Palbociclib and Letrozole in Advanced Breast Cancer
Palbociclib and Letrozole in Advanced Breast Cancer
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DOI：
10.1056/nejmoa1607303
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发表时间：
2016-11-17
影响因子：
158.5
通讯作者：
Slamon, Dennis J.
中科院分区：
文献类型：
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作者：
Finn, Richard S.;Martin, Miguel;Slamon, Dennis J.
背景 一项 2 期研究表明，在雌激素受体 (ER) 阳性、人表皮生长因子受体 2 (HER2) 阴性晚期乳腺癌绝经后女性的初始治疗中，哌柏西利联合来曲唑的无进展生存期比单独使用来曲唑更长。我们进行了一项 3 期研究，旨在确认和扩大 palbociclib 加来曲唑治疗该适应症的疗效和安全性数据。 方法在这项双盲研究中，我们以 2:1 的比例随机分配 666 名患有 ER 阳性、HER2 阴性乳腺癌且既往未接受过晚期疾病治疗的绝经后女性接受 palbociclib 加来曲唑或安慰剂加来曲唑治疗。主要终点是研究人员评估的无进展生存期；次要终点是总生存期、客观缓解、临床获益反应、患者报告的结果、药代动力学效应和安全性。 结果 哌柏西利-来曲唑组的中位无进展生存期为 24.8 个月（95% 置信区间 [CI]，22.1 至不可估计），而安慰剂-来曲唑组的中位无进展生存期为 14.5 个月（95% CI，12.9 至 17.1）组（疾病进展或死亡的风险比，0.58；95% CI，0.46 至 0.72；P
BACKGROUNDA phase 2 study showed that progression-free survival was longer with palbociclib plus letrozole than with letrozole alone in the initial treatment of postmenopausal women with estrogen-receptor (ER)-positive, human epidermal growth factor receptor 2 (HER2)-negative advanced breast cancer. We performed a phase 3 study that was designed to confirm and expand the efficacy and safety data for palbociclib plus letrozole for this indication.METHODSIn this double-blind study, we randomly assigned, in a 2: 1 ratio, 666 postmenopausal women with ER-positive, HER2-negative breast cancer, who had not had prior treatment for advanced disease, to receive palbociclib plus letrozole or placebo plus letrozole. The primary end point was progression-free survival, as assessed by the investigators; secondary end points were overall survival, objective response, clinical benefit response, patient-reported outcomes, pharmacokinetic effects, and safety.RESULTSThe median progression-free survival was 24.8 months (95% confidence interval [CI], 22.1 to not estimable) in the palbociclib-letrozole group, as compared with 14.5 months (95% CI, 12.9 to 17.1) in the placebo-letrozole group (hazard ratio for disease progression or death, 0.58; 95% CI, 0.46 to 0.72; P