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.
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Authors
Powles, T
Huddart, RA
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, JA
Stockdale, A
Hughes, S
Berney, D
Chowdhury, S
Huddart, RA
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, JA
Stockdale, A
Hughes, S
Berney, D
Chowdhury, S
Document Type
Journal Article
Date
2017-01-01
Date Accepted
2016-10-31
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.
Citation
Journal of clinical oncology : official journal of the American Society of Clinical Oncology, 2017, 35 (1), pp. 48 - 55
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Source Title
Publisher
AMER SOC CLINICAL ONCOLOGY
ISSN
0732-183X
eISSN
1527-7755
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Research Team
Clinical Academic Radiotherapy (Huddart)