Phase III, double-blind, randomized trial that compared maintenance lapatinib versus placebo after first-line chemotherapy in patients with human epidermal growth factor receptor 1/2-positive metastatic bladder cancer
Phase III, double-blind, randomized trial that compared maintenance lapatinib versus placebo after first-line chemotherapy in patients with human epidermal growth factor receptor 1/2-positive metastatic bladder cancer
Purpose: To establish whether maintenance lapatinib after first-line chemotherapy is beneficial in human epidermal growth factor receptor (HER) 1/HER2-positive metastatic urothelial bladder cancer (UBC).
Methods: Patients with metastatic UBC were screened centrally for HER1/HER2 overexpression. Patients who screened positive for HER1/2 and who did not have progressive disease during chemotherapy (four to eight cycles) were randomly assigned one to one to lapatinib or placebo after completion of first-line/initial chemotherapy for metastatic disease. The primary end point was progression-free survival (PFS).
Results: Between 2007 and 2013, 446 patients with UBC were screened, and 232 with HER1- or HER2-positive disease were randomly assigned. The median PFS for lapatinib and placebo was 4.5 (95% CI, 2.8 to 5.4) and 5.1 (95% CI, 3.0 to 5.8) months, respectively (hazard ratio, 1.07; 95% CI, 0.81 to 1.43; P = .63). The overall survival for lapatinib and placebo was 12.6 (95% CI, 9.0 to 16.2) and 12.0 (95% CI, 10.5 to 14.9) months, respectively (hazard ratio, 0.96; 95% CI, 0.70 to 1.31; P = .80). Discontinuation due to adverse events were similar in both arms (6% lapatinib and 5% placebo). The rate of grade 3 to 4 adverse events for lapatinib and placebo was 8.6% versus 8.1% ( P = .82). Preplanned subset analysis of patients strongly positive for HER1/HER2 (3+ on immunohistochemistry; n = 111), patients positive for only HER1 (n = 102), and patients positive for only HER2 (n = 42) showed no significant benefit with lapatinib in terms of PFS and overall survival ( P > .05 for each).
Conclusion This trial did not find significant improvements in outcome by the addition of maintenance lapatinib to standard of care.
Journal Article
48-55
Powles, Thomas
55539b87-1c5e-45ae-9e07-5b2232c2236c
Huddart, Robert A.
4491c174-99e7-4cfe-a5c2-845be33405dc
Elliott, Tony
494b0d76-db11-4ef0-bbdb-bd023794726a
Sarker, Shah-Jalal
5f0c81f3-6c2a-4b1c-a976-640baeee914c
Ackerman, Charlotte
d6720ccb-9499-47ba-bd46-8ad647d8a170
Jones, Robert
c8f8587e-d585-4177-bc9c-730c2e14a432
Hussain, Syed
04946d73-9bda-446a-8fd1-fc98c63e9eed
Crabb, Simon
bcd1b566-7677-4f81-8429-3ab0e85f8373
Jagdev, Satinder
a5fcb618-852f-4a09-96b0-c7afb5582163
Chester, John
c055dcc5-6b69-42e7-a61f-d5043bd3e69b
Hilman, Serena
93a63b88-ece7-4a08-8503-2d6273ea78dd
Beresford, Mark
6651ff9c-e960-46e1-b050-b97382cc24ad
Macdonald, Graham
875f03a2-b26c-4f00-a4e7-c94cd9aa85ec
Santhanam, Sundar
486f9253-baa3-4b95-a588-4f1fc6040529
Frew, John A.
53f58b0c-b0df-43a0-bc4e-d03488833525
Stockdale, Andrew
141839be-7557-4d51-abc6-a2ad79af1978
Hughes, Simon
d6203578-75f1-4c14-ac9f-c3cea0f2bad9
Berney, Daniel
54e0a217-b04f-4c5b-930c-62b0580f6ae3
Chowdhury, Simon
74cdad3c-31c9-4c77-9f24-e87debb9139e
1 January 2017
Powles, Thomas
55539b87-1c5e-45ae-9e07-5b2232c2236c
Huddart, Robert A.
4491c174-99e7-4cfe-a5c2-845be33405dc
Elliott, Tony
494b0d76-db11-4ef0-bbdb-bd023794726a
Sarker, Shah-Jalal
5f0c81f3-6c2a-4b1c-a976-640baeee914c
Ackerman, Charlotte
d6720ccb-9499-47ba-bd46-8ad647d8a170
Jones, Robert
c8f8587e-d585-4177-bc9c-730c2e14a432
Hussain, Syed
04946d73-9bda-446a-8fd1-fc98c63e9eed
Crabb, Simon
bcd1b566-7677-4f81-8429-3ab0e85f8373
Jagdev, Satinder
a5fcb618-852f-4a09-96b0-c7afb5582163
Chester, John
c055dcc5-6b69-42e7-a61f-d5043bd3e69b
Hilman, Serena
93a63b88-ece7-4a08-8503-2d6273ea78dd
Beresford, Mark
6651ff9c-e960-46e1-b050-b97382cc24ad
Macdonald, Graham
875f03a2-b26c-4f00-a4e7-c94cd9aa85ec
Santhanam, Sundar
486f9253-baa3-4b95-a588-4f1fc6040529
Frew, John A.
53f58b0c-b0df-43a0-bc4e-d03488833525
Stockdale, Andrew
141839be-7557-4d51-abc6-a2ad79af1978
Hughes, Simon
d6203578-75f1-4c14-ac9f-c3cea0f2bad9
Berney, Daniel
54e0a217-b04f-4c5b-930c-62b0580f6ae3
Chowdhury, Simon
74cdad3c-31c9-4c77-9f24-e87debb9139e
Powles, Thomas, Huddart, Robert A., Elliott, Tony, Sarker, Shah-Jalal, Ackerman, Charlotte, Jones, Robert, Hussain, Syed, Crabb, Simon, Jagdev, Satinder, Chester, John, Hilman, Serena, Beresford, Mark, Macdonald, Graham, Santhanam, Sundar, Frew, John A., Stockdale, Andrew, Hughes, Simon, Berney, Daniel and Chowdhury, Simon
(2017)
Phase III, double-blind, randomized trial that compared maintenance lapatinib versus placebo after first-line chemotherapy in patients with human epidermal growth factor receptor 1/2-positive metastatic bladder cancer.
Journal of Clinical Oncology, 35 (1), .
(doi:10.1200/JCO.2015.66.3468).
Abstract
Purpose: To establish whether maintenance lapatinib after first-line chemotherapy is beneficial in human epidermal growth factor receptor (HER) 1/HER2-positive metastatic urothelial bladder cancer (UBC).
Methods: Patients with metastatic UBC were screened centrally for HER1/HER2 overexpression. Patients who screened positive for HER1/2 and who did not have progressive disease during chemotherapy (four to eight cycles) were randomly assigned one to one to lapatinib or placebo after completion of first-line/initial chemotherapy for metastatic disease. The primary end point was progression-free survival (PFS).
Results: Between 2007 and 2013, 446 patients with UBC were screened, and 232 with HER1- or HER2-positive disease were randomly assigned. The median PFS for lapatinib and placebo was 4.5 (95% CI, 2.8 to 5.4) and 5.1 (95% CI, 3.0 to 5.8) months, respectively (hazard ratio, 1.07; 95% CI, 0.81 to 1.43; P = .63). The overall survival for lapatinib and placebo was 12.6 (95% CI, 9.0 to 16.2) and 12.0 (95% CI, 10.5 to 14.9) months, respectively (hazard ratio, 0.96; 95% CI, 0.70 to 1.31; P = .80). Discontinuation due to adverse events were similar in both arms (6% lapatinib and 5% placebo). The rate of grade 3 to 4 adverse events for lapatinib and placebo was 8.6% versus 8.1% ( P = .82). Preplanned subset analysis of patients strongly positive for HER1/HER2 (3+ on immunohistochemistry; n = 111), patients positive for only HER1 (n = 102), and patients positive for only HER2 (n = 42) showed no significant benefit with lapatinib in terms of PFS and overall survival ( P > .05 for each).
Conclusion This trial did not find significant improvements in outcome by the addition of maintenance lapatinib to standard of care.
Text
JCO.2015.66
- Version of Record
Available under License Other.
More information
Accepted/In Press date: 1 April 2016
e-pub ahead of print date: 31 October 2016
Published date: 1 January 2017
Keywords:
Journal Article
Identifiers
Local EPrints ID: 412846
URI: http://eprints.soton.ac.uk/id/eprint/412846
ISSN: 1527-7755
PURE UUID: a71fccb7-993c-4ab5-867d-54bd8cbd3132
Catalogue record
Date deposited: 02 Aug 2017 16:31
Last modified: 16 Mar 2024 05:05
Export record
Altmetrics
Contributors
Author:
Thomas Powles
Author:
Robert A. Huddart
Author:
Tony Elliott
Author:
Shah-Jalal Sarker
Author:
Charlotte Ackerman
Author:
Robert Jones
Author:
Syed Hussain
Author:
Satinder Jagdev
Author:
John Chester
Author:
Serena Hilman
Author:
Mark Beresford
Author:
Graham Macdonald
Author:
Sundar Santhanam
Author:
John A. Frew
Author:
Andrew Stockdale
Author:
Simon Hughes
Author:
Daniel Berney
Author:
Simon Chowdhury
Download statistics
Downloads from ePrints over the past year. Other digital versions may also be available to download e.g. from the publisher's website.
View more statistics