Trastuzumab Plus Anastrozole Versus Anastrozole Alone for the Treatment of Postmenopausal Women With Human Epidermal Growth Factor Receptor 2-Positive, Hormone Receptor-Positive Metastatic Breast Cancer: Results From the Randomized Phase III TAnDEM Study
Trastuzumab Plus Anastrozole Versus Anastrozole Alone for the Treatment of Postmenopausal Women With Human Epidermal Growth Factor Receptor 2-Positive, Hormone Receptor-Positive Metastatic Breast Cancer: Results From the Randomized Phase III TAnDEM Study
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DOI：
10.1200/jco.2008.20.6847
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发表时间：
2009-11-20
影响因子：
45.3
通讯作者：
Jones, Alison
中科院分区：
文献类型：
--
作者：
Kaufman, Bella;Mackey, John R.;Jones, Alison
目的TAnDEM是第一个联合收割机和曲妥珠单抗联合化疗治疗人表皮生长因子受体2（HER 2）/激素受体阳性转移性乳腺癌（MBC）的随机III期临床研究（1 mg/d口服）联合或不联合曲妥珠单抗（第1天4 mg/kg静脉输注，然后每周2 mg/kg），直至进展。主要终点是意向治疗population.ResultsOverall的无进展生存期（PFS），103例患者接受曲妥珠单抗加阿那曲唑; 104只接受阿那曲唑。与接受阿那曲唑单药治疗的患者相比，曲妥珠单抗+阿那曲唑组患者的PFS显著改善（风险比= 0.63; 95% CI，0.47 - 0.84;中位PFS，4.8 vs 2.4个月;对数秩P = 0.0016）。在中心实验室确认的激素受体阳性患者（n = 150）中，曲妥珠单抗+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P = 0.006）。总体和中心实验室确认的激素受体阳性人群的总生存期显示无统计学显著性治疗差异;然而，阿那曲唑单药治疗组70%的患者在阿那曲唑单药治疗进展后交叉接受曲妥珠单抗治疗。曲妥珠单抗联合阿那曲唑组3级和4级不良事件的发生率分别为23%和5%，单用阿那曲唑组分别为15%和1%;联合组中的一名患者经历了纽约心脏协会II级充血性心力衰竭。结论与单独使用阿那曲唑相比，曲妥珠单抗联合阿那曲唑改善了HER 2/激素受体共阳性MBC患者的预后，尽管不良事件和严重不良事件在联合用药中更常见。
PurposeTAnDEM 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).Patients and MethodsPostmenopausal 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.ResultsOverall, 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.ConclusionTrastuzumab 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.