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Randomized phase II study investigating Pazopanib versus weekly Paclitaxel in relapsed or progressive urothelial cancer

Randomized phase II study investigating Pazopanib versus weekly Paclitaxel in relapsed or progressive urothelial cancer
Randomized phase II study investigating Pazopanib versus weekly Paclitaxel in relapsed or progressive urothelial cancer

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/m(2) days 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.

Journal Article
1527-7755
1770-1777
Jones, Robert J.
bd215beb-7527-4479-be9a-b7df94aae7c4
Hussain, Syed A.
c08e606a-bf25-4672-b6d8-fa376e593b92
Protheroe, Andrew S.
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Birtle, Alison
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Chakraborti, Prabir
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Huddart, Robert A.
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Jagdev, Satinder
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Bahl, Amit
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Stockdale, Andrew
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Sundar, Santhanam
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Crabb, Simon J.
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Dixon-Hughes, Judith
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Alexander, Laura
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Morris, Anna
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Kelly, Caroline
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Stobo, Jon
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Paul, James
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Powles, Thomas
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Jones, Robert J.
bd215beb-7527-4479-be9a-b7df94aae7c4
Hussain, Syed A.
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Protheroe, Andrew S.
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Birtle, Alison
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Chakraborti, Prabir
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Huddart, Robert A.
4491c174-99e7-4cfe-a5c2-845be33405dc
Jagdev, Satinder
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Bahl, Amit
98bd0c14-6b4e-4d78-882e-42bfc42e7005
Stockdale, Andrew
141839be-7557-4d51-abc6-a2ad79af1978
Sundar, Santhanam
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Crabb, Simon J.
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Dixon-Hughes, Judith
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Alexander, Laura
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Morris, Anna
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Kelly, Caroline
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Stobo, Jon
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Paul, James
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Powles, Thomas
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Jones, Robert J., Hussain, Syed A., Protheroe, Andrew S., Birtle, Alison, Chakraborti, Prabir, Huddart, Robert A., Jagdev, Satinder, Bahl, Amit, Stockdale, Andrew, Sundar, Santhanam, Crabb, Simon J., Dixon-Hughes, Judith, Alexander, Laura, Morris, Anna, Kelly, Caroline, Stobo, Jon, Paul, James and Powles, Thomas (2017) Randomized phase II study investigating Pazopanib versus weekly Paclitaxel in relapsed or progressive urothelial cancer. Journal of Clinical Oncology, 35 (16), 1770-1777. (doi:10.1200/JCO.2016.70.7828).

Record type: Article

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/m(2) days 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.

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jco.2016.70.7828 - Version of Record
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Accepted/In Press date: 16 February 2017
e-pub ahead of print date: 12 April 2017
Keywords: Journal Article
Organisations: Cancer Sciences

Identifiers

Local EPrints ID: 410706
URI: http://eprints.soton.ac.uk/id/eprint/410706
ISSN: 1527-7755
PURE UUID: 8903eb5a-cc68-4dbd-a8f5-8c82a384e3da
ORCID for Simon J. Crabb: ORCID iD orcid.org/0000-0003-3521-9064

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Date deposited: 09 Jun 2017 09:23
Last modified: 16 Mar 2024 05:17

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Contributors

Author: Robert J. Jones
Author: Syed A. Hussain
Author: Andrew S. Protheroe
Author: Alison Birtle
Author: Prabir Chakraborti
Author: Robert A. Huddart
Author: Satinder Jagdev
Author: Amit Bahl
Author: Andrew Stockdale
Author: Santhanam Sundar
Author: Simon J. Crabb ORCID iD
Author: Judith Dixon-Hughes
Author: Laura Alexander
Author: Anna Morris
Author: Caroline Kelly
Author: Jon Stobo
Author: James Paul
Author: Thomas Powles

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