在2016年圣安东尼奥乳腺癌研讨会上,我们介绍了几项有趣的II期和III期研究,这些研究调查了转移性乳腺癌的全身治疗.PrEGOC0102试验表明,氟维司群联合依维莫司是安全有效的,可替代依西美坦联合依维莫司治疗激素受体阳性患者,HER2阴性疾病。在BELLE-3试验中,依维莫司失败后,pan-PI3K抑制剂布帕利布与氟维司群联合使用显示出一定的活性。在循环肿瘤DNA(ctDNA)中检测到的PIK3CA突变可预测布帕利西的疗效。不幸的是,不利的毒性特征阻碍了该药物的进一步开发。尽管如此,PI3K似乎是对mTOR抑制具有抗性的肿瘤的有效靶标。在BRCA1/2种系突变患者中,通过在卡铂和紫杉醇中添加PARP抑制剂veliparib,BROCADEII期试验未能显示出统计学上的显着益处。总体反应率,然而,与安慰剂组相比,veliparib组具有统计学意义。来自III期试验BROCADE-3的数据正在等待中。最后,TNT试验没有确定进一步的生物标志物,除了BRCA1/2种系突变,卡铂在转移性三阴性乳腺癌患者中的获益。
At the 2016 San Antonio Breast Cancer Symposium, several interesting phase II and phase III studies investigating systemic therapies for metastatic breast cancer were presented. The PrEGOC 0102 trial demonstrated that the combination of fulvestrant plus everolimus is safe and effective and could be an alternative to exemestane plus everolimus for selected patients with hormone-receptor positive, HER2-negative disease. The pan-PI3K inhibitor buparlisib showed some activity in combination with fulvestrant after failure of everolimus in the BELLE-3 trial. PIK3CA mutation detected in circulating tumor DNA (ctDNA) was predictive for a buparlisib efficacy. Unfortunately, the unfavorable toxicity profile precludes further development of this drug. Nonetheless, PI3K seems to be a valid target in tumors resistant to mTOR inhibition. The BROCADE phase II trial failed to show a statistically significant benefit by the addition of the PARP inhibitor veliparib to carboplatin and paclitaxel in patients with BRCA1/2 germline mutation. The overall response rate, however, was statistically significant higher in the veliparib arm compared to the placebo arm. Data from the phase III trial BROCADE-3 are awaited. Finally, the TNT trial did not identify further biomarkers, in addition to BRCA1/2 germline mutation, for carboplatin benefit in patients with metastatic triple-negative breast cancer.