Palbociclib for Hormone-Receptor-Positive, HER2-Positive Advanced Breast Cancer.

On the basis of preclinical and clinical data, the addition of palbociclib (a selective inhibitor of cyclin-dependent kinases 4 and 6) may overcome resistance to both endocrine and HER2-directed therapies.

基于临床前和临床数据，添加帕博西利布（一种选择性抑制细胞周期依赖性激酶4和6的药物）可能克服对内分泌和HER2靶向治疗的耐药性。

Methods

In this phase 3, open-label, randomized trial, we enrolled patients with hormone-receptor-positive, HER2-positive metastatic breast cancer who did not have disease progression after four to eight cycles of chemotherapy plus HER2-targeted therapy.

在这项III期、开放标签、随机试验中，我们招募了接受4至8个周期化疗加HER2靶向治疗后疾病未进展的激素受体阳性、HER2阳性转移性乳腺癌患者。

Patients were randomly assigned in a 1:1 ratio to receive maintenance HER2-targeted and endocrine therapies with or without palbociclib.

患者按1:1的比例随机分配接受维持HER2靶向治疗和内分泌治疗，有或没有帕博西利。

The primary end point was investigator-assessed progression-free survival. Secondary end points included the objective response, clinical benefit, safety, and overall survival.

主要终点是研究者评估的无进展生存期。次要终点包括客观反应、临床获益、安全性和总生存期。

Results

A total of 518 patients underwent randomization: 261 were assigned to receive palbociclib and 257 to receive standard therapy.

共有518名患者进行了随机分组：261名被分配接受帕博西利治疗，257名接受标准治疗。

At a median follow-up of 53.5 months, patients in the palbociclib group had significantly longer progression-free survivalthan those in the standard-therapy group (median duration, 44.3 months vs. 29.1 months; hazard ratiofor disease progression or death, 0.75; 95% confidence interval, 0.59 to 0.96; two-sided P = 0.02).

在中位随访53.5个月时，与标准治疗组相比，帕博西利组患者的无进展生存期显著更长（中位持续时间，44.3个月对比29.1个月；疾病进展或死亡的风险比为0.75；95%置信区间为0.59至0.96；双侧P值=0.02）。

Grade 3 and 4 adverse events, predominantly from neutropenia, occurred in 79.7% and 10.0% of the patients, respectively, in the palbociclib group, as compared with 30.6% and 3.6% of the patients, respectively, in the standard-therapy group.

在帕博西利组中，分别有79.7%和10.0%的患者出现了3级和4级不良事件，主要为中性粒细胞减少症，而在标准治疗组中，分别有30.6%和3.6%的患者出现了3级和4级不良事件。

Conclusions

The addition of palbociclib to maintenance anti-HER2 and endocrine therapies led to a significant improvement in progression-free survivalover standard therapy, with increased toxic effects, mainly neutropenia.

将帕博西利添加到维持抗HER2和内分泌治疗中，与标准治疗相比，显著改善了无进展生存期，但毒性效应增加，主要是中性粒细胞减少症。

(Funded by Pfizer and others; PATINA ClinicalTrials.gov number, NCT02947685.).

(由辉瑞等公司资助；PATINA临床试验注册号，NCT02947685。)