Powles, T;
Huddart, RA;
Elliott, T;
Sarker, S-J;
Ackerman, C;
Jones, R;
Hussain, S;
... Chowdhury, S; + view all
(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.
10.1200/JCO.2015.66.3468.
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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.
| Type: | Article |
|---|---|
| Title: | 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 |
| Location: | United States |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1200/JCO.2015.66.3468 |
| Publisher version: | https://doi.org/10.1200/JCO.2015.66.3468 |
| Language: | English |
| Additional information: | This is the published version of record. For information on re-use, please refer to the publisher’s terms and conditions. |
| Keywords: | Aged, Antineoplastic Combined Chemotherapy Protocols, Carcinoma, Transitional Cell, Cisplatin, Disease-Free Survival, Double-Blind Method, Female, Humans, Maintenance Chemotherapy, Male, Middle Aged, Quinazolines, Receptor, Epidermal Growth Factor, Receptor, ErbB-2, Response Evaluation Criteria in Solid Tumors, Urinary Bladder Neoplasms |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10060659 |
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