Efficacy and Safety of Anti-Trop-2 Antibody Drug Conjugate Sacituzumab Govitecan (IMMU-132) in Heavily Pretreated Patients With Metastatic Triple-Negative Breast Cancer
Efficacy and Safety of Anti-Trop-2 Antibody Drug Conjugate Sacituzumab Govitecan (IMMU-132) in Heavily Pretreated Patients With Metastatic Triple-Negative Breast Cancer
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DOI：
10.1200/jco.2016.70.8297
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发表时间：
2017-07-01
影响因子：
45.3
通讯作者：
Vahdat, Linda T.
中科院分区：
文献类型：
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作者：
Bardia, Aditya;Mayer, Ingrid A.;Vahdat, Linda T.
目的Trop-2在大多数三阴性乳腺癌（triple-negative breast cancer，TNBC）中表达，可能成为抗体-药物偶联物的潜在靶点。Sacituzumab govitecan，抗体-药物缀合物，靶向Trop-2选择性递送SN-38，irinotecan.Patients和MethodsWe的活性代谢产物评估sacituzumab govitecan在单臂，多中心试验中复发/难治性转移性TNBC患者谁收到了10毫克/公斤的起始剂量在第1和第8天的21天的重复周期。主要终点是安全性和客观反应率;次要终点是无进展生存期和总生存期。（范围，1 - 12）自诊断以来，确认的客观缓解率为30%（部分缓解，n = 19;完全缓解，n = 2），中位缓解持续时间为8.9（95%CI，6.1 ~ 11.3）个月，临床获益率（完全缓解+部分缓解+病情稳定>= 6个月）为46%。这些反应发生较早，中位发病时间为1.9个月。中位无进展生存期为6.0（95% CI，5.0 - 7.3）个月，中位总生存期为16.6（95% CI，11.1 - 20.6）个月。≥ 3级的不良事件包括中性粒细胞减少（39%）、白细胞减少（16%）、贫血（14%）和腹泻（13%）;发热性中性粒细胞减少的发生率为7%。通过免疫组织化学，大多数存档肿瘤标本（88%）为Trop-2中度至强阳性。没有中和抗体的ADC或抗体被检测到，尽管重复cyclesdeveloped.ConclusionSacituzumab govitecan耐受性良好，诱导早期和持久的反应，在大量预处理的转移性TNBC患者。作为治疗靶点和预测生物标志物，Trop-2值得进一步研究。(C)2017年美国临床肿瘤学会
PurposeTrop-2, expressed in most triple-negative breast cancers (TNBCs), may be a potential target for antibody-drug conjugates. Sacituzumab govitecan, an antibody-drug conjugate, targets Trop-2 for the selective delivery of SN-38, the active metabolite of irinotecan.Patients and MethodsWe evaluated sacituzumab govitecan in a single-arm, multicenter trial in patients with relapsed/refractory metastatic TNBC who received a 10 mg/kg starting dose on days 1 and 8 of 21-day repeated cycles. The primary end points were safety and objective response rate; secondary end points were progression-free survival and overall survival.ResultsIn 69 patients who received a median of five prior therapies (range, one to 12) since diagnosis, the confirmed objective response rate was 30% (partial response, n = 19; complete response, n = 2), the median response duration was 8.9 (95% CI, 6.1 to 11.3) months, and the clinical benefit rate (complete response + partial response + stable disease >= 6 months) was 46%. These responses occurred early, with a median onset of 1.9 months. Median progression-free survival was 6.0 (95% CI, 5.0 to 7.3) months, and median overall survival was 16.6 (95% CI, 11.1 to 20.6) months. Grade >= 3 adverse events included neutropenia (39%), leukopenia (16%), anemia (14%), and diarrhea (13%); the incidence of febrile neutropenia was 7%. The majority of archival tumor specimens (88%) were moderately to strongly positive for Trop-2 by immunohistochemistry. No neutralizing antibodies to the ADC or antibody were detected, despite repeated cycles developed.ConclusionSacituzumab govitecan was well tolerated and induced early and durable responses in heavily pretreated patients with metastatic TNBC. As a therapeutic target and predictive biomarker, Trop-2 warrants further research. (C) 2017 by American Society of Clinical Oncology