College of Medicine and Public Health, Flinders University, Adelaide, Australia;2. Department of Medical Oncology, Flinders Centre for Innovation in Cancer, Flinders Medical Centre, Adelaide, Australia;1. Division of Hematology/Oncology, Abramson Cancer Center, University of Pennsylvania, Philadelphia, PA;2. Department of Radiation Oncology, Abramson Cancer Center, University of Pennsylvania, Philadelphia, PA;3. Center for Clinical Epidemiology and Biostatistics (CCEB), University of Pennsylvania, Philadelphia, PA;1. Department of Medical Oncology, AOU Ospedali Riuniti, Università Politecnica delle Marche, Ancona, Italy;2. Cancer Sciences Unit, University of Southampton, Southampton, UK;3. Dipartimento di Scienze Cliniche Specialistiche ed Odontostomatologiche, Clinica di Urologia, AOU Ospedali Riuniti, Università Politecnica delle Marche, Ancona, Italy;4. Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Meldola, Italy;5. NIHR Wellcome Trust Clinical Research Facility, University of Southampton, Southampton, UK;1. City of Hope Comprehensive Cancer Center, Duarte, CA, USA;2. Sidney Kimmel Cancer Center at Jefferson, Philadelphia, PA, USA;3. Genentech, Inc., South San Francisco, CA, USA;4. Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA;1. Barts Cancer Institute, Experimental Cancer Medicine Centre, Queen Mary University of London, St Bartholomew''s Hospital, London, UK;2. Institute of Biomedicine of Seville (IBiS), Hospital Universitario Virgen del Rocío/CSIC/Universidad de Sevilla, Seville, Spain;3. Institute of Biomedicine of Seville, Seville, Spain;4. Department of Medical Oncology, Netherlands Cancer Institute, Amsterdam, Netherlands;5. Département de Médecine Oncologique, Université Paris-Saclay, Gustave Roussy, Villejuif, France;6. US Oncology Research, Comprehensive Cancer Centers of Nevada, Las Vegas, NV, USA;7. Istituto Scientifico Romagnolo per lo studio e la Cura dei Tumori IRST IRCCS, Meldola, Italy;8. Oncology Department, European Georges Pompidou Hospital, René Descartes University, Paris, France;9. Department of Urology, Klinikum rechts der Isar, Technical University Munich, Munich, Germany;10. University Hospital 12 de Octubre, Medical Oncology Department CIBER-ONC, Madrid, Spain;11. National and Kapodistrian University of Athens Alexandra Hospital, Athens, Greece;12. Centre Léon Bérard, Lyon, France;13. Department of Cancer Medicine, Institut Paoli Calmette, Marseille, France;14. Plymouth University, Peninsula Schools of Medicine and Dentistry, Plymouth University Hospitals NHS Trust, Plymouth, UK;15. Department of Medical Oncology, Toranomon Hospital, Tokyo, Japan;p. Genentech, South San Francisco, CA, USA;q. Department of Medical Oncology, Bordeaux University Hospital, Bordeaux, France;1. Clínica Universidad de Navarra, Pamplona, Spain;2. Gustave Roussy, Université Paris-Saclay, Département de Médecine, Villejuif, France;3. Memorial Sloan Kettering Cancer Center, New York, NY, USA;4. Barts Cancer Institute, Queen Mary University of London, London, UK;5. Fondazione IRCCS, Istituto Nazionale dei Tumori, Milan, Italy;6. Plymouth University, Peninsula Schools of Medicine and Dentistry, Plymouth University Hospitals NHS Trust, Devon, UK;7. Vall d’Hebron Institute of Oncology, Vall d’Hebron University Hospital, Universitat Autonoma de Barcelona, Barcelona, Spain;8. Urologische Klinik und Poliklinik, Technical University Munich, Munich, Germany;9. Department of Urology, Medical Faculty, Heinrich Heine University Düsseldorf, Düsseldorf, Germany;10. Instituto de Biomedicina de Sevilla, IBiS/Hospital Universitario Virgen del Rocío/CSIC/Universidad de Sevilla, Sevilla, Spain;11. Department of Oncology, Hôpital Foch, Suresnes, France;12. Hospital Universitario Ramón y Cajal, Madrid, Spain;13. Genentech, Inc., South San Francisco, CA, USA;14. Netherlands Cancer Institute, Amsterdam, the Netherlands |
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| Abstract: | BackgroundFirst-line PD-inhibition in cisplatin-ineligible patients with locally advanced or metastatic urothelial cancer represents a novel clinical setting, with uncertainty concerning second-line outcomes. Specifying second-line treatment and outcomes will provide guidance in this new sequence. We performed a retrospective chart review to document the outcomes of these patients treated at our institution.Patients and MethodsOur cohort consisted of 43 patients with advanced urothelial cancer receiving first-line checkpoint inhibition. Baseline factors, programmed death-ligand 1 (PD-L1) status, treatments, and outcomes during and beyond the first line were obtained. Response was scored using Response Evaluation Criteria in Solid Tumors, version 1.1 criteria. Log rank tests were used to compare outcomes in prognostic subgroups, and outcome associations with PD-L1 status were analyzed with Fisher exact tests.ResultsA total of 43 patients received first-line atezolizumab or pembrolizumab from June 2014 until June 2018. The median age was 76.8 years, and the population was 74% male, with 60% having visceral metastases. Reasons for cisplatin ineligibility were Eastern Cooperative Oncology Group performance status 2%, 30%; renal insufficiency, 44%, and both, 21%. First-line objective response rate (ORR) was 30%, and complete response was 14%. The median overall survival was 11.7 months. Of 29 patients progressing, 17 received second-line treatment (most commonly, gemcitabine/carboplatin [10 patients]). The second-line response rate was 33%, and the ORR was 11%. The second-line median overall survival was 6.2 months. No association was found between PD-L1 status and outcomes.ConclusionOutcomes with first-line immunotherapy are consistent with historical outcomes. The ORR after first-line checkpoint inhibition falls short of historical comparators; however, the response rate compares favorably to those of chemotherapies used in previous second-line regimens. The older age and poorer performance status may have contributed to second-line outcomes. |
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| Keywords: | Bladder cancer Checkpoint inhibition Cisplatin-ineligible Immunotherapy Second-line outcomes |
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