Sacituzumab govitecan demonstrated significant progression-free survival benefit over chemotherapy in the phase 3 TROPiCS-02 trial in patients with pretreated, endocrine-resistant hormone receptor-positive, human epidermal growth factor receptor 2-negative (HR+ and HER2–) metastatic breast cancer with limited treatment options. Here, we report the protocol-specified final analysis of overall survival and endpoints by trophoblast cell-surface antigen 2 (Trop-2) expression and other variables. In this randomised, open-label, multicentre, phase 3 trial, which took place in 91 centres across North America (the USA and Canada) and Europe (Belgium, France, Germany, Italy, the Netherlands, Spain, and the UK), patients were randomly assigned (1:1) to receive sacituzumab govitecan or chemotherapy (eribulin, vinorelbine, capecitabine, or gemcitabine). Patients had confirmed HR+ and HER2– locally recurrent inoperable or metastatic breast cancer and had received at least one previous endocrine therapy, a taxane, and a CDK4/6 inhibitor in any setting and two to four previous chemotherapy regimens for metastatic disease. The primary endpoint was progression-free survival (previously reported and not included in this analysis), and secondary endpoints included overall survival, objective response rate (ORR), and patient-reported outcomes. Overall survival was assessed using stratified log-rank tests and Cox regression. Trop-2 expression was assessed in tumour tissue by immunohistochemistry. In the statistical testing hierarchy, ORR and patient-reported outcomes were tested sequentially if overall survival was significant. This study is registered with , . At the data cutoff date of July 1, 2022, 543 of 776 screened patients were randomly assigned between May 30, 2019, and April 5, 2021, with 272 patients in the sacituzumab govitecan group and 271 patients in the chemotherapy group. With a 12·5-month (IQR 6·4–18·8) median follow-up, 390 deaths occurred among 543 patients. Overall survival was significantly improved with sacituzumab govitecan versus chemotherapy (median 14·4 months [95% CI 13·0–15·7] 11·2 months [10·1–12·7]; hazard ratio [HR] 0·79, 95% CI 0·65–0·96; p=0·020); survival benefit was consistent across Trop-2 expression-level subgroups. ORR was significantly improved with sacituzumab govitecan compared with chemotherapy (57 [21%] patients 38 [14%]; odds ratio 1·63 [95% CI 1·03–2·56]; p=0·035), as was time to deterioration of global health status and quality of life (median 4·3 months 3·0 months; HR 0·75 [0·61–0·92]; p=0·0059) and fatigue (median 2·2 months 1·4 months; HR 0·73 [0·60–0·89]; p=0·0021). The safety profile of sacituzumab govitecan was consistent with previous studies (including the TROPiCS-02 primary analysis and the ASCENT trial). One fatal adverse event (septic shock caused by neutropenic colitis) was determined to be related to sacituzumab govitecan treatment. Sacituzumab govitecan demonstrated statistically significant and clinically meaningful benefit over chemotherapy, with a 3·2-month median overall survival improvement and a manageable safety profile. These data support sacituzumab govitecan as a new treatment option for patients with pretreated, endocrine-resistant HR+ and HER2– metastatic breast cancer. Gilead Sciences.

中文翻译：

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sacituzumab govitecan 在激素受体阳性和人表皮生长因子受体 2 阴性转移性乳腺癌 (TROPiCS-02) 中的总生存期：一项随机、开放标签、多中心、3 期试验

在 3 期 TROPiCS-02 试验中，Sacituzumab govitecan 与化疗相比，在经治疗的内分泌抵抗激素受体阳性、人表皮生长因子受体 2 阴性（HR+ 和 HER2-）转移性乳腺癌患者中表现出显着的无进展生存获益。治疗选择有限。在这里，我们报告了根据滋养层细胞表面抗原 2 (Trop-2) 表达和其他变量对总体生存和终点进行的方案指定的最终分析。这项随机、开放标签、多中心、3 期试验在北美（美国和加拿大）和欧洲（比利时、法国、德国、意大利、荷兰、西班牙和英国）的 91 个中心进行，患者被随机分配（1:1）接受 sacituzumab govitecan 或化疗（艾日布林、长春瑞滨、卡培他滨或吉西他滨）。患者已确诊为 HR+ 和 HER2- 局部复发性不可手术或转移性乳腺癌，并且在任何情况下均接受过至少一种既往内分泌治疗、紫杉烷和 CDK4/6 抑制剂，以及既往接受过两到四种针对转移性疾病的化疗方案。主要终点是无进展生存期（之前报告过，未包含在本次分析中），次要终点包括总生存期、客观缓解率 (ORR) 和患者报告的结果。使用分层对数秩检验和 Cox 回归评估总体生存率。通过免疫组织化学评估肿瘤组织中的 Trop-2 表达。在统计测试层次中，如果总生存率显着，则按顺序测试 ORR 和患者报告的结果。这项研究已在 注册。截至数据截止日期2022年7月1日，776名筛查患者中的543名在2019年5月30日至2021年4月5日期间被随机分配，其中272名患者属于sacituzumab govitecan组，271名患者属于化疗组。中位随访时间为 12·5 个月（IQR 6·4–18·8），543 名患者中有 390 人死亡。与化疗相比，sacituzumab govitecan 的总生存期显着改善（中位生存期 14·4 个月 [95% CI 13·0–15·7] 11·2 个月 [10·1–12·7]；风险比 [HR] 0·79 ，95% CI 0·65–0·96；p=0·020)；Trop-2 表达水平亚组的生存获益是一致的。与化疗相比，sacituzumab govitecan 的 ORR 显着改善（57 [21%] 患者 38 [14%]；比值比 1·63 [95% CI 1·03–2·56]；p=0·035），全球健康状况和生活质量恶化的时间（中位 4·3 个月 3·0 个月；HR 0·75 [0·61–0·92]；p=0·0059）和疲劳（中位 2·2 个月） 1·4 个月；HR 0·73 [0·60–0·89]；p=0·0021）。sacituzumab govitecan 的安全性与之前的研究（包括 TROPiCS-02 初步分析和 ASCENT 试验）一致。一项致命不良事件（由中性粒细胞减少性结肠炎引起的败血性休克）被确定与 sacituzumab govitecan 治疗有关。Sacituzumab govitecan 表现出比化疗具有统计学显着性和临床意义的益处，中位总生存期延长 3·2 个月，安全性可控。这些数据支持 sacituzumab govitecan 作为经过治疗的内分泌耐药 HR+ 和 HER2- 转移性乳腺癌患者的新治疗选择。吉利德科学。