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Frontiers of Medicine

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Front. Med.    2021, Vol. 15 Issue (1) : 1-10    https://doi.org/10.1007/s11684-020-0741-5
REVIEW
Progress in systemic therapy for triple-negative breast cancer
Hongnan Mo, Binghe Xu()
Department of Medical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China
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Abstract

Triple-negative breast cancer (TNBC) is the most aggressive subtype of breast cancer with a heterogeneous genetic profile. Chemotherapy exhibits substantial activity in a small subset of these patients. Drug resistance is inevitable. Major progress has been made in the genetic analysis of TNBC to identify novel targets and increase the precision of therapeutic intervention. Such progress has translated into major advances in treatment strategies, including modified chemotherapy approaches, immune checkpoint inhibitors, and targeted therapeutic drugs. All of these strategies have been evaluated in clinical trials. Nevertheless, patient selection remains a considerable challenge in clinical practice.
Keywords triple-negative breast cancer      immunotherapy      targeted therapy     
Corresponding Author(s): Binghe Xu   
Just Accepted Date: 19 April 2020   Online First Date: 12 August 2020    Issue Date: 11 February 2021
 Cite this article:   
Hongnan Mo,Binghe Xu. Progress in systemic therapy for triple-negative breast cancer[J]. Front. Med., 2021, 15(1): 1-10.
 URL:  
https://academic.hep.com.cn/fmd/EN/10.1007/s11684-020-0741-5
https://academic.hep.com.cn/fmd/EN/Y2021/V15/I1/1
Fig.1  Overview of recent improvements in systemic treatment for patients with metastatic TNBC. PARP, poly ADP (adenosine diphosphate)-ribose polymerase; HRD, homologous recombination deficiency; TILs, tumor-infiltrating lymphocytes.
Drug Patients Intervention Efficacy Identifier
Pembrolizumab
27 Advanced PD-L1+TNBC Pembrolizumab 10 mg/kg Q2W ORR, 18.5%
mPFS, 1.9 months
mOS, 11.2 months		 NCT01848834
Ref [45]
170 Advanced, pretreated TNBC, 61.8% PD-L1+ Pembrolizumab 200 mg Q3W ORR, 5.3%
mPFS, 2.0 months
mOS, 9.0 months		 NCT02447003
Ref [43]
84 Advanced, untreated PD-L1+ ?TNBC Pembrolizumab 200 mg Q3W ORR, 21.4%
mPFS, 2.1 months
mOS, 18.0 months		 NCT02447003
Ref [46]
107 Advanced TNBC, ≤2 prior ?lines of chemotherapy Eribulin+ pembrolizumab
?200 mg Q3W		 ORR, 25.6%
mPFS, 4.1 months
mOS, inestimable		 NCT02513472
Ref [47]
Nivolumab
67 Advanced TNBC Irradiation, CTX, cisplatin or ?doxorubicin, or no induction, ?followed by nivolumab ?3 mg/kg Q2W ORR, 20% (overall), 8% (irradiation), ?8% (CTX), 23% (cisplatin), 35% ?(doxorubicin), 17% (no induction) NCT02499367
Ref [48]
Atezolizumab
116 Advanced TNBC Atezolizumab 15 or 20 mg/kg, ?or 1200 mg, Q3W ORR, 10%
mPFS, 1.4 months
mOS, 8.9 months		 NCT01375842
Ref [49]
451 Advanced, untreated TNBC, ?40.9% PD-L1 + Nab-paclitaxel ± atezolizumab
?840 mg Q2W		 ORR, 56.0%
mPFS, 7.2 months
mOS, 21.3 months		 NCT02425891
Ref [41]
Avelumab
58 Advanced, pretreated TNBC Avelumab
?10 mg/kg Q2W		 ORR, 5.2%
mPFS, 5.9 months
mOS, 9.2 months		 NCT01772004
Ref [42]
Tab.1  Efficacy of immune checkpoint inhibitors in TNBC clinical trials
Category Intervention Biomarker eligibility Phase Identifier
PI3Ka inhibitor Alpelisib+ enzalutamide Androgen receptor and PTEN positive I NCT03207529
PI3Kb inhibitor AZD8186+ docetaxel PTEN or PIK3CB mutated I NCT03218826
PI3Kg inhibitor IPI-549 Not required I NCT02637531
PI3K/mTOR inhibitor PF-05212384+ docetaxel/cisplatin/ dacomitinib Not required I NCT01920061
pan-Akt inhibitor Ipatasertib+ carboplatin±paclitaxel Not required I NCT03853707
pan-Akt inhibitor Ipatasertib+ paclitaxel /placebo PIK3CA/AKT1/PTEN-Altered III NCT03337724
Akt/ERK inhibitor ONC201 Not required II NCT03733119
Tab.2  Ongoing clinical trials of PI3K-AKT-mTOR pathway inhibitors in TNBC
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