title: Randomized Phase II Study Investigating Pazopanib Versus Weekly Paclitaxel in Relapsed or Progressive Urothelial Cancer.
abstract: Purpose Two previous single-arm trials have drawn conflicting conclusions regarding the activity of pazopanib in urothelial cancers after failure of platinum-based chemotherapy. Patients and Methods This randomized (1:1) open-label phase II trial compared the efficacy of pazopanib 800 mg orally with paclitaxel (80 mg/m2days 1, 8, and 15 every 28 days) in the second-line setting. The primary end point was overall survival (OS). Results Between August 2012 and October 2014, 131 patients, out of 140 planned, were randomly assigned. The study was terminated early on the recommendation of the independent data monitoring committee because of futility. Final analysis after the preplanned number of deaths (n = 110) occurred after a median follow-up of 18 months. One hundred fifteen deaths had occurred at the final data extract presented here. Median OS was 8.0 months for paclitaxel (80% CI, 6.9 to 9.7 months) and 4.7 months for pazopanib (80% CI, 4.2 to 6.4 months). The hazard ratio (HR) adjusted for baseline stratification factors was 1.28 (80% CI, 0.99 to 1.67; one-sided P = .89). Median progression-free survival was 4.1 months for paclitaxel (80% CI, 3.0 to 5.6 months) and 3.1 months for pazopanib (80% CI, 2.7 to 4.6 months; HR, 1.09; 80% CI, 0.85 to 1.40; one-sided P = .67). Discontinuations for toxicity occurred in 7.8% and 23.1% for paclitaxel and pazopanib, respectively. Conclusion Pazopanib did not have greater efficacy than paclitaxel in the second-line treatment of urothelial cancers. There was a trend toward superior OS for paclitaxel.
authors.affiliation: Robert J. Jones, Judith Dixon-Hughes, Laura Alexander, Anna Morris, Caroline Kelly, Jon Stobo, and James Paul, University of Glasgow, Glasgow; Syed A. Hussain, University of Liverpool, Liverpool; Andrew S. Protheroe, Churchill Hospital, Oxford; Alison Birtle, Royal Preston Hospital, Preston; Prabir Chakraborti, Royal Derby Hospital, Derby; Robert A. Huddart, Institute of Cancer Research, Sutton; Satinder Jagdev, St James's University Hospital, Leeds; Amit Bahl, Bristol Haematology and Oncology Centre, Bristol; Andrew Stockdale, University Hospital, Coventry; Santhanam Sundar, Nottingham University Hospitals National Health Service Trust, Nottingham; Simon J. Crabb, University of Southampton, Southampton; and Thomas Powles, Queen Mary University of London, London, United Kingdom.
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Jones
authors.affiliation: Robert J. Jones, Judith Dixon-Hughes, Laura Alexander, Anna Morris, Caroline Kelly, Jon Stobo, and James Paul, University of Glasgow, Glasgow; Syed A. Hussain, University of Liverpool, Liverpool; Andrew S. Protheroe, Churchill Hospital, Oxford; Alison Birtle, Royal Preston Hospital, Preston; Prabir Chakraborti, Royal Derby Hospital, Derby; Robert A. Huddart, Institute of Cancer Research, Sutton; Satinder Jagdev, St James's University Hospital, Leeds; Amit Bahl, Bristol Haematology and Oncology Centre, Bristol; Andrew Stockdale, University Hospital, Coventry; Santhanam Sundar, Nottingham University Hospitals National Health Service Trust, Nottingham; Simon J. Crabb, University of Southampton, Southampton; and Thomas Powles, Queen Mary University of London, London, United Kingdom.
authors.forename: Syed A
authors.initials: SA
authors.lastname: Hussain
authors.affiliation: Robert J. Jones, Judith Dixon-Hughes, Laura Alexander, Anna Morris, Caroline Kelly, Jon Stobo, and James Paul, University of Glasgow, Glasgow; Syed A. Hussain, University of Liverpool, Liverpool; Andrew S. Protheroe, Churchill Hospital, Oxford; Alison Birtle, Royal Preston Hospital, Preston; Prabir Chakraborti, Royal Derby Hospital, Derby; Robert A. Huddart, Institute of Cancer Research, Sutton; Satinder Jagdev, St James's University Hospital, Leeds; Amit Bahl, Bristol Haematology and Oncology Centre, Bristol; Andrew Stockdale, University Hospital, Coventry; Santhanam Sundar, Nottingham University Hospitals National Health Service Trust, Nottingham; Simon J. Crabb, University of Southampton, Southampton; and Thomas Powles, Queen Mary University of London, London, United Kingdom.
authors.forename: Andrew S
authors.initials: AS
authors.lastname: Protheroe
authors.affiliation: Robert J. Jones, Judith Dixon-Hughes, Laura Alexander, Anna Morris, Caroline Kelly, Jon Stobo, and James Paul, University of Glasgow, Glasgow; Syed A. Hussain, University of Liverpool, Liverpool; Andrew S. Protheroe, Churchill Hospital, Oxford; Alison Birtle, Royal Preston Hospital, Preston; Prabir Chakraborti, Royal Derby Hospital, Derby; Robert A. Huddart, Institute of Cancer Research, Sutton; Satinder Jagdev, St James's University Hospital, Leeds; Amit Bahl, Bristol Haematology and Oncology Centre, Bristol; Andrew Stockdale, University Hospital, Coventry; Santhanam Sundar, Nottingham University Hospitals National Health Service Trust, Nottingham; Simon J. Crabb, University of Southampton, Southampton; and Thomas Powles, Queen Mary University of London, London, United Kingdom.
authors.forename: Alison
authors.initials: A
authors.lastname: Birtle
authors.affiliation: Robert J. Jones, Judith Dixon-Hughes, Laura Alexander, Anna Morris, Caroline Kelly, Jon Stobo, and James Paul, University of Glasgow, Glasgow; Syed A. Hussain, University of Liverpool, Liverpool; Andrew S. Protheroe, Churchill Hospital, Oxford; Alison Birtle, Royal Preston Hospital, Preston; Prabir Chakraborti, Royal Derby Hospital, Derby; Robert A. Huddart, Institute of Cancer Research, Sutton; Satinder Jagdev, St James's University Hospital, Leeds; Amit Bahl, Bristol Haematology and Oncology Centre, Bristol; Andrew Stockdale, University Hospital, Coventry; Santhanam Sundar, Nottingham University Hospitals National Health Service Trust, Nottingham; Simon J. Crabb, University of Southampton, Southampton; and Thomas Powles, Queen Mary University of London, London, United Kingdom.
authors.forename: Prabir
authors.initials: P
authors.lastname: Chakraborti
authors.affiliation: Robert J. Jones, Judith Dixon-Hughes, Laura Alexander, Anna Morris, Caroline Kelly, Jon Stobo, and James Paul, University of Glasgow, Glasgow; Syed A. Hussain, University of Liverpool, Liverpool; Andrew S. Protheroe, Churchill Hospital, Oxford; Alison Birtle, Royal Preston Hospital, Preston; Prabir Chakraborti, Royal Derby Hospital, Derby; Robert A. Huddart, Institute of Cancer Research, Sutton; Satinder Jagdev, St James's University Hospital, Leeds; Amit Bahl, Bristol Haematology and Oncology Centre, Bristol; Andrew Stockdale, University Hospital, Coventry; Santhanam Sundar, Nottingham University Hospitals National Health Service Trust, Nottingham; Simon J. Crabb, University of Southampton, Southampton; and Thomas Powles, Queen Mary University of London, London, United Kingdom.
authors.forename: Robert A
authors.initials: RA
authors.lastname: Huddart
authors.affiliation: Robert J. Jones, Judith Dixon-Hughes, Laura Alexander, Anna Morris, Caroline Kelly, Jon Stobo, and James Paul, University of Glasgow, Glasgow; Syed A. Hussain, University of Liverpool, Liverpool; Andrew S. Protheroe, Churchill Hospital, Oxford; Alison Birtle, Royal Preston Hospital, Preston; Prabir Chakraborti, Royal Derby Hospital, Derby; Robert A. Huddart, Institute of Cancer Research, Sutton; Satinder Jagdev, St James's University Hospital, Leeds; Amit Bahl, Bristol Haematology and Oncology Centre, Bristol; Andrew Stockdale, University Hospital, Coventry; Santhanam Sundar, Nottingham University Hospitals National Health Service Trust, Nottingham; Simon J. Crabb, University of Southampton, Southampton; and Thomas Powles, Queen Mary University of London, London, United Kingdom.
authors.forename: Satinder
authors.initials: S
authors.lastname: Jagdev
authors.affiliation: Robert J. Jones, Judith Dixon-Hughes, Laura Alexander, Anna Morris, Caroline Kelly, Jon Stobo, and James Paul, University of Glasgow, Glasgow; Syed A. Hussain, University of Liverpool, Liverpool; Andrew S. Protheroe, Churchill Hospital, Oxford; Alison Birtle, Royal Preston Hospital, Preston; Prabir Chakraborti, Royal Derby Hospital, Derby; Robert A. Huddart, Institute of Cancer Research, Sutton; Satinder Jagdev, St James's University Hospital, Leeds; Amit Bahl, Bristol Haematology and Oncology Centre, Bristol; Andrew Stockdale, University Hospital, Coventry; Santhanam Sundar, Nottingham University Hospitals National Health Service Trust, Nottingham; Simon J. Crabb, University of Southampton, Southampton; and Thomas Powles, Queen Mary University of London, London, United Kingdom.
authors.forename: Amit
authors.initials: A
authors.lastname: Bahl
authors.affiliation: Robert J. Jones, Judith Dixon-Hughes, Laura Alexander, Anna Morris, Caroline Kelly, Jon Stobo, and James Paul, University of Glasgow, Glasgow; Syed A. Hussain, University of Liverpool, Liverpool; Andrew S. Protheroe, Churchill Hospital, Oxford; Alison Birtle, Royal Preston Hospital, Preston; Prabir Chakraborti, Royal Derby Hospital, Derby; Robert A. Huddart, Institute of Cancer Research, Sutton; Satinder Jagdev, St James's University Hospital, Leeds; Amit Bahl, Bristol Haematology and Oncology Centre, Bristol; Andrew Stockdale, University Hospital, Coventry; Santhanam Sundar, Nottingham University Hospitals National Health Service Trust, Nottingham; Simon J. Crabb, University of Southampton, Southampton; and Thomas Powles, Queen Mary University of London, London, United Kingdom.
authors.forename: Andrew
authors.initials: A
authors.lastname: Stockdale
authors.affiliation: Robert J. Jones, Judith Dixon-Hughes, Laura Alexander, Anna Morris, Caroline Kelly, Jon Stobo, and James Paul, University of Glasgow, Glasgow; Syed A. Hussain, University of Liverpool, Liverpool; Andrew S. Protheroe, Churchill Hospital, Oxford; Alison Birtle, Royal Preston Hospital, Preston; Prabir Chakraborti, Royal Derby Hospital, Derby; Robert A. Huddart, Institute of Cancer Research, Sutton; Satinder Jagdev, St James's University Hospital, Leeds; Amit Bahl, Bristol Haematology and Oncology Centre, Bristol; Andrew Stockdale, University Hospital, Coventry; Santhanam Sundar, Nottingham University Hospitals National Health Service Trust, Nottingham; Simon J. Crabb, University of Southampton, Southampton; and Thomas Powles, Queen Mary University of London, London, United Kingdom.
authors.forename: Santhanam
authors.initials: S
authors.lastname: Sundar
authors.affiliation: Robert J. Jones, Judith Dixon-Hughes, Laura Alexander, Anna Morris, Caroline Kelly, Jon Stobo, and James Paul, University of Glasgow, Glasgow; Syed A. Hussain, University of Liverpool, Liverpool; Andrew S. Protheroe, Churchill Hospital, Oxford; Alison Birtle, Royal Preston Hospital, Preston; Prabir Chakraborti, Royal Derby Hospital, Derby; Robert A. Huddart, Institute of Cancer Research, Sutton; Satinder Jagdev, St James's University Hospital, Leeds; Amit Bahl, Bristol Haematology and Oncology Centre, Bristol; Andrew Stockdale, University Hospital, Coventry; Santhanam Sundar, Nottingham University Hospitals National Health Service Trust, Nottingham; Simon J. Crabb, University of Southampton, Southampton; and Thomas Powles, Queen Mary University of London, London, United Kingdom.
authors.forename: Simon J
authors.initials: SJ
authors.lastname: Crabb
authors.affiliation: Robert J. Jones, Judith Dixon-Hughes, Laura Alexander, Anna Morris, Caroline Kelly, Jon Stobo, and James Paul, University of Glasgow, Glasgow; Syed A. Hussain, University of Liverpool, Liverpool; Andrew S. Protheroe, Churchill Hospital, Oxford; Alison Birtle, Royal Preston Hospital, Preston; Prabir Chakraborti, Royal Derby Hospital, Derby; Robert A. Huddart, Institute of Cancer Research, Sutton; Satinder Jagdev, St James's University Hospital, Leeds; Amit Bahl, Bristol Haematology and Oncology Centre, Bristol; Andrew Stockdale, University Hospital, Coventry; Santhanam Sundar, Nottingham University Hospitals National Health Service Trust, Nottingham; Simon J. Crabb, University of Southampton, Southampton; and Thomas Powles, Queen Mary University of London, London, United Kingdom.
authors.forename: Judith
authors.initials: J
authors.lastname: Dixon-Hughes
authors.affiliation: Robert J. Jones, Judith Dixon-Hughes, Laura Alexander, Anna Morris, Caroline Kelly, Jon Stobo, and James Paul, University of Glasgow, Glasgow; Syed A. Hussain, University of Liverpool, Liverpool; Andrew S. Protheroe, Churchill Hospital, Oxford; Alison Birtle, Royal Preston Hospital, Preston; Prabir Chakraborti, Royal Derby Hospital, Derby; Robert A. Huddart, Institute of Cancer Research, Sutton; Satinder Jagdev, St James's University Hospital, Leeds; Amit Bahl, Bristol Haematology and Oncology Centre, Bristol; Andrew Stockdale, University Hospital, Coventry; Santhanam Sundar, Nottingham University Hospitals National Health Service Trust, Nottingham; Simon J. Crabb, University of Southampton, Southampton; and Thomas Powles, Queen Mary University of London, London, United Kingdom.
authors.forename: Laura
authors.initials: L
authors.lastname: Alexander
authors.affiliation: Robert J. Jones, Judith Dixon-Hughes, Laura Alexander, Anna Morris, Caroline Kelly, Jon Stobo, and James Paul, University of Glasgow, Glasgow; Syed A. Hussain, University of Liverpool, Liverpool; Andrew S. Protheroe, Churchill Hospital, Oxford; Alison Birtle, Royal Preston Hospital, Preston; Prabir Chakraborti, Royal Derby Hospital, Derby; Robert A. Huddart, Institute of Cancer Research, Sutton; Satinder Jagdev, St James's University Hospital, Leeds; Amit Bahl, Bristol Haematology and Oncology Centre, Bristol; Andrew Stockdale, University Hospital, Coventry; Santhanam Sundar, Nottingham University Hospitals National Health Service Trust, Nottingham; Simon J. Crabb, University of Southampton, Southampton; and Thomas Powles, Queen Mary University of London, London, United Kingdom.
authors.forename: Anna
authors.initials: A
authors.lastname: Morris
authors.affiliation: Robert J. Jones, Judith Dixon-Hughes, Laura Alexander, Anna Morris, Caroline Kelly, Jon Stobo, and James Paul, University of Glasgow, Glasgow; Syed A. Hussain, University of Liverpool, Liverpool; Andrew S. Protheroe, Churchill Hospital, Oxford; Alison Birtle, Royal Preston Hospital, Preston; Prabir Chakraborti, Royal Derby Hospital, Derby; Robert A. Huddart, Institute of Cancer Research, Sutton; Satinder Jagdev, St James's University Hospital, Leeds; Amit Bahl, Bristol Haematology and Oncology Centre, Bristol; Andrew Stockdale, University Hospital, Coventry; Santhanam Sundar, Nottingham University Hospitals National Health Service Trust, Nottingham; Simon J. Crabb, University of Southampton, Southampton; and Thomas Powles, Queen Mary University of London, London, United Kingdom.
authors.forename: Caroline
authors.initials: C
authors.lastname: Kelly
authors.affiliation: Robert J. Jones, Judith Dixon-Hughes, Laura Alexander, Anna Morris, Caroline Kelly, Jon Stobo, and James Paul, University of Glasgow, Glasgow; Syed A. Hussain, University of Liverpool, Liverpool; Andrew S. Protheroe, Churchill Hospital, Oxford; Alison Birtle, Royal Preston Hospital, Preston; Prabir Chakraborti, Royal Derby Hospital, Derby; Robert A. Huddart, Institute of Cancer Research, Sutton; Satinder Jagdev, St James's University Hospital, Leeds; Amit Bahl, Bristol Haematology and Oncology Centre, Bristol; Andrew Stockdale, University Hospital, Coventry; Santhanam Sundar, Nottingham University Hospitals National Health Service Trust, Nottingham; Simon J. Crabb, University of Southampton, Southampton; and Thomas Powles, Queen Mary University of London, London, United Kingdom.
authors.forename: Jon
authors.initials: J
authors.lastname: Stobo
authors.affiliation: Robert J. Jones, Judith Dixon-Hughes, Laura Alexander, Anna Morris, Caroline Kelly, Jon Stobo, and James Paul, University of Glasgow, Glasgow; Syed A. Hussain, University of Liverpool, Liverpool; Andrew S. Protheroe, Churchill Hospital, Oxford; Alison Birtle, Royal Preston Hospital, Preston; Prabir Chakraborti, Royal Derby Hospital, Derby; Robert A. Huddart, Institute of Cancer Research, Sutton; Satinder Jagdev, St James's University Hospital, Leeds; Amit Bahl, Bristol Haematology and Oncology Centre, Bristol; Andrew Stockdale, University Hospital, Coventry; Santhanam Sundar, Nottingham University Hospitals National Health Service Trust, Nottingham; Simon J. Crabb, University of Southampton, Southampton; and Thomas Powles, Queen Mary University of London, London, United Kingdom.
authors.forename: James
authors.initials: J
authors.lastname: Paul
authors.affiliation: Robert J. Jones, Judith Dixon-Hughes, Laura Alexander, Anna Morris, Caroline Kelly, Jon Stobo, and James Paul, University of Glasgow, Glasgow; Syed A. Hussain, University of Liverpool, Liverpool; Andrew S. Protheroe, Churchill Hospital, Oxford; Alison Birtle, Royal Preston Hospital, Preston; Prabir Chakraborti, Royal Derby Hospital, Derby; Robert A. Huddart, Institute of Cancer Research, Sutton; Satinder Jagdev, St James's University Hospital, Leeds; Amit Bahl, Bristol Haematology and Oncology Centre, Bristol; Andrew Stockdale, University Hospital, Coventry; Santhanam Sundar, Nottingham University Hospitals National Health Service Trust, Nottingham; Simon J. Crabb, University of Southampton, Southampton; and Thomas Powles, Queen Mary University of London, London, United Kingdom.
authors.forename: Thomas
authors.initials: T
authors.lastname: Powles
mesh_terms: D000284:Administration, Oral; D000368:Aged; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D007191:Indazoles; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D017239:Paclitaxel / Q000008:administration & dosage*; D011743:Pyrimidines / Q000008:administration & dosage*; D013449:Sulfonamides / Q000008:administration & dosage*; D015996:Survival Rate; D014571:Urologic Neoplasms / Q000188:drug therapy*
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D007191:Indazoles; D011743:Pyrimidines; D013449:Sulfonamides; C516667:pazopanib; D017239:Paclitaxel