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, Thomas, Huddart, Robert A., Elliott, Tony, Sarker, Shah-Jalal, Ackerman, Charlotte, Jones, Robert, Hussain, Syed, Crabb, Simon, Jagdev, Satinder, Chester, John ORCID: https://orcid.org/0000-0002-7830-3840, Hilman, Serena, Beresford, Mark, Macdonald, Graham, Sundar, Santhanam, 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) , pp. 48-55. 10.1200/JCO.2015.66.3468

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Abstract

Purpose: The purpose of this trial was to establish if maintenance lapatinib after first-line chemotherapy is beneficial in HER1/HER2 positive metastatic urothelial bladder cancer (UBC) patients. Method: Patients with metastatic UBC were screened centrally for HER1/HER2 over expression. HER1/2 positive screened patients, who did not have progressive disease during chemotherapy (4-8 cycles) were randomised (1:1) to lapatinib (L) or placebo (P) after completion of first line/initial chemotherapy for metastatic disease. The primary endpoint was progression free survival (PFS). Results: Between 2007-2013, 446 UBC patients were screened and 232 HER 1 or 2 positive patients were randomised. The median PFS for L and P were 4.5 months (95% CI: 2.8 – 5.4) and 5.1 months (95% CI: 3.0 – 5.8) respectively [HR: 1.07 (95% CI: 0.81 - 1.43) p = 0.63]. The overall survival for L and P were 12.6 months (95% CI: 9.0 – 16.2) and 12.0 months (95% CI: 10.5 – 14.9) respectively [HR = 0.96 (95% CI: 0.7 - 1.31) p = 0.80]. Discontinuation due to AEs were similar in both arms (6% lapatinib and 5% placebo). The rate of grade 3-4 AEs for L and P was 8.6% vs. 8.1% (p = 0.82). Pre-planned subset analysis of i) HER1/HER2 strongly positive patients (3+ on immunohistochemistry: n= 111) ii) HER1 only positive patients (n= 102) iii) HER2 only positive patients (n= 42) showed no significant benefit with lapatinib in terms of PFS and OS (p>0.05 for each). Conclusion: This trial failed to find significant improvements in outcome by the addition of maintenance lapatinib to standard of care.

Item Type:	Article
Date Type:	Publication
Status:	Published
Schools:	Medicine
Subjects:	R Medicine > RC Internal medicine > RC0254 Neoplasms. Tumors. Oncology (including Cancer) R Medicine > RM Therapeutics. Pharmacology
Publisher:	American Society of Clinical Oncology
ISSN:	0732-183X
Date of First Compliant Deposit:	20 December 2016
Date of Acceptance:	5 October 2016
Last Modified:	05 May 2023 13:03
URI:	https://orca.cardiff.ac.uk/id/eprint/96897

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