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

Powles, T. et al. (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), pp. 48-55. (doi:10.1200/JCO.2015.66.3468) (PMID:28034079)

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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.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Jones, Professor Robert
Authors: Powles, T., Huddart, R. A., Elliott, T., Sarker, S.-J., Ackerman, C., Jones, R., Hussain, S., Crabb, S., Jagdev, S., Chester, J., Hilman, S., Beresford, M., Macdonald, G., Santhanam, S., Frew, J. A., Stockdale, A., Hughes, S., Berney, D., and Chowdhury, S.
College/School:College of Medical Veterinary and Life Sciences > Institute of Cancer Sciences
Journal Name:Journal of Clinical Oncology
Publisher:American Society of Clinical Oncology
ISSN:0732-183X
ISSN (Online):1527-7755
Published Online:31 October 2016
Copyright Holders:Copyright © 2016 American Society of Clinical Oncology
First Published:First published in Journal of Clinical Oncology 35(1): 48-55
Publisher Policy:Reproduced in accordance with the publisher copyright policy

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