Okano Maiko, Ohtake Tohru, Saji Shigehira
Dept. of Organ Regulatory Surgery, Fukushima Medical University, School of Medicine.
Gan To Kagaku Ryoho. 2016 Apr;43(4):398-403.
In breast cancer treatment, molecular-targeted drugs such as trastuzumab and lapatinib have been used for many y ears, and the benefits have been seen in many patients. The molecular-targeted drugs have mainly been used in combination with cytotoxic agents; however, combination therapies with 2 molecular-targeted drugs are currently being investigated. The combination therapy of 2 HER2 receptor antibodies, pertuzumab and trastuzumab, has tremendous benefit for HER2 positive metastatic breast cancer patients. However, the combination of trastuzumab with tyrosine-kinase inhibitor lapatinib showed small benefits and its usage is limited. The combination of T-DM1 plus pertuzumab was not anymore effective than T-DM1 alone. The potentials of combined hormone therapies have been examined for ages. The combination of fulvestrant and aromatase inhibitor(AI)was shown to be beneficial in one phase III study; however, a conflicting result was reported by another large trial. To overcome hormone therapy resistance, the combinations of hormone therapy drugs with mTOR inhibitors(everolimus), pan-PI3K inhibitor(buparlisib), and CDK4/6 inhibitors(palbociclib, ribociclib, abemaciclib)are being investigated in various settings.
在乳腺癌治疗中，曲妥珠单抗和拉帕替尼等分子靶向药物已使用多年，许多患者从中受益。分子靶向药物主要与细胞毒性药物联合使用；然而，目前正在研究两种分子靶向药物的联合治疗。两种HER2受体抗体帕妥珠单抗和曲妥珠单抗的联合治疗对HER2阳性转移性乳腺癌患者有巨大益处。然而，曲妥珠单抗与酪氨酸激酶抑制剂拉帕替尼的联合治疗益处不大，其应用有限。T-DM1加帕妥珠单抗的联合治疗并不比单独使用T-DM1更有效。联合激素疗法的潜力已被研究多年。在一项III期研究中，氟维司群和芳香化酶抑制剂（AI）的联合治疗显示出益处；然而，另一项大型试验报告了相互矛盾的结果。为克服激素治疗耐药性，正在各种情况下研究激素治疗药物与mTOR抑制剂（依维莫司）、泛PI3K抑制剂（布帕利西布）和CDK4/6抑制剂（哌柏西利、瑞博西尼、阿贝西利）的联合应用。
