Division of Early Drug Development for Innovative Therapy, IEO, European Institute of Oncology IRCCS , Milan , Italy.
Department of Oncology and Haematology, University of Milan , Milan , Italy.
Expert Rev Anticancer Ther. 2019 Sep;19(9):811-822. doi: 10.1080/14737140.2019.1660164. Epub 2019 Aug 28.
: Despite dramatic improvements in survival achieved with currently available anti-HER2 agents, HER2-positive metastatic breast cancer remains an almost invariably deadly disease, with primary or acquired resistance to HER2-directed agents developing during treatment. Many efforts are focused on identifying new agents that may more effectively inhibit HER2 signaling and on possible combination strategies. : This review summarizes the landscape of drugs under development for HER2-positive metastatic breast cancer, as antibody-drug conjugates, monoclonal anti-HER2 antibodies, bispecific antibodies, or novel tyrosine kinase inhibitors. Moreover, available data for possible combination of anti-HER2 drugs and different agents, as immunotherapy, PI3K/mTOR inhibitors, CDK4/6 inhibitors currently under evaluation are reviewed. These strategies may overcome mechanisms of resistance and further improve patient outcomes. : Identification of valuable predictive biomarkers is needed to better inform choice of treatment sequence for the individual patient and limit the financial toxicity of these agents.
尽管目前可用的抗 HER2 药物显著提高了生存率，但 HER2 阳性转移性乳腺癌仍然是一种几乎无法治愈的疾病，在治疗过程中会出现对 HER2 靶向药物的原发性或获得性耐药。许多研究都集中在寻找可能更有效地抑制 HER2 信号的新药物以及可能的联合策略上。
这篇综述总结了正在开发的用于治疗 HER2 阳性转移性乳腺癌的药物，包括抗体药物偶联物、单克隆抗 HER2 抗体、双特异性抗体或新型酪氨酸激酶抑制剂。此外，还回顾了抗 HER2 药物与不同药物联合使用的可能，如免疫疗法、PI3K/mTOR 抑制剂、CDK4/6 抑制剂正在评估中。这些策略可能克服耐药机制，进一步改善患者的预后。
需要确定有价值的预测生物标志物，以便更好地为个体患者选择治疗方案，并限制这些药物的财务毒性。
