Jens Bedke1, Axel S Merseburger2, Yohann Loriot3, Daniel Castellano4, Ernest Choy5, Ignacio Duran6, Jonathan E Rosenberg7, Daniel P Petrylak8, Robert Dreicer9, Jose L Perez-Gracia10, Jean H Hoffman-Censits11, Michiel S Van Der Heijden12, Julie Pavlova13, Lars Thiebach14, Sabine de Ducla13, Simon Fear13, Thomas Powles15, Cora N Sternberg16. 1. Department of Urology, University of Tübingen, Tübingen, Germany. Electronic address: jens.bedke@med.uni-tuebingen.de. 2. Department of Urology, Campus Lübeck, University Hospital Schleswig-Holstein, Lübeck, Germany. 3. Department of Cancer Medicine and Institut National de la Santé et de la Recherche Médicale (INSERM) U981, Université Paris-Sud, Université Paris-Saclay, Gustave Roussy, Villejuif, France. 4. Medical Oncology Service, Hospital Universitario 12 de Octubre, Madrid, Spain. 5. CREATE Centre, Section of Rheumatology, Division of Infection and Immunity, Cardiff University School of Medicine, Cardiff, UK. 6. Hospital Universitario Virgen del Rocio, Seville, Spain. 7. Memorial Sloan Kettering Cancer Center, New York, NY, USA. 8. Smilow Cancer Center, Yale University, New Haven, CT, USA. 9. University of Virginia Cancer Center, Charlottesville, VA, USA. 10. Clínica Universidad de Navarra, University of Navarra, Pamplona, Navarre, Spain. 11. The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, MD, USA. 12. The Netherlands Cancer Institute, Amsterdam, The Netherlands. 13. F. Hoffmann-La Roche Ltd, Basel, Switzerland. 14. Roche Pharma AG, Grenzach-Wyhlen, Germany. 15. Barts Cancer Institute, Experimental Cancer Medicine Centre, Queen Mary University of London, St Bartholomew's Hospital, London, UK. 16. San Camillo and Forlanini Hospitals, Rome, Italy.
Abstract
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.
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.
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