O'Reilly David, Sendi Maha Al, Kelly Catherine M
Department of Medical Oncology, Mater Misericordiae University Hospital, Dublin 1, Ireland.
World J Clin Oncol. 2021 Mar 24;12(3):164-182. doi: 10.5306/wjco.v12.i3.164.
Metastatic triple negative breast cancer (TNBC) has an aggressive phenotype with a predilection for visceral organs and brain. Best responses to chemotherapy are predominately in the first line. Recent studies have demonstrated improved progression free survival with the combination of atezolizumab/pembrolizumab and chemotherapy in programmed death-ligand 1 positive metastatic TNBC. However, a recent trial in a similar population showed no benefit for atezoli-zumab and paclitaxel which led to a Food and Drug Administration alert. Two phase III trials (OLYMPIAD and BROCADE3) demonstrated a benefit in progression free survival (PFS) but not overall survival in patients with BRCA-associated metastatic TNBC treated with Olaparib or Talazoparib respectively. For those treated with Talazoparib, the time to deterioration in health related-quality of life was also longer compared to chemotherapy. The BROCADE3 trial demonstrated that the combination of a platinum and veliparib increased PFS in first-line metastatic TNBC but at the cost of increased toxicity. There are no head-to-head comparisons of a poly (adenosine diphosphate-ribose) polymerase inhibitors (PARPi) and platinums. There are unanswered questions regarding the role of PARPi maintenance after platinum therapy as is standard of care in BRCA-associated ovarian cancer. Other areas of therapeutic interest include targeting aberrations in the phosphoinositide 3-kinase pathway, protein kinase B, mammalian target of rapamycin or utilising antibody drug conjugates. This review focusses on recent and emerging therapeutic options in metastatic TNBC. We searched PubMed, clinicaltrials.gov and recent international meetings from American Society of Clinical Oncology, San Antonio Breast Cancer Conference and the European Society of Medical Oncology.
转移性三阴性乳腺癌（TNBC）具有侵袭性表型，易转移至内脏器官和脑。化疗的最佳反应主要出现在一线治疗中。最近的研究表明，在程序性死亡配体1阳性的转移性TNBC中，阿特珠单抗/帕博利珠单抗与化疗联合使用可改善无进展生存期。然而，最近在类似人群中进行的一项试验显示，阿特珠单抗与紫杉醇联合使用并无益处，这导致了美国食品药品监督管理局发出警报。两项III期试验（OLYMPIAD和BROCADE3）分别显示，奥拉帕利或他拉唑帕利治疗BRCA相关转移性TNBC患者可使无进展生存期（PFS）获益，但总生存期未获益。对于接受他拉唑帕利治疗的患者，与化疗相比，健康相关生活质量恶化的时间也更长。BROCADE3试验表明，铂类与维利帕利联合使用可提高一线转移性TNBC的PFS，但代价是毒性增加。聚（腺苷二磷酸-核糖）聚合酶抑制剂（PARPi）与铂类之间尚无直接对比研究。关于PARPi在铂类治疗后维持治疗的作用，如同BRCA相关卵巢癌的标准治疗一样，仍存在未解决的问题。其他治疗关注领域包括靶向磷酸肌醇3激酶通路、蛋白激酶B、雷帕霉素哺乳动物靶点的异常，或使用抗体药物偶联物。本综述聚焦于转移性TNBC近期和新出现的治疗选择。我们检索了PubMed、clinicaltrials.gov以及美国临床肿瘤学会、圣安东尼奥乳腺癌会议和欧洲医学肿瘤学会近期国际会议的资料。
