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三阴性乳腺癌与其他乳腺癌相比，预后较差，而且人类滋养层细胞表面抗原TROP2表达比例较高。戈沙妥珠单抗（拓达维）由1个大分子TROP2抗体沙妥珠单抗与7～8个小分子化疗药伊立替康活性代谢产物戈维替康通过可水解连接分子缀合而成，已被IMMU-132-01、IMMU-132-05（ASCENT）等研究证实对三阴性乳腺癌晚期患者有效，从而两次登顶《新英格兰医学杂志》。不过，这些研究都在欧美国家开展。 相关链接 2023年1月9日，国际抗癌联盟《国际癌症杂志》在线发表中国工程院院士徐兵河、中国医学科学院肿瘤医院马飞、解放军总医院第五医学中心王涛、中山大学肿瘤防治中心王树森、天津医科大学肿瘤医院佟仲生、吉林大学第一医院李薇、湖北省肿瘤医院吴新红、浙江省肿瘤医院王晓稼、辽宁省肿瘤医院孙涛、安徽省立医院潘跃银、中山大学孙逸仙纪念医院姚和瑞、浙江大学医学院附属邵逸夫医院王娴、四川大学华西医院罗婷、西安交通大学第一附属医院杨谨、重庆大学附属肿瘤医院曾晓华、解放军总医院赵卫红等学者的EVER-132-001研究报告，首次探讨了戈沙妥珠单抗对中国三阴性乳腺癌患者的有效性和安全性。 EVER-132-001 (NCT04454437): Sacituzumab Govitecan in Chinese Patients With mTNBC of at Least 2 Prior Treatments (A Phase IIb, Single Arm, Multicenter Trial of Sacituzumab Govitecan in Chinese Patients With Metastatic Triple-negative Breast Cancer Who Received at Least Two Prior Treatments) 该多中心单组二期临床研究于2020年10月23日～2021年1月27日从全国14个研究中心入组中国三阴性乳腺癌晚期既往至少二线（中位四线，多达八线）化疗失败女性患者80例（年龄24～69.9岁，中位47.6岁）每21天的第1天和第8天接受戈沙妥珠单抗10mg/kg直至疾病进展或毒性反应无法耐受。主要终点为由独立评审委员会评定的客观缓解率。次要终点包括：缓解持续期、临床获益率、无进展生存、总生存、安全性。 结果，截至2021年8月6日：
戈沙妥珠单抗相关≥3级治疗期间不良事件发生率为71.3%，最常见中性粒细胞减少（62.5%）、白细胞减少（48.8%）和贫血（21.3%）；6.3%的患者由于治疗期间不良事件而停用戈沙妥珠单抗。 因此，该多中心小样本非对照二期临床研究结果表明，对于中国三阴性乳腺癌晚期多线化疗失败患者，戈沙妥珠单抗临床疗效显著，安全问题基本可控，与欧美患者相比，有效性和安全性大致相似。 据悉，国家药品监督管理局已于2022年6月7日签发注册证（国药准字SJ20220015）正式批准戈沙妥珠单抗（拓达维）进入中国。 Int J Cancer. 2023 Jan 9. IF: 7.316 A phase IIb, single arm, multicenter trial of sacituzumab govitecan in Chinese patients with metastatic triple-negative breast cancer who received at least two prior treatments. Xu B, Ma F, Wang T, Wang S, Tong Z, Li W, Wu X, Wang X, Sun T, Pan Y, Yao H, Wang X, Luo T, Yang J, Zeng X, Zhao W, Cong XJ, Chen J. National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China; The Fifth Medical Center of PLA General Hospital, Beijing, China; Sun Yet-Sen University Cancer Center, Guangzhou, China; Tianjin Medical University Cancer Institute and Hospital, Tianjin, China; The First Hospital of Jilin University, Changchun, China; Hubei Cancer Hospital, Wuhan, China; Zhejiang Cancer Hospital, Hangzhou, China; Liaoning Cancer Hospital &Institute, Shenyang, China; Anhui Provincial Hospital, Hefei, China; Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, China; Sir Run Run Shaw Hospital, Hangzhou, China; West China Hospital, Sichuan University, Chengdu, China; First Affiliated Hospital of Xian Jiaotong University, Xi'an, China; Chongqing University Cancer Hospital, Chongqing, China; Chinese PLA General Hospital, Beijing, China; Everest Medicines, Shanghai, China. Refractory or relapsing metastatic triple-negative breast cancer (mTNBC) has a poor prognosis. Sacituzumab govitecan (SG) is a novel antibody-drug conjugate, targeting human trophoblast cell-surface antigen 2 (Trop-2). This is the first report of SG's efficacy and safety in Chinese patients with mTNBC. EVER-132-001 (NCT04454437) was a multicenter, single-arm, Phase IIb study in Chinese patients with mTNBC who failed ≥2 prior chemotherapy regimens. Eligible patients received 10 mg/kg SG on Days 1 and 8 of each 21-day treatment cycle, until disease progression/unacceptable toxicity. The primary endpoint was objective response rate (ORR) assessed by the Independent Review Committee. Secondary endpoints included: duration of response (DOR), clinical benefit rate (CBR), progression-free survival (PFS), overall survival (OS), and safety. 80 female Chinese patients (median age 47.6 years; range 24-69.9 years) received ≥1 SG dose with a median of 8 treatment cycles by the cutoff date (August 6, 2021). Median number of prior systemic cancer treatments was 4.0 (range 2.0-8.0). ORR and CBR were reported 38.8% (95% confidence interval [CI]: 28.06-50.30) and 43.8% (95% CI: 32.68- 55.30) of patients, respectively. The median PFS was 5.55 months (95% CI: 4.14-N/A). SG-related Grade ≥3 treatment-emergent adverse events (TEAEs) were reported in 71.3%, the most common were neutrophil count decreased (62.5%), white blood cell count decreased (48.8%), and anemia (21.3%); 6.3% discontinued SG because of TEAEs. SG demonstrated substantial clinical activity in heavily pre-treated Chinese patients with mTNBC. The observed safety profile was generally manageable. KEYWORDS: Antibody drug conjugate; China; Sacituzumab govitecan; Triple-negative breast cancer; Trop-2 PMID: 36621000 DOI: 10.1002/ijc.34424         |
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