晚期乳腺癌患者中,有约20%-50%的患者会发生脑部转移[1]。目前乳腺癌脑转移的主要治疗手段仍以放疗或手术的局部治疗为主,药物治疗为辅。因血脑屏障和血肿瘤屏障的存在,许多对乳腺癌颅外转移有效的治疗药物进入颅内的通透性较差,在颅内很难达到有效的药物浓度[2]。乳腺癌脑转移患者普遍预后较差,HER2阴性乳腺癌脑转移则更差[3]:HR阳性/HER2阴性(包括HER2低表达)乳腺癌脑转移患者中位无进展生存期(mPFS)约4-6个月[4-8];而三阴性乳腺癌脑转移患者mPFS仅2.8个月[9]。 近年来,小分子TKI和新型抗体偶联药物(ADC)为HER2阳性乳腺癌脑转移带来了生存获益,但HER2阴性乳腺癌脑转移尚缺乏明确有效的药物治疗方案,全球范围尚无任何药物被批准用于HER2阴性乳腺癌脑转移患者,存在明显未被满足的临床需求。 根据华昊中天新闻稿,优替德隆独特的理化性质以及对P-糖蛋白介导的外排不敏感等优势,使其具备穿透血脑屏障的能力。该特性已通过临床前药物组织分布实验、患者脑肿瘤囊液检测以及多项针对乳腺癌脑转移的临床研究得到充分证实。
在今年ASCO大会上,研究人员首次公布了一项优替德隆联合贝伐珠单抗治疗HER2阴性乳腺癌脑转移临床2期研究数据。该研究共纳入47例患者,中枢神经系统病灶客观缓解率(CNS-ORR)为42.6%,mPFS为7.7个月(其中HR阴性/HER2阴性患者CNS-ORR为55%,mPFS为8.4个月),12个月总生存率达到74.4%,不良事件主要为1~2级。研究表明优替德隆对脑转移灶具有良好的疗效,且安全性可控,为HER2阴性乳腺癌脑转移患者提供了新的治疗选择。 本次获FDA批准的2期临床试验旨在评估优替德隆注射液联合卡培他滨治疗HER2阴性乳腺癌脑转移患者的颅内和全身疗效及安全性。该研究计划在美国10-15家中心开展,采用Simon两阶段设计,共拟入组约120例受试者,主要研究终点为CNS-ORR;次要研究终点包括PFS、持续缓解时间(DOR)和总生存期(OS)等。
参考资料:
[1] Lin, N. U., Gaspar, L. E. & Soffietti, R. Breast cancer in the central nervous system: multidisciplinary considerations and management. Am. Soc. Clin. Oncol. Educ. Book 37, 45–56 (2017).
[2] Arvanitis, Costas D et al. “The blood-brain barrier and blood-tumour barrier in brain tumours and metastases.” Nature reviews. Cancer vol. 20, 1 (2020): 26-41. doi:10.1038/s41568-019-0205-x
[3] Darlix A, Louvel G, et al. Impact of breast cancer molecular subtypes on the incidence, kinetics and prognosis of central nervous system metastases in a large multicentre real-life cohort. Br J Cancer. 2019 Dec; 121(12): 991-1000.
[4] Leone, J.P. Emblem, K.E et al. Phase II trial of carboplatin and bevacizumab in patients with breast cancer brain metastases. Breast Cancer Res. 2020, 22, 131.
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[8]Nadia Harbeck, et al. Trastuzumab deruxtecan vs treatment of physician’s choice in patients with HER2-low unresectable and/or metastatic breast cancer: Subgroup analyses from DESTINY-Breast04. 2022 SABCS. P1-11-01
[9] Diéras V, Weaver R, et al. Abstract Pd13-07: Subgroup analysis of patients with brain metastases from the phase 3 ascent study of sacituzumab govitecan versus chemotherapy in metastatic triple-negative breast cancer. Cancer Res (2021)81 (4_Supplement): PD13–07-PD13-07
[10]FDA批准华昊中天优替德隆注射液治疗乳腺癌脑转移临床试验. Retrieved July 02 , 2024, from https://mp.weixin.qq.com/s/4Oj8ZfgTOlARZb2Cj_dV3w
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