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三陰性乳腺癌與其他乳腺癌相比，預(yù)后較差，而且人類滋養(yǎng)層細胞表面抗原TROP2表達比例較高。戈沙妥珠單抗（拓達維）由1個大分子TROP2抗體沙妥珠單抗與7～8個小分子化療藥伊立替康活性代謝產(chǎn)物戈維替康通過可水解連接分子綴合而成，已被IMMU-132-01、IMMU-132-05（ASCENT）等研究證實對三陰性乳腺癌晚期患者有效，從而兩次登頂《新英格蘭醫(yī)學(xué)雜志》。不過，這些研究都在歐美國家開展。 相關(guān)鏈接 2023年1月9日，國際抗癌聯(lián)盟《國際癌癥雜志》在線發(fā)表中國工程院院士徐兵河、中國醫(yī)學(xué)科學(xué)院腫瘤醫(yī)院馬飛、解放軍總醫(yī)院第五醫(yī)學(xué)中心王濤、中山大學(xué)腫瘤防治中心王樹森、天津醫(yī)科大學(xué)腫瘤醫(yī)院佟仲生、吉林大學(xué)第一醫(yī)院李薇、湖北省腫瘤醫(yī)院吳新紅、浙江省腫瘤醫(yī)院王曉稼、遼寧省腫瘤醫(yī)院孫濤、安徽省立醫(yī)院潘躍銀、中山大學(xué)孫逸仙紀念醫(yī)院姚和瑞、浙江大學(xué)醫(yī)學(xué)院附屬邵逸夫醫(yī)院王嫻、四川大學(xué)華西醫(yī)院羅婷、西安交通大學(xué)第一附屬醫(yī)院楊謹、重慶大學(xué)附屬腫瘤醫(yī)院曾曉華、解放軍總醫(yī)院趙衛(wèi)紅等學(xué)者的EVER-132-001研究報告，首次探討了戈沙妥珠單抗對中國三陰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) 該多中心單組二期臨床研究于2020年10月23日～2021年1月27日從全國14個研究中心入組中國三陰性乳腺癌晚期既往至少二線（中位四線，多達八線）化療失敗女性患者80例（年齡24～69.9歲，中位47.6歲）每21天的第1天和第8天接受戈沙妥珠單抗10mg/kg直至疾病進展或毒性反應(yīng)無法耐受。主要終點為由獨立評審委員會評定的客觀緩解率。次要終點包括：緩解持續(xù)期、臨床獲益率、無進展生存、總生存、安全性。 結(jié)果，截至2021年8月6日：
戈沙妥珠單抗相關(guān)≥3級治療期間不良事件發(fā)生率為71.3%，最常見中性粒細胞減少（62.5%）、白細胞減少（48.8%）和貧血（21.3%）；6.3%的患者由于治療期間不良事件而停用戈沙妥珠單抗。 因此，該多中心小樣本非對照二期臨床研究結(jié)果表明，對于中國三陰性乳腺癌晚期多線化療失敗患者，戈沙妥珠單抗臨床療效顯著，安全問題基本可控，與歐美患者相比，有效性和安全性大致相似。 據(jù)悉，國家藥品監(jiān)督管理局已于2022年6月7日簽發(fā)注冊證（國藥準字SJ20220015）正式批準戈沙妥珠單抗（拓達維）進入中國。 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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