PARP抑制剂目前用于HER2-乳腺癌HER2-乳腺癌的治疗,以及对铂类化疗缓解后的卵巢癌维持治疗[2-4]。为了进一步扩大可能受益于PARP抑制剂的患者人群(例如铂耐药、非BRCA突变的患者),并且避免重复使用铂类化疗的毒性,需要探索有效的无化疗治疗方案。抗血管生成药物可以引起肿瘤微环境缺氧,导致遗传不稳定性和BRCA1/2的下调,从而增强对PARP抑制剂的敏感性[4-7]。在既往研究中,已证明抗血管生成药物联合PARP抑制剂,可改善患者PFS[8-10]。 目前,氟唑帕利和阿帕替尼的口服联合用药正在临床研发中,旨在提高治疗的便利性,规避常规化疗带来的损伤及毒副反应。 研究采用标准的3+3剂量递增设计:氟唑帕利的剂量为40-100mg(bid),阿帕替尼的剂量为250mg、375mg和500mg(qd)。主要终点是确定氟唑帕利联合阿帕替尼治疗的推荐Ⅱ期剂量(RP2D)和耐受性。次要终点包括最佳总体反应、ORR和疾病控制率(DCR),糖类抗原125(CA-125)反应等。 2017年3月17日至2021年3月2日期间,共有52例患者入组:剂量递增队列27例,PK拓展队列25例。其中,包括30例卵巢癌患者和22例三阴性乳腺癌患者。截至2021年8月22日,中位随访时间11.3个月。 在所有剂量水平中,52例患者中5例(9.6%)完全缓解(CR),14例(26.9%)部分缓解(PR),15例(28.8%)疾病稳定(SD)。氟唑帕利100mg联合阿帕替尼500mg最高剂量水平,ORR为50.0%,DCR为62.5%。 作为一家创新型国际化制药企业,恒瑞医药多年来针对中国高发肿瘤领域持续展开技术攻关,在中国获批上市自研创新药13款、引进创新药2款,其中肿瘤创新药达9款。未来,恒瑞医药将继续深入实施科技创新和国际化双轮驱动发展战略,立足民生需求,争分夺秒推进创新药研发,努力研制出更多的新药好药,为守护患者健康生活和生命质量作出更大贡献。 [1] Yaxin Liu, Wei Wang,et al. A phase 1 trial of fuzuloparib in combination with apatinib for advanced ovarian and triple negative breast cancer: efficacy, safety, pharmacokinetics and germline BRCA mutation analysis. [2] Vanacker H, Harter P, Labidi-Galy SI, Banerjee S, Oaknin A, Lorusso D, et al. PARPinhibitors in epithelial ovarian cancer: Actual positioning and future expectations. Cancer Treat Rev. 2021; 99:102255.
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