Chaim Sheba Medical Center, Tel Hashomer, Israel.
J Clin Oncol. 2009 Nov 20;27(33):5529-37. doi: 10.1200/JCO.2008.20.6847. Epub 2009 Sep 28.
TAnDEM is the first randomized phase III study to combine a hormonal agent and trastuzumab without chemotherapy as treatment for human epidermal growth factor receptor 2 (HER2)/hormone receptor-copositive metastatic breast cancer (MBC).
Postmenopausal women with HER2/hormone receptor-copositive MBC were randomly assigned to anastrozole (1 mg/d orally) with or without trastuzumab (4 mg/kg intravenous infusion on day 1, then 2 mg/kg every week) until progression. The primary end point was progression-free survival (PFS) in the intent-to-treat population. Results Overall, 103 patients received trastuzumab plus anastrozole; 104 received anastrozole alone. Patients in the trastuzumab plus anastrozole arm experienced significant improvements in PFS compared with patients receiving anastrozole alone (hazard ratio = 0.63; 95% CI, 0.47 to 0.84; median PFS, 4.8 v 2.4 months; log-rank P = .0016). In patients with centrally confirmed hormone receptor positivity (n = 150), median PFS was 5.6 and 3.8 months in the trastuzumab plus anastrozole and anastrozole alone arms, respectively (log-rank P = .006). Overall survival in the overall and centrally confirmed hormone receptor-positive populations showed no statistically significant treatment difference; however, 70% of patients in the anastrozole alone arm crossed over to receive trastuzumab after progression on anastrozole alone. Incidence of grade 3 and 4 adverse events was 23% and 5%, respectively, in the trastuzumab plus anastrozole arm, and 15% and 1%, respectively, in the anastrozole alone arm; one patient in the combination arm experienced New York Heart Association class II congestive heart failure.
Trastuzumab plus anastrozole improves outcomes for patients with HER2/hormone receptor-copositive MBC compared with anastrozole alone, although adverse events and serious adverse events were more frequent with the combination.
TAnDEM 是首个将激素药物与曲妥珠单抗联合应用于未经化疗的人表皮生长因子受体 2（HER2）/激素受体阳性转移性乳腺癌（MBC）的随机 III 期研究。
HER2/激素受体阳性 MBC 绝经后女性患者随机接受阿那曲唑（1 毫克/天口服）联合或不联合曲妥珠单抗（第 1 天静脉输注 4 毫克/千克，然后每周 2 毫克/千克），直至疾病进展。主要终点为意向治疗人群的无进展生存期（PFS）。
共有 103 例患者接受曲妥珠单抗联合阿那曲唑治疗，104 例患者接受阿那曲唑单药治疗。与接受阿那曲唑单药治疗的患者相比，曲妥珠单抗联合阿那曲唑治疗组的患者 PFS 显著改善（风险比=0.63；95%CI，0.47 至 0.84；中位 PFS，4.8 个月对 2.4 个月；对数秩检验 P=0.0016）。在经中心确认的激素受体阳性患者（n=150）中，曲妥珠单抗联合阿那曲唑组和阿那曲唑单药组的中位 PFS 分别为 5.6 个月和 3.8 个月（对数秩检验 P=0.006）。总体和经中心确认的激素受体阳性人群的总生存期未显示出统计学显著的治疗差异；然而，阿那曲唑单药组中有 70%的患者在单独使用阿那曲唑后进展时交叉接受了曲妥珠单抗治疗。曲妥珠单抗联合阿那曲唑组中 3 级和 4 级不良事件的发生率分别为 23%和 5%，阿那曲唑单药组中分别为 15%和 1%；联合组中有 1 例患者发生纽约心脏协会（NYHA）Ⅱ级充血性心力衰竭。
与阿那曲唑单药治疗相比，曲妥珠单抗联合阿那曲唑可改善 HER2/激素受体阳性 MBC 患者的结局，尽管联合治疗组的不良事件和严重不良事件更为常见。
