医脉通编译，转载请注明出处
2016年6月3-7日，一年一度的美国临床肿瘤学会（American Society of Clinical Oncology，ASCO）年会在芝加哥举办。6月6日下午的乳腺癌——ER/HER2 口头报告专场上，一项摘要号为 LBA503 的随机 Ⅲ 期试验 Heritage 研究将进行口头报告。该研究比较了曲妥珠单抗及其生物类似药 MYL-1401O 在一线治疗晚期 HER2 阳性乳腺癌患者方面的有效性和安全性。医脉通报道：
据一项随机 Ⅲ 期研究显示，在晚期 HER2 阳性乳腺癌患者的一线治疗方面，曲妥珠单抗的生物类似药 MYL-1401O 在有效性和安全性方面与曲妥珠单抗相似。研究中的曲妥珠单抗组和 MYL-1401O 组患者获得了相似的缓解率，同时安全性方面两组也无显著性差异。
“曲妥珠单抗显著的改善了 HER2 阳性乳腺癌患者的生存，但是由于其较高的费用，世界上仍有很多患者无法使用曲妥珠单抗”，研究的第一作者，加州大学医学部教授 Hope S. Rugo 博士介绍道，“我们希望这种生物类似药将能改善有效药物的可及性，这种药物已使全球上万人获益。”
来自亚洲、拉丁美洲、非洲和欧洲的95个机构参与了这项随机 Ⅲ 期研究，共入组了500位转移性 HER2 阳性乳腺癌患者。患者随机接受紫杉类化疗联用曲妥珠单抗或联用 MYL-1401O 方案作为一线治疗方案。
患者至少接受八个周期的化疗联用曲妥珠单抗/MYL-1401O 治疗。该方案与临床试验和临床实践中曲妥珠单抗治疗转移性乳腺癌的方案是一致的。研究人员在患者接受治疗后24周时评估两组的缓解率。
研究结果
该研究显示 MYL-1401O 在疗效和安全性方面与曲妥珠单抗是等效的，同时该药不会引起免疫反应（低免疫原性）。
500位患者中，共有458位患者进行了有效性评估，24周时 MYL-1401O 组的总缓解率 ORR 为69.6%，曲妥珠单抗组的 ORR 为64%，差异符合等效标准。患者的 PFS 数据尚不成熟。
两组的免疫原性和安全性相似。严重不良事件（AE）方面，MYL-1401O 组发生率为38%，曲妥珠单抗组发生率为36%。最常见严重 AE 为低血细胞计数（嗜中性粒细胞减少症），两组在心功能方面的数据无显著性差异。两组均有4例治疗相关死亡。
“据我们所知，该研究是第一项显示生物类似药与曲妥珠单抗具有等效性的研究”，Rugo 博士介绍道。
研究人员之前的已显示了在生物学特征和物理化学特征方面 MYL-1401O 与曲妥珠单抗具有相似性。有效性和安全性方面的分析是药品监管部门对生物类似药的要求的一部分。
会议专题》》》2016年ASCO年会专题报道
摘要原文：
Heritage: A phase III safety and efficacy trial of the proposed trastuzumab biosimilar Myl-1401O versus Herceptin.（Abstract LBA503）
Authors：Hope S. Rugo, Abhijit Barve, et al.
Session Type：Oral Abstract Session: Breast Cancer—HER2/ER
Background: Trastuzumab has revolutionized treatment of HER2+ breast cancer. Globally accessible alternatives are a critical need. We evaluated Myl-1401O, a proposed trastuzumab biosimilar, as treatment for HER2+ metastatic breast cancer (MBC), based on physicochemical analyses, nonclinical, pharmacokinetic and pharmacodynamic studies.
Methods: Heritage is a double-blind, randomized clinical trial designed to evaluate comparative efficacy and safety of Myl-1401O vs Herceptin. Eligible patients (pts) had centrally confirmed, measurable HER2+ MBC without prior chemotherapy or trastuzumab for metastatic disease. Pts were randomized to receive either Myl-1401O or Herceptin with docetaxel or paclitaxel for a minimum of 8 cycles. Trastuzumab was continued until progression. The primary endpoint was overall response (ORR) at Week 24 by blinded central evaluation using RECIST 1.1. Secondary endpoints include progression free survival (PFS), overall survival, and safety. A sample size of 456 pts was calculated to demonstrate equivalence in ORR at Week 24 for MYL-1401O vs Herceptin, defined as a 90% confidence interval (CI) for the ratio of best ORR within the equivalence margin (0.81, 1.24).
Results: 500 pts were randomized, 458 were evaluable for efficacy. 44% had hormone receptor positive MBC, 84% received docetaxel. Week 24 ORR was 69.6% for Myl-14010 compared to 64% for Herceptin. The ratio of ORR was 1.09; both 90% CI (0.974-1.211) and 95% CI (0.954-1.237) were within the pre-defined equivalence margin. Median PFS is not yet reached (41 events for MYL-1401O vs 48 events for Herceptin). Safety was comparable; serious adverse events (primarily neutropenia related) occurred in 38% (MYL-1401O) vs 36% (Herceptin), with 4 fatal events in each arm. There was no significant change in cardiac function from baseline to Week 24 in either arm.
Conclusions: MYL-1401O was equivalent to Herceptin, given in combination with a taxane as first-line therapy for MBC, as measured by 24 week ORR. Safety was comparable. The proposed trastuzumab biosimilar MYL-1401O could be a new treatment option for HER2+ MBC.
