在既往治疗的激素受体阳性/HER2 阴性转移性乳腺癌中应用 sacituzumab govitecan：一项 I/II 期、单臂、篮子试验的最终结果。
Sacituzumab govitecan in previously treated hormone receptor-positive/HER2-negative metastatic breast cancer: final results from a phase I/II, single-arm, basket trial.
机构信息
Department of Medicine, Division of Hematology/Oncology, Columbia University Irving Medical Center-Herbert Irving Comprehensive Cancer Center, New York, USA.
Department of Medicine, Medical Oncology, University of Colorado Cancer Center, Aurora, USA.
出版信息
Ann Oncol. 2020 Dec;31(12):1709-1718. doi: 10.1016/j.annonc.2020.09.004. Epub 2020 Sep 15.
BACKGROUND
Trophoblast cell-surface antigen-2 (Trop-2) is expressed in epithelial cancers, including hormone receptor-positive (HR+) metastatic breast cancer (mBC). Sacituzumab govitecan (SG; Trodelvy®) is an antibody-drug conjugate composed of a humanized anti-Trop-2 monoclonal antibody coupled to SN-38 at a high drug-to-antibody ratio via a unique hydrolyzable linker that delivers SN-38 intracellularly and in the tumor microenvironment. SG was granted accelerated FDA approval for metastatic triple-negative BC treatment in April 2020.
PATIENTS AND METHODS
We analyzed a prespecified subpopulation of patients with HR+/human epidermal growth factor receptor 2-negative (HER2-) HR+/HER2- mBC from the phase I/II, single-arm trial (NCT01631552), who received intravenous SG (10 mg/kg) and whose disease progressed on endocrine-based therapy and at least one prior chemotherapy for mBC. End points included objective response rate (ORR; RECIST version 1.1) assessed locally, duration of response (DOR), clinical benefit rate, progression-free survival (PFS), overall survival (OS), and safety.
RESULTS
Fifty-four women were enrolled between 13 February 2015 and 1 June 2017. Median (range) age was 54 (33-79) years and all received at least two prior lines of therapy for mBC. At data cut-off (1 March 2019), 12 patients were still alive. Key grade ≥3 treatment-related toxicities included neutropenia (50.0%), anemia (11.1%), and diarrhea (7.4%). Two patients discontinued treatment due to treatment-related adverse events. No treatment-related deaths occurred. At a median follow-up of 11.5 months, the ORR was 31.5% [95% confidence interval (CI), 19.5%-45.6%; 17 partial responses]; median DOR was 8.7 months (95% CI 3.7-12.7), median PFS was 5.5 months (95% CI 3.6-7.6), and median OS was 12 months (95% CI 9.0-18.2).
CONCLUSIONS
SG shows encouraging activity in patients with pretreated HR+/HER2- mBC and a predictable, manageable safety profile. Further evaluation in a randomized phase III trial (TROPiCS-02) is ongoing (NCT03901339).
TRIAL REGISTRATION
ClinicalTrials.gov NCT01631552; https://clinicaltrials.gov/ct2/show/NCT01631552.
背景
滋养细胞表面抗原-2（Trop-2）在包括激素受体阳性（HR+）转移性乳腺癌（mBC）在内的上皮癌中表达。Sacituzumab govitecan（SG；Trodelvy®）是一种抗体-药物偶联物，由与人 Trop-2 单克隆抗体通过独特的可水解接头连接而成，接头通过高药物抗体比将 SN-38 连接到抗体上，从而将 SN-38 细胞内和肿瘤微环境中。SG 于 2020 年 4 月被 FDA 加速批准用于治疗转移性三阴性乳腺癌。
患者和方法
我们分析了来自 I/II 期、单臂试验（NCT01631552）的 HR+/人表皮生长因子受体 2 阴性（HER2-）HR+/HER2-mBC 患者的一个预设亚组，这些患者接受静脉注射 SG（10mg/kg），并且在接受内分泌治疗和至少一种用于 mBC 的先前化疗后疾病进展。终点包括根据 RECIST 版本 1.1 评估的客观缓解率（ORR）、缓解持续时间（DOR）、临床获益率、无进展生存期（PFS）、总生存期（OS）和安全性。
结果
2015 年 2 月 13 日至 2017 年 6 月 1 日期间共纳入 54 名女性。中位（范围）年龄为 54 岁（33-79 岁），所有患者均接受过至少两种 mBC 的先前治疗。在数据截止日期（2019 年 3 月 1 日），仍有 12 名患者存活。关键的≥3 级治疗相关毒性包括中性粒细胞减少症（50.0%）、贫血（11.1%）和腹泻（7.4%）。两名患者因治疗相关不良事件停止治疗。无治疗相关死亡。中位随访 11.5 个月时，ORR 为 31.5%（95%CI，19.5%-45.6%；17 例部分缓解）；中位 DOR 为 8.7 个月（95%CI，3.7-12.7），中位 PFS 为 5.5 个月（95%CI，3.6-7.6），中位 OS 为 12 个月（95%CI，9.0-18.2）。
结论
SG 在预处理的 HR+/HER2-mBC 患者中显示出令人鼓舞的疗效，且具有可预测、可管理的安全性特征。一项正在进行的随机 III 期试验（TROPiCS-02）正在评估（NCT03901339）。
试验注册
ClinicalTrials.gov NCT01631552；https://clinicaltrials.gov/ct2/show/NCT01631552。
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