National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences, and Peking Union Medical College, Beijing, China.
The Cancer Center, The First Hospital of Jilin University, Jilin, China.
Breast Cancer Res Treat. 2020 Aug;182(3):689-697. doi: 10.1007/s10549-020-05728-w. Epub 2020 Jun 20.
The Chinese bridging study PUFFIN (NCT02896855) aimed to assess consistency of efficacy with CLEOPATRA (NCT00567190), investigating pertuzumab with trastuzumab and docetaxel versus placebo, trastuzumab, and docetaxel in patients with previously untreated HER2-positive locally recurrent or metastatic breast cancer.
Patients were randomized 1:1, stratified by visceral/non-visceral disease and hormone receptor status. The primary endpoint was investigator-assessed progression-free survival (PFS). Secondary endpoints included objective response rate (in patients with measurable baseline disease), overall survival, and safety. The consistency threshold for PFS (hazard ratio [HR] < 0.81) (maintaining ≥ 50% of the risk reduction determined in CLEOPATRA [HR 0.62]) determined the target sample size (n = 240).
Two hundred forty-three patients were randomized. Median PFS was 14.5 months in the pertuzumab arm (95% confidence interval [CI] 12.5, 18.6) and 12.4 months in the placebo arm (95% CI 10.4, 12.7) in the intention-to-treat population (HR: 0.69 [95% CI 0.49, 0.99]). Objective responses were recorded in 83/105 (79.0%) and 67/97 (69.1%) patients, respectively. Grade ≥ 3 adverse events (70.5% and 69.2%, respectively) and serious adverse events (19.7% and 19.2%, respectively) were similar across both arms. No heart failure cases or symptomatic left ventricular ejection fraction declines were reported.
PUFFIN met its primary objective. Overall, efficacy data were consistent with CLEOPATRA. Safety was consistent with the known pertuzumab safety profile. PUFFIN adds 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.
中国桥接研究 PUFFIN（NCT02896855）旨在评估与 CLEOPATRA（NCT00567190）的疗效一致性，评估曲妥珠单抗联合培妥珠单抗和多西他赛与安慰剂、曲妥珠单抗和多西他赛在未经治疗的局部复发或转移性 HER2 阳性乳腺癌患者中的疗效。
患者按 1:1 随机分组，按内脏/非内脏疾病和激素受体状态分层。主要终点为研究者评估的无进展生存期（PFS）。次要终点包括客观缓解率（基线有可测量疾病的患者）、总生存期和安全性。PFS 的一致性阈值（风险比 [HR] < 0.81）（保持 CLEOPATRA 中确定的风险降低≥50%[HR 0.62]）确定了目标样本量（n = 240）。
243 例患者被随机分组。意向治疗人群中，培妥珠单抗组中位 PFS 为 14.5 个月（95%置信区间 [CI] 12.5，18.6），安慰剂组为 12.4 个月（95%CI 10.4，12.7）（HR：0.69 [95%CI 0.49，0.99]）。分别有 83/105（79.0%）和 67/97（69.1%）例患者记录了客观缓解。培妥珠单抗组和安慰剂组分别有 70.5%和 69.2%的患者发生了≥3 级不良事件（分别为 70.5%和 69.2%），19.7%和 19.2%的患者发生了严重不良事件（分别为 19.7%和 19.2%）。两组均未报告心力衰竭病例或有症状的左心室射血分数下降。
PUFFIN 达到了主要目标。总体而言，疗效数据与 CLEOPATRA 一致。安全性与已知的培妥珠单抗安全性特征一致。PUFFIN 在未经治疗的局部复发或转移性 HER2 阳性乳腺癌中增加了培妥珠单抗的数据总和，并支持在中国患者中培妥珠单抗的有利获益风险特征。
ClinicalTrials.gov，NCT02896855，于 2016 年 9 月 7 日注册。
