曲妥珠单抗-帕妥珠单抗联合艾瑞布林或紫杉烷作为人表皮生长因子2阳性局部晚期/转移性乳腺癌的一线化疗：随机非劣效性III期EMERALD试验
Trastuzumab-Pertuzumab Plus Eribulin or Taxane as First-Line Chemotherapy for Human Epidermal Growth Factor 2-Positive Locally Advanced/Metastatic Breast Cancer: The Randomized Noninferiority Phase III EMERALD Trial.
作者信息
Yamashita Toshinari, Saji Shigehira, Takano Toshimi, Naito Yoichi, Tsuneizumi Michiko, Yoshimura Akiyo, Takahashi Masato, Tsurutani Junji, Iwatani Tsuguo, Kitada Masahiro, Tada Hiroshi, Mori Natsuko, Higuchi Toru, Iwasa Tsutomu, Araki Kazuhiro, Koizumi Kei, Hasegawa Hiroki, Uchida Yohei, Morita Satoshi, Masuda Norikazu
机构信息
Department of Breast Surgery and Oncology, Kanagawa Cancer Center, Kanagawa, Japan.
Department of Medical Oncology, Fukushima Medical University, Fukushima, Japan.
出版信息
J Clin Oncol. 2025 Apr 10;43(11):1302-1313. doi: 10.1200/JCO-24-01888. Epub 2025 Jan 9.
PURPOSE
Trastuzumab-pertuzumab (HP) plus taxane is a current standard first-line therapy for recurrent or metastatic human epidermal growth factor 2 (HER2)+ breast cancer (BC). We investigated noninferiority of eribulin to a taxane when combined with dual HER2 blockade as first-line systemic treatment for locally advanced/metastatic HER2+ BC.
METHODS
In the phase III EMERALD trial (target sample size, 480; ClinicalTrials.gov identifier: NCT03264547/UMIN000027938), patients were randomly assigned (1:1) to receive eribulin 1.4 mg/m once daily on days 1 and 8 (eribulin group) or a taxane (docetaxel 75 mg/m once on day 1 or paclitaxel 80 mg/m once daily on days 1, 8, and 15; taxane group) intravenously in a 21-day cycle, each with HP on day 1. The primary end point was progression-free survival (PFS; intention-to-treat population). Secondary end points included objective response rate, overall survival (OS), patient-reported quality of life (QoL), and safety. Noninferiority was tested using the stratified Cox proportional hazards model to estimate hazard ratios (HRs) for PFS events, with a noninferiority HR margin of 1.33.
RESULTS
Between August 2017 and June 2021, 446 patients (median age, 56.0 years) were enrolled. The median PFS was 14.0 and 12.9 months in the eribulin group (n = 224) and taxane group (n = 222 [docetaxel/paclitaxel, n = 186/36]), respectively (HR, 0.95 [95% CI, 0.76 to 1.19]), which confirmed the noninferiority of the study regimen. The median OS was 65.3 months in the taxane group but has not been reached in the eribulin group. Median time to QoL deterioration was numerically longer with eribulin than with taxane. Adverse event (AE) rates were similar, despite the longer duration of eribulin use. Infusion reaction, skin-related AEs, diarrhea, and edema were more common with taxane, whereas neutropenia was more common with eribulin.
CONCLUSION
The results suggested that eribulin + HP is an option for first-line treatment of locally advanced/metastatic HER2+ BC.
目的
曲妥珠单抗-帕妥珠单抗（HP）联合紫杉烷是复发或转移性人表皮生长因子2（HER2）阳性乳腺癌（BC）当前的标准一线治疗方案。我们研究了在联合双重HER2阻断作为局部晚期/转移性HER2阳性BC的一线全身治疗时，艾日布林相对于紫杉烷的非劣效性。
方法
在III期EMERALD试验（目标样本量480；ClinicalTrials.gov标识符：NCT03264547/UMIN000027938）中，患者被随机分配（1:1）接受艾日布林1.4mg/m²，在第1天和第8天每日一次（艾日布林组），或一种紫杉烷（多西他赛75mg/m²在第1天单次给药，或紫杉醇80mg/m²在第1天、第8天和第15天每日一次；紫杉烷组），静脉滴注，每21天为一个周期，两组均在第1天给予HP。主要终点为无进展生存期（PFS；意向性治疗人群）。次要终点包括客观缓解率、总生存期（OS）、患者报告的生活质量（QoL）和安全性。使用分层Cox比例风险模型测试非劣效性，以估计PFS事件的风险比（HR），非劣效性HR界值为1.33。
结果
2017年8月至2021年6月期间，共纳入446例患者（中位年龄56.0岁）。艾日布林组（n = 224）和紫杉烷组（n = 222 [多西他赛/紫杉醇，n = 186/36]）的中位PFS分别为14.0个月和12.9个月（HR，0.95 [95%CI，0.76至1.19]），这证实了研究方案的非劣效性。紫杉烷组的中位OS为65.3个月，但艾日布林组尚未达到。从数值上看，艾日布林组QoL恶化的中位时间比紫杉烷组长。尽管艾日布林的使用时间更长，但不良事件（AE）发生率相似。输注反应、皮肤相关AE、腹泻和水肿在紫杉烷组更常见，而中性粒细胞减少在艾日布林组更常见。
结论
结果表明，艾日布林 + HP是局部晚期/转移性HER2阳性BC一线治疗的一种选择。
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