A phase II/III randomised trial comparing maintenance lapatinib vs placebo after first line chemotherapy in HER1/2 positive metastatic bladder cancer
1Barts Cancer Institute, London, UK,2Guy’s and St Thomas’ Hospital NHS Trust, London, UK,3The Christie NHS Foundation Trust, Manchester, UK,4Beatson West of Scotland Cancer Centre, Glasgow, UK,5The Clatterbridge Cancer Centre NHS Foundation Trust, Liverpool, UK,6University Hospital Southampton NHS Foundation Trust, Southampton, UK,7St James’s University Hospital, Leeds, UK,8Bristol Haematology and Oncology Centre, Bristol, UK,9Aberdeen Royal Infirmary, Aberdeen, UK,10Nottingham University Hospitals NHS Trust, Nottingham, UK,11Freeman Hospital, Newcastle, UK,12University Hospitals Coventry and Warwickshire NHS Trust, Coventry, UK,13Royal Marsden Hospital, Surrey, UK
First-line chemotherapy for metastatic transitional cell carcinoma (TCC) is associated with clinical benefit. Further therapies are largely ineffective. The purpose of this trial was to establish if maintenance lapatinib after first-line chemotherapy was associated with clinical benefit in HER1/HER2 positive TCC patients.
During first-line chemotherapy, patients were screened for their HER1/HER2 status by centralised immunohistochemistry (IHC). HER1/2 positive patients with advanced/metastatic TCC who achieved clinical benefit after completing first-line chemotherapy (4-8 cycles) were potentially eligible for randomisation (1:1). The primary endpoint was to compare progression free survival (PFS). Secondary endpoints included adverse events (AE), overall survival (OS) and subset analysis for HER status.
Between 2007-2013, 455 patients were screened and 232 HER 1 or 2 positive patients were randomised to lapatinib (L) (n = 116) or placebo (P) (n = 116). 72.5% had visceral metastasis. 60.8% received cisplatin based chemotherapy. The median number of chemotherapy cycles was 6. The progression free survival for L and P was 4.6 months (95% CI: 2.8 - 5.4) and 5.3 months (95% CI: 3.0 - 5.8) respectively [HR: 1.1 (95% CI: 0.79 - 1.39) p = 0.77]. The overall survival for L and P was 12.6 months (95% CI: 9 - 16.2) and 11.9 months (95% CI: 10.6 - 15.8) respectively [HR = 0.96 (95% CI: 0.71 - 1.31) p = 0.79). The best response rate for L and P was 13.8% vs 7.8% (p = 0.14). The rate of grade 3-4 AEs for L and P was 24.3% vs. 15.5% (p = 0.09). Subset analysis of i) HER1/HER2 3+ positive patients on IHC ii) HER1 positive patients iii) HER2 positive patients showed no significant benefit in PFS (HR 0.94, 0.99 and 1.19 respectively: p > 0.05 for each) or OS (HR 0.76, 0.92 and 1.03 respectively: p > 0.05 for each) for lapatinib. A model predicting outcomes was constructed.
This is the first personalised randomised trial in metastatic TCC. It shows maintenance lapatinib does not improve outcomes in HER1 or HER2 positive individuals.