BACKGROUND Metastatic triple-negative breast cancer (mTNBC), an aggressive histological subtype, has poor prognosis. Chemotherapy remains standard of care for mTNBC, although no agent has been specifically approved for this breast cancer subtype. Instead, chemotherapies approved for metastatic breast cancer (MBC) are used for mTNBC (National Comprehensive Cancer Network Guidelines [NCCN] v1.2019). Atezolizumab in combination with nab-paclitaxel was recently approved for programmed death-ligand 1 (PD-L1)-positive locally advanced or metastatic TNBC. Published historical data were reviewed to characterize the efficacy of NCCN-recommended (v1.2016) agents as first-line (1L) and second-line or later (2L+) treatment for patients with locally recurrent inoperable or metastatic TNBC (collectively termed mTNBC herein). METHODS A systematic literature review was performed, examining clinical efficacy of therapies for mTNBC based on NCCN v1.2016 guideline recommendations. Data from 13 studies, either published retrospective mTNBC subgroup analyses based on phase III trials in MBC or phase II trials in mTNBC, were included. RESULTS A meta-analysis of mTNBC subgroups from three phase III trials in 1L MBC reported pooled objective response rate (ORR) of 23%, median overall survival (OS) of 17.5 months, and median progression-free survival (PFS) of 5.4 months with single-agent chemotherapy. In two subgroup analyses from a phase III study and a phase II trial (n = 40 each), median duration of response (DOR) to 1L chemotherapy for mTNBC was 4.4-6.6 months; therefore, responses were not durable. A meta-analysis of seven cohorts showed the pooled ORR for 2L+ chemotherapy was 11% (95% CI, 9-14%). Median DOR to 2L+ chemotherapy in mTNBC was also limited (4.2-5.9 months) per two subgroup analyses from a phase III study. No combination chemotherapy regimens recommended by NCCN v1.2016 for treatment of MBC showed superior OS to single agents. CONCLUSIONS Chemotherapies have limited effectiveness and are associated with unfavorable toxicity profiles, highlighting a considerable unmet medical need for improved therapeutic options in mTNBC. In addition to the recently approved combination of atezolizumab and nab-paclitaxel for PD-L1-positive mTNBC, new treatments resulting in durable clinical responses, prolonged survival, and manageable safety profile would greatly benefit patients with mTNBC.

中文翻译：

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局部复发性无法手术或转移性三阴性乳腺癌患者的当前治疗前景：系统的文献综述。

背景技术转移性三阴性乳腺癌（mTNBC）是一种侵袭性的组织学亚型，预后较差。化疗仍是mTNBC的标准治疗方法，尽管尚未针对该乳腺癌亚型专门批准任何药物。取而代之的是，已批准用于转移性乳腺癌（MBC）的化学疗法用于mTNBC（国家综合癌症网络指南[NCCN] v1.2019）。Atezolizumab联合nab-紫杉醇最近被批准用于程序性死亡配体1（PD-L1）阳性的局部晚期或转移性TNBC。回顾了已发表的历史数据，以表征NCCN推荐（v1.2016）药物作为一线（1L）和二线或以后（2L +）治疗局部复发无法手术或转移性TNBC（在此统称为mTNBC）患者的疗效）。方法进行了系统的文献综述，以NCCN v1.2016指南为基础，研究了mTNBC疗法的临床疗效。包括来自13项研究的数据，这些数据基于MBC的III期临床试验或mTNBC的II期临床试验发表了回顾性mTNBC亚组分析。结果对来自1L MBC的三项III期临床试验的mTNBC亚组进行的荟萃分析报告，总客观缓解率（ORR）为23％，中位总体生存期（OS）为17.5个月，中位无进展生存期（PFS）为5.4个月单药化疗。在一项III期研究和一项II期试验的两个亚组分析中（每组n = 40），mTNBC对1L化疗的中位反应持续时间（DOR）为4.4-6.6个月。因此，回应并不持久。对七个队列的荟萃分析显示，用于2L +化疗的总ORR为11％（95％CI，9-14％）。III期研究的每两个亚组分析中，mTNBC中DOR到2L +化疗的中位值也受到限制（4.2-5.9个月）。NCCN v1.2016建议使用的联合化疗方案未显示优于单药的OS。结论化学疗法的有效性有限，并且与不良的毒性有关，这突显了医学上尚未满足的对mTNBC中改善治疗选择的需求。除了最近批准的atezolizumab和nab-紫杉醇的组合用于PD-L1阳性mTNBC外，新的疗法可产生持久的临床反应，延长的生存期和可控的安全性，这将极大地受益于mTNBC患者。III期研究的每两个亚组分析中，mTNBC中DOR到2L +化疗的中位值也受到限制（4.2-5.9个月）。NCCN v1.2016建议使用的联合化疗方案未显示优于单药的OS。结论化学疗法的有效性有限，并且与不良的毒性有关，这突显了医学上尚未满足的对mTNBC中改善治疗选择的需求。除了最近批准的atezolizumab和nab-紫杉醇的组合用于PD-L1阳性mTNBC外，新的疗法可产生持久的临床反应，延长的生存期和可控的安全性，这将极大地受益于mTNBC患者。III期研究的每两个亚组分析中，mTNBC中DOR到2L +化疗的中位值也受到限制（4.2-5.9个月）。NCCN v1.2016建议使用的联合化疗方案未显示优于单药的OS。结论化学疗法的有效性有限，并且与不良的毒性有关，这突出表明了对mTNBC中改善治疗选择的相当大的医学需求尚未得到满足。除了最近批准的atezolizumab和nab-紫杉醇的组合用于PD-L1阳性mTNBC外，新的疗法可产生持久的临床反应，延长的生存期和可控的安全性，这将极大地受益于mTNBC患者。NCCN v1.2016建议使用的联合化疗方案没有显示出优于单药的OS。结论化学疗法的有效性有限，并且与不良的毒性有关，这突显了医学上尚未满足的对mTNBC中改善治疗选择的需求。除了最近批准的atezolizumab和nab-紫杉醇的组合用于PD-L1阳性mTNBC外，新的疗法可产生持久的临床反应，延长的生存期和可控的安全性，这将极大地受益于mTNBC患者。NCCN v1.2016建议使用的联合化疗方案未显示优于单药的OS。结论化学疗法的有效性有限，并且与不良的毒性有关，这突出表明了对mTNBC中改善治疗选择的相当大的医学需求尚未得到满足。除了最近批准的atezolizumab和nab-紫杉醇的组合用于PD-L1阳性mTNBC外，新的疗法可产生持久的临床反应，延长的生存期和可控的安全性，这将极大地受益于mTNBC患者。