帕妥珠单抗、曲妥珠单抗和多西他赛用于治疗既往未接受治疗的人表皮生长因子受体 2（HER2）阳性局部复发或转移性乳腺癌的中国患者（PUFFIN）：一项随机、双盲、安慰剂对照的 III 期研究的最终分析。
Pertuzumab, trastuzumab, and docetaxel for Chinese patients with previously untreated HER2-positive locally recurrent or metastatic breast cancer (PUFFIN): final analysis of a phase III, randomized, double-blind, placebo-controlled study.
机构信息
Department of Medical Oncology National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences, and Peking Union Medical College, Beijing, China.
The Cancer Center, The First Hospital of Jilin University, Changchun, Jilin, China.
出版信息
Breast Cancer Res Treat. 2023 Feb;197(3):503-513. doi: 10.1007/s10549-022-06775-1. Epub 2022 Dec 4.
PURPOSE
PUFFIN (NCT02896855), a Chinese bridging study in patients with previously untreated HER2-positive locally recurrent or metastatic breast cancer, assessed consistency of efficacy and safety of pertuzumab plus trastuzumab and docetaxel versus placebo, trastuzumab, and docetaxel, with CLEOPATRA (NCT00567190).
METHODS
Eligible patients, n = 243, were randomized 1:1, stratified by visceral disease and hormone receptor status, to pertuzumab, trastuzumab, and docetaxel or placebo, trastuzumab, and docetaxel.
PRIMARY ENDPOINT
investigator-assessed progression-free survival (PFS). Secondary endpoints: safety and overall survival (OS). After primary analysis, patients could cross over to the pertuzumab arm.
RESULTS
Updated median PFS: 16.5 months (pertuzumab arm) and 12.5 months (placebo arm), with a hazard ratio (HR) of 0.60 [95% confidence interval (CI) 0.45, 0.81; p = 0.0008]. Median OS was not reached in either arm; the OS HR was 0.68 (95% CI 0.45, 1.03; p = 0.0658). Safety was similar in both arms with no new safety signals: 73.8% (pertuzumab arm) and 69.2% (placebo arm) experienced grade ≥ 3 adverse events. No heart failure, symptomatic left ventricular systolic dysfunction, or left ventricular ejection fraction decline of < 40% were reported.
CONCLUSIONS
The PUFFIN final analysis showed, per the primary analysis, that overall efficacy of pertuzumab plus trastuzumab and docetaxel was consistent with CLEOPATRA. Safety remained consistent with the known pertuzumab profile. Overall, PUFFIN contributes to the totality of data with pertuzumab in previously untreated HER2-positive locally recurrent or metastatic breast cancer and supports the favorable benefit-risk profile of pertuzumab in Chinese patients.
TRIAL REGISTRATION
ClinicalTrials.gov, NCT02896855, registered 7 September 2016.
目的
PUFFIN（NCT02896855）是一项针对既往未经治疗的 HER2 阳性局部复发或转移性乳腺癌患者的中文桥接研究，评估了培妥珠单抗联合曲妥珠单抗和多西他赛与安慰剂、曲妥珠单抗和多西他赛在 CLEOPATRA（NCT00567190）中的疗效和安全性的一致性。
方法
符合条件的 243 例患者按 1:1 比例随机分组，按内脏疾病和激素受体状态分层，分别接受培妥珠单抗、曲妥珠单抗和多西他赛或安慰剂、曲妥珠单抗和多西他赛治疗。
主要终点
研究者评估的无进展生存期（PFS）。次要终点：安全性和总生存期（OS）。首次分析后，患者可以交叉到培妥珠单抗组。
结果
更新后的中位 PFS：16.5 个月（培妥珠单抗组）和 12.5 个月（安慰剂组），风险比（HR）为 0.60（95%置信区间 0.45，0.81；p=0.0008）。两组均未达到中位 OS；OS HR 为 0.68（95%CI 0.45，1.03；p=0.0658）。两组安全性相似，无新的安全性信号：73.8%（培妥珠单抗组）和 69.2%（安慰剂组）发生了≥3 级不良事件。未报告心力衰竭、有症状的左室收缩功能障碍或左室射血分数下降<40%。
结论
PUFFIN 的最终分析显示，与首次分析一致，培妥珠单抗联合曲妥珠单抗和多西他赛的总体疗效与 CLEOPATRA 一致。安全性与已知的培妥珠单抗特征一致。总体而言，PUFFIN 为先前未经治疗的 HER2 阳性局部复发或转移性乳腺癌中使用培妥珠单抗提供了更多的数据支持，并支持在中国患者中使用培妥珠单抗具有良好的获益风险比。
试验注册
ClinicalTrials.gov，NCT02896855，于 2016 年 9 月 7 日注册。
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