Kagihara Jodi A, Andress Michelle, Diamond Jennifer R
Division of Medical Oncology, University of Colorado Anschutz Medical Campus, Aurora, United States of America.
Department of Pharmacology, University of Colorado Anschutz Medical Campus, Aurora, United States of America.
Expert Rev Precis Med Drug Dev. 2020;5(2):59-65. doi: 10.1080/23808993.2020.1730694. Epub 2020 Feb 20.
Breast cancer is the most common malignancy in women in the United States and triple-negative breast cancer (TNBC) accounts for 15-20%. The standard of care for metastatic TNBC has been limited to cytotoxic chemotherapy with modest efficacy. TNBC is associated with high levels of tumor-infiltrating lymphocytes and PD-L1 expression, supporting the investigation of immune checkpoint inhibitors in this breast cancer subtype.
This review summarizes the clinical data supporting the use of atezolizumab and nab-paclitaxel in the treatment of metastatic PD-L1-positive TNBC. It examines the pharmacology and toxicity profile of the combination in patients with metastatic TNBC.
The addition of atezolizumab to nab-paclitaxel prolonged progression-free survival in both the intention-to-treat and PD-L1-positive subgroups in the first line setting in patients with metastatic TNBC. The IMpassion 130 trial led to FDA-approval of this combination in patients with PD-L1-positive, metastatic TNBC and represents the first approval of immunotherapy for TNBC. This work supports ongoing investigations of other immunotherapy combinations in TNBC, predictive biomarker development and immunotherapy in patients with early stage TNBC. Immunotherapy combinations in TNBC have the potential to lead to improved survival in this group of patients with high risk disease.
乳腺癌是美国女性中最常见的恶性肿瘤，三阴性乳腺癌（TNBC）占15%-20%。转移性TNBC的标准治疗一直局限于疗效一般的细胞毒性化疗。TNBC与高水平的肿瘤浸润淋巴细胞和PD-L1表达相关，这支持了对这种乳腺癌亚型进行免疫检查点抑制剂的研究。
本综述总结了支持阿特珠单抗和纳米白蛋白结合型紫杉醇用于治疗转移性PD-L1阳性TNBC的临床数据。它研究了该联合用药在转移性TNBC患者中的药理学和毒性特征。
在转移性TNBC患者的一线治疗中，将阿特珠单抗添加到纳米白蛋白结合型紫杉醇中，在意向性治疗和PD-L1阳性亚组中均延长了无进展生存期。IMpassion 130试验导致美国食品药品监督管理局（FDA）批准该联合用药用于PD-L1阳性转移性TNBC患者，这是TNBC免疫疗法的首个获批。这项工作支持正在进行的TNBC其他免疫疗法联合用药研究、预测性生物标志物开发以及早期TNBC患者的免疫治疗。TNBC中的免疫疗法联合用药有可能提高这类高危疾病患者的生存率。
