帕博西尼联合来曲唑治疗晚期乳腺癌。

Palbociclib and Letrozole in Advanced Breast Cancer.

机构信息

From the Department of Medicine, Division of Hematology and Oncology, David Geffen School of Medicine at the University of California, Los Angeles, Santa Monica (R.S.F., D.J.S.), the Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco (H.S.R.), and Pfizer, La Jolla (E.G., D.R.L., S.R.) - all in California; Hospital Gregorio Maranon, Universidad Complutense, Madrid (M.M.); U.S. Oncology Research, The Woodlands, TX (S.J.); Cancer Research Institute, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, South Korea (S.-A.I.); British Columbia Cancer Agency, Vancouver, Canada (K.G.); Brustzentrum der Universität München (LMU), Munich, Germany (N.H.); State Budget Medical Institution Republican Clinical Oncology, Ufa, Russia (O.N.L.); All-Ireland Cooperative Oncology Research Group, Dublin (J.M.W.); M.D. Anderson Cancer Center, University of Texas, Houston (S.M.); and Institut Curie, Paris (V.D.).

出版信息

N Engl J Med. 2016 Nov 17;375(20):1925-1936. doi: 10.1056/NEJMoa1607303.

DOI:10.1056/NEJMoa1607303

PMID:27959613

Abstract

BACKGROUND

A 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.

METHODS

In 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.

RESULTS

The 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<0.001). The most common grade 3 or 4 adverse events were neutropenia (occurring in 66.4% of the patients in the palbociclib-letrozole group vs. 1.4% in the placebo-letrozole group), leukopenia (24.8% vs. 0%), anemia (5.4% vs. 1.8%), and fatigue (1.8% vs. 0.5%). Febrile neutropenia was reported in 1.8% of patients in the palbociclib-letrozole group and in none of the patients in the placebo-letrozole group. Permanent discontinuation of any study treatment as a result of adverse events occurred in 43 patients (9.7%) in the palbociclib-letrozole group and in 13 patients (5.9%) in the placebo-letrozole group.

CONCLUSIONS

Among patients with previously untreated ER-positive, HER2-negative advanced breast cancer, palbociclib combined with letrozole resulted in significantly longer progression-free survival than that with letrozole alone, although the rates of myelotoxic effects were higher with palbociclib-letrozole. (Funded by Pfizer; PALOMA-2 ClinicalTrials.gov number, NCT01740427 .).

摘要

背景

一项 2 期研究显示，在初始治疗绝经后雌激素受体（ER）阳性、人表皮生长因子受体 2（HER2）阴性的晚期乳腺癌患者中，与单独使用来曲唑相比，帕博西尼联合来曲唑可使无进展生存期更长。我们进行了一项 3 期研究，旨在确认和扩展帕博西尼联合来曲唑在这一适应证中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 名未接受过晚期疾病治疗的绝经后 ER 阳性、HER2 阴性乳腺癌患者，接受帕博西尼联合来曲唑或安慰剂联合来曲唑治疗。主要终点是无进展生存期，由研究者评估；次要终点是总生存期、客观缓解、临床获益反应、患者报告的结局、药代动力学效应和安全性。

结果

在帕博西尼-来曲唑组中，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-来曲唑组为 14.5 个月（95%CI，12.9 至 17.1）（疾病进展或死亡的风险比，0.58；95%CI，0.46 至 0.72；P<0.001）。最常见的 3 级或 4 级不良事件是中性粒细胞减少症（发生在帕博西尼-来曲唑组的 66.4%的患者中，而安慰剂-来曲唑组为 1.4%）、白细胞减少症（24.8%对 0%）、贫血（5.4%对 1.8%）和疲劳（1.8%对 0.5%）。发热性中性粒细胞减少症在帕博西尼-来曲唑组的 1.8%的患者中发生，而在安慰剂-来曲唑组中无患者发生。由于不良事件而永久停止任何研究治疗的患者在帕博西尼-来曲唑组为 43 例（9.7%），在安慰剂-来曲唑组为 13 例（5.9%）。