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.
J Clin Oncol. 2017 Jan;35(1):48-55. doi: 10.1200/JCO.2015.66.3468. Epub 2016 Oct 28.
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.
探讨一线化疗后维持使用拉帕替尼（lapatinib）治疗人表皮生长因子受体（HER）1/HER2 阳性转移性尿路上皮膀胱癌（UBC）的疗效。
对转移性 UBC 患者进行集中筛选，以检测 HER1/HER2 是否过表达。对 HER1/2 过表达且在一线/初始化疗期间未发生疾病进展（4 至 8 个周期）的患者，在完成转移性疾病的一线/初始化疗后，进行 1:1 随机分组，分别接受拉帕替尼或安慰剂治疗。主要终点为无进展生存期（PFS）。
2007 年至 2013 年期间，共有 446 例 UBC 患者接受筛查，其中 232 例 HER1 或 HER2 阳性疾病患者被随机分配。拉帕替尼和安慰剂的中位 PFS 分别为 4.5（95%CI，2.8 至 5.4）和 5.1（95%CI，3.0 至 5.8）个月（危险比，1.07；95%CI，0.81 至 1.43；P =.63）。拉帕替尼和安慰剂的总生存期分别为 12.6（95%CI，9.0 至 16.2）和 12.0（95%CI，10.5 至 14.9）个月（危险比，0.96；95%CI，0.70 至 1.31；P =.80）。因不良事件停药的比例在两组间相似（拉帕替尼组 6%，安慰剂组 5%）。拉帕替尼和安慰剂组 3 级或 4 级不良事件发生率分别为 8.6%和 8.1%（P =.82）。针对 HER1/HER2 强阳性（免疫组化 3+；n = 111）、仅 HER1 阳性（n = 102）和仅 HER2 阳性（n = 42）的患者进行的预设亚组分析显示，PFS 和总生存期均未显示拉帕替尼有显著获益（每种情况下 P >.05）。
本试验未发现一线化疗后添加维持治疗的拉帕替尼能显著改善患者的预后。
