Sato Sho, Shoji Tadahiro, Jo Ami, Otsuka Haruka, Abe Marina, Tatsuki Shunsuke, Chiba Yohei, Takatori Eriko, Kaido Yoshitaka, Nagasawa Takayuki, Kagabu Masahiro, Baba Tsukasa
Department of Obstetrics and Gynecology, Iwate Medical University, Yahaba 028-3694, Iwate, Japan.
Cancers (Basel). 2024 Jul 15;16(14):2545. doi: 10.3390/cancers16142545.
Ovarian cancer (OC), accounting for approximately 200,000 deaths worldwide annually, is a heterogeneous disease showing major differences in terms of its incidence, tumor behavior, and outcomes across histological subtypes. In OC, primary chemotherapy, paclitaxel carboplatin, bevacizumab, and PARP inhibitors have shown prolonged progression-free survival and a favorable overall response rate compared to conventional treatments. However, treatment options for platinum-resistant recurrence cases are limited, with no effective therapies that significantly prolong the prognosis. Recently, mirvetuximab soravtansine, an alpha-folate receptor (FRα)-targeted antibody-drug conjugate (ADC), was approved by the US Food and Drug Administration for patients with FRα-positive recurrent epithelial OC (EOC). This approval was based on a Phase II study, which demonstrated its efficacy in such patients. ADCs comprise an antibody, a linker, and a payload, representing new concept agents without precedence. Advanced clinical studies are developing ADCs for patients with OC, targeting solid tumors such as gynecologic cancer. Ongoing clinical trials are evaluating ADCs targeting FRα and human epidermal growth factor receptor 2, trophoblast cell surface antigen-2, sodium-dependent phosphate transport protein 2B, and cadherin-6 in Phase II/III studies. In this review, we summarize the existing evidence supporting the use of ADCs in OC, discuss ongoing clinical trials and preclinical studies, and explore the potential of these innovative agents to address the challenges in OC treatment.
卵巢癌(OC)每年在全球导致约20万人死亡,是一种异质性疾病,在组织学亚型的发病率、肿瘤行为和预后方面存在重大差异。在OC中,与传统治疗相比,一线化疗、紫杉醇联合卡铂、贝伐单抗和聚腺苷二磷酸核糖聚合酶(PARP)抑制剂已显示出无进展生存期延长和总体缓解率良好。然而,铂耐药复发病例的治疗选择有限,没有能显著延长预后的有效疗法。最近,mirvetuximab soravtansine,一种靶向α-叶酸受体(FRα)的抗体药物偶联物(ADC),被美国食品药品监督管理局批准用于治疗FRα阳性复发性上皮性卵巢癌(EOC)患者。这一批准基于一项II期研究,该研究证明了其在此类患者中的疗效。ADC由抗体、连接子和有效载荷组成,是前所未有的新概念药物。针对OC患者的ADC的高级临床研究正在开展,以妇科癌症等实体瘤为靶点。正在进行的临床试验正在II/III期研究中评估靶向FRα、人表皮生长因子受体2、滋养层细胞表面抗原-2、钠依赖性磷酸盐转运蛋白2B和钙黏蛋白-6的ADC。在这篇综述中,我们总结了支持在OC中使用ADC的现有证据,讨论了正在进行的临床试验和临床前研究,并探讨了这些创新药物应对OC治疗挑战的潜力。