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 of clinical oncology : official journal of the American Society of Clinical Oncology. 2016 Oct 28 [Epub]
Thomas Powles, Robert A Huddart, Tony Elliott, Shah-Jalal Sarker, Charlotte Ackerman, Robert Jones, Syed Hussain, Simon Crabb, Satinder Jagdev, John Chester, Serena Hilman, Mark Beresford, Graham Macdonald, Sundar Santhanam, John A Frew, Andrew Stockdale, Simon Hughes, Daniel Berney, Simon Chowdhury
Thomas Powles, Shah-Jalal Sarker, Charlotte Ackerman, and Daniel Berney, Queen Mary University of London; Simon Hughes and Simon Chowdhury, Guy's and St Thomas' National Health Service (NHS) Foundation Trust, London; Robert A. Huddart, Institute of Cancer Research, Sutton; Tony Elliott, Christie Hospital NHS Foundation Trust, Manchester; Robert Jones, University of Glasgow, Glasgow; Syed Hussain, University of Liverpool, Liverpool; Simon Crabb, University of Southampton, Southampton; Satinder Jagdev, St James's University Hospital, Leeds; John Chester, Cardiff University, Cardiff; Serena Hilman, Bristol Haematology and Oncology Centre, Bristol; Mark Beresford, Royal United Hospitals Bath, Bath; Graham Macdonald, Aberdeen Royal Infirmary, Aberdeen; Sundar Santhanam, Nottingham University Hospitals NHS Trust, Nottingham; John A. Frew, Northern Centre for Cancer Care, Newcastle upon Tyne; and Andrew Stockdale, University Hospital, Coventry, United Kingdom.