Rubovszky Gábor, Láng István
B Belgyógyászati-Onkológiai és Klinikai Farmakológiai Osztály, Országos Onkológiai Intézet, Budapest, Hungary.
Magy Onkol. 2014 Jun;58(2):128-32. Epub 2014 Feb 20.
The expansion of molecular genetic knowledge leads to targeted therapy which is a common part of cancer treatment. Targeted agents also exist for breast cancer. However, new efficient molecules are urgently needed. On one hand, there are cancer subgroups where we do not have efficient targeted drugs, on the other hand, the results of established cancer therapies can be improved by interfering with another signal transduction pathway. Everolimus is a targeted agent which was effective in several clinical trials and became registered for treatment of hormone receptor positive breast cancer. This article summarizes the results of published breast cancer everolimus trials. The results of two phase 3 trials are available. In the BOLERO-2 trial exemestane was compared with the combination of exemestane and everolimus, while in BOLERO-3 trial trastuzumab and vinorelbine were investigated with or without everolimus. In both trials the progression-free survival was significantly longer in the experimental arm. The overall survival data of BOLERO-2 trial, a secondary end point, are also available. The 4.4 month benefit in the experimental arm is clinically important but it has not reached the level of statistical significance. We have not had biomarkers so far that could help us to identify a subgroup of cancers sensitive to everolimus.
分子遗传学知识的扩展催生了靶向治疗，这已成为癌症治疗的常见手段。针对乳腺癌的靶向药物也已存在。然而，目前迫切需要新型高效分子。一方面，存在一些癌症亚组，我们尚未拥有有效的靶向药物；另一方面，通过干扰另一条信号转导通路，现有癌症治疗的效果有望得到改善。依维莫司是一种靶向药物，在多项临床试验中显示出疗效，并已获批用于治疗激素受体阳性乳腺癌。本文总结了已发表的依维莫司治疗乳腺癌试验的结果。两项3期试验的结果可供参考。在BOLERO - 2试验中，将依西美坦与依西美坦联合依维莫司进行了对比；而在BOLERO - 3试验中，研究了曲妥珠单抗和长春瑞滨联合或不联合依维莫司的情况。在这两项试验中，试验组的无进展生存期均显著延长。BOLERO - 2试验的总生存数据作为次要终点也已公布。试验组4.4个月的获益具有临床意义，但尚未达到统计学显著水平。到目前为止，我们还没有能够帮助我们识别对依维莫司敏感的癌症亚组的生物标志物。
