Clinical trials of immunotherapy in triple-negative breast cancer

被引:35
作者
Howard, Frederick M. [1 ]
Pearson, Alexander T. [1 ]
Nanda, Rita [1 ]
机构
[1] Univ Chicago, Med & Biol Sci, Dept Med, Sect Hematol Oncol, 5841 S Maryland Ave MC 2115, Chicago, IL 60637 USA
基金
美国国家卫生研究院;
关键词
Triple-negative breast cancer; Immunotherapy; Checkpoint blockade; Clinical Trials; Atezolizumab; Pembrolizumab; PEMBROLIZUMAB PLUS CHEMOTHERAPY; TUMOR-INFILTRATING LYMPHOCYTES; REGULATORY T-CELLS; PHASE-III; HIGH-RISK; ADAPTIVE RANDOMIZATION; PD-L1; EXPRESSION; DOUBLE-BLIND; OPEN-LABEL; IMMUNITY;
D O I
10.1007/s10549-022-06665-6
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Purpose Immunotherapy has started to transform the treatment of triple-negative breast cancer (TNBC), in part due to the unique immunogenicity of this breast cancer subtype. This review summarizes clinical studies of immunotherapy in advanced and early-stage TNBC. Findings Initial studies of checkpoint blockade monotherapy demonstrated occasional responses, especially in patients with untreated programmed death-ligand 1 (PD-L1) positive advanced TNBC, but failed to confirm a survival advantage over chemotherapy. Nonetheless, pembrolizumab monotherapy has tumor agnostic approval for microsatellite instability-high or high tumor mutational burden cancers, and thus can be considered for select patients with advanced TNBC. Combination chemoimmunotherapy approaches have been more successful, and pembrolizumab is approved for PD-L1 positive advanced TNBC in combination with chemotherapy. This success has been translated to the curative setting, where pembrolizumab is now approved in combination with neoadjuvant chemotherapy for high-risk early-stage TNBC. Conclusion Immunotherapy has been a welcome addition to the growing armamentarium for TNBC, but responses remain limited to a subset of patients. Innovative strategies are under investigation in an attempt to induce immune responses in resistant tumors-with regimens incorporating small-molecule inhibitors, novel immune checkpoint targets, and intratumoral injections that directly alter the tumor microenvironment. As the focus shifts toward the use of immunotherapy for early-stage TNBC, it will be critical to identify those who derive the most benefit from treatment, given the potential for irreversible autoimmune toxicity and the lack of predictive accuracy of PD-L1 expression in the early-stage setting.
引用
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页码:1 / 15
页数:15
相关论文
共 99 条
[1]   Selective Inhibition of Regulatory T Cells by Targeting the PI3K-Akt Pathway [J].
Abu-Eid, Rasha ;
Samara, Raed N. ;
Ozbun, Laurent ;
Abdalla, Maher Y. ;
Berzofsky, Jay A. ;
Friedman, Kevin M. ;
Mkrtichyan, Mikayel ;
Khleif, Samir N. .
CANCER IMMUNOLOGY RESEARCH, 2014, 2 (11) :1080-1089
[2]   Patient-reported outcomes from the phase III IMpassion130 trial of atezolizumab plus nab-paclitaxel in metastatic triple-negative breast cancer [J].
Adams, S. ;
Dieras, V. ;
Barrios, C. H. ;
Winer, E. P. ;
Schneeweiss, A. ;
Iwata, H. ;
Loi, S. ;
Patel, S. ;
Henschel, V. ;
Chui, S. Y. ;
Rugo, H. S. ;
Emens, L. A. ;
Schmid, P. .
ANNALS OF ONCOLOGY, 2020, 31 (05) :582-589
[3]  
Adams S, 2019, ANN ONCOL, V30, P405, DOI [10.1093/annonc/mdy518, 10.1093/annonc/mdy517]
[4]  
Adams S, 2020, J CLIN ONCOL, V38
[5]   Atezolizumab Plus nab-Paclitaxel in the Treatment of Metastatic Triple-Negative Breast Cancer With 2-Year Survival Follow-up A Phase 1b Clinical Trial [J].
Adams, Sylvia ;
Diamond, Jennifer R. ;
Hamilton, Erika ;
Pohlmann, Paula R. ;
Tolaney, Sara M. ;
Chang, Ching-Wei ;
Zhang, Wei ;
Iizuka, Koho ;
Foster, Paul G. ;
Molinero, Luciana ;
Funke, Roel ;
Powderly, John .
JAMA ONCOLOGY, 2019, 5 (03) :334-342
[6]   Prognostic Value of Tumor-Infiltrating Lymphocytes in Triple-Negative Breast Cancers From Two Phase III Randomized Adjuvant Breast Cancer Trials: ECOG 2197 and ECOG 1199 [J].
Adams, Sylvia ;
Gray, Robert J. ;
Demaria, Sandra ;
Goldstein, Lori ;
Perez, Edith A. ;
Shulman, Lawrence N. ;
Martino, Silvana ;
Wang, Molin ;
Jones, Vicky E. ;
Saphner, Thomas J. ;
Wolff, Antonio C. ;
Wood, William C. ;
Davidson, Nancy E. ;
Sledge, George W. ;
Sparano, Joseph A. ;
Badve, Sunil S. .
JOURNAL OF CLINICAL ONCOLOGY, 2014, 32 (27) :2959-+
[7]  
Amy Jo Chien, EVALUATION INTRATUMO
[8]   LCCC 1525: A phase II study of a priming dose of cyclophosphamide prior to pembrolizumab to treat metastatic triple negative breast cancer (mTNBC) [J].
Anders, C. K. ;
Moore, D. ;
Sambade, M. ;
Cuaboy, L. ;
Garrett, A. ;
Woodcock, M. ;
McKinnon, K. ;
Cowens, K. ;
Bortone, D. ;
Calhoun, B. ;
Carey, L. ;
Dees, C. ;
Jolly, T. ;
Muss, H. ;
Reeder-Hayes, K. ;
Kaltman, R. ;
Jankowitz, R. ;
Gudena, V. ;
Olajide, O. ;
Perou, C. ;
Vincent, B. ;
Serody, J. .
CANCER RESEARCH, 2019, 79 (04)
[9]   LAG3 (CD223) as a cancer immunotherapy target [J].
Andrews, Lawrence P. ;
Marciscano, Ariel E. ;
Drake, Charles G. ;
Vignali, Dario A. A. .
IMMUNOLOGICAL REVIEWS, 2017, 276 (01) :80-96
[10]  
[Anonymous], ABSTRACT PD1 03 MULT