Institut Jules Bordet, l'Université Libre de Bruxelles, Brussels, Belgium.
Curr Opin Oncol. 2012 Nov;24(6):612-22. doi: 10.1097/CCO.0b013e328358a29a.
Many antihuman epidermal growth factor receptor (anti-HER2)-targeted agents, covering a broad spectrum of mechanisms of action, have been recently developed. The concept of dual anti-HER2 blockade has been preclinically and clinically assessed with positive results. In this article, the authors review the biologic rationale for dual HER2 blockade, along with the clinical findings.
Dual anti-HER2 blockade has been assessed in the metastatic setting, including with chemotherapy-free regimens, leading to impressive responses, even in heavily pretreated patients. In the neoadjuvant setting, dual anti-HER2 blockade combinations and chemotherapy have almost doubled the rates of pathologic complete response compared to single anti-HER2 therapy. Similar strategies are now actively being pursued in the adjuvant setting and, it is hoped, will improve the outcome of many patients with HER2-positive breast cancer.
Combining different anti-HER2-targeted agents represents a promising therapeutic strategy, now reaching clinical practice. There are major clinical challenges yet to be resolved, rising from the increasing number of potential combinations and their mechanisms of resistance. Smartly designed clinical trials are required to address these challenges and perhaps to define a subset of patients that can be spared chemotherapy.
近年来，已经开发出许多针对人表皮生长因子受体（抗 HER2）的靶向药物，涵盖了广泛的作用机制。双抗 HER2 阻断的概念已在临床前和临床中得到了积极评估。本文作者综述了双 HER2 阻断的生物学依据以及临床研究结果。
在转移性疾病环境中评估了双抗 HER2 阻断，包括无化疗方案，即使是在经过大量预处理的患者中，也取得了令人印象深刻的疗效。在新辅助治疗环境中，双抗 HER2 阻断联合化疗与单药抗 HER2 治疗相比，病理完全缓解率几乎翻了一番。目前，类似的策略正在辅助治疗环境中积极探索，并有望改善许多 HER2 阳性乳腺癌患者的预后。
联合使用不同的抗 HER2 靶向药物代表了一种很有前途的治疗策略，目前已经应用于临床实践。但仍存在一些重大的临床挑战需要解决，这源于越来越多的潜在联合治疗方案及其耐药机制。需要精心设计临床试验来应对这些挑战，并可能确定可以避免化疗的特定患者群体。
