Tymon-Rosario Joan, Gorman Megan, Richardson Debra L, Washington Christina, Santin Alessandro D
Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, Zucker School of Medicine at Hofstra/Northwell, Northwell Health, New Hyde Park, New York 11040.
Department of Obstetrics, Gynecology, and Reproductive Sciences Yale University School of Medicine, Connecticut 06520.
Curr Opin Obstet Gynecol. 2023 Feb 1;35(1):6-14. doi: 10.1097/GCO.0000000000000838. Epub 2022 Dec 8.
Antibody-drug conjugates (ADCs) represent a new class of drugs that combine a surface receptor-targeting antibody linked to a cytotoxic molecule delivering the potent cytotoxic payload directly to tumor cells. This review summarizes the current literature demonstrating their use in the treatment of gynecologic malignancies.
Tisotumab vedotin is the first U.S. Food and Drug Administration (FDA) approved ADC for the treatment of gynecologic cancers. While in the phase 3 randomized controlled trial in platinum resistant ovarian cancer patients, FORWARD 1, mirvetuximab did not meet its primary endpoint of progression-free survival. But we await more recent data from the two ongoing phase 3 trials of mirvetuximab in recurrent ovarian cancer patients. HER2/neu, Napi2b, mesothelin, and human trophoblast cell-surface marker (Trop-2) overexpression have also been exploited as excellent targets by novel ADCs in multiple tumors including ovarian, endometrial, and cervical cancers.
Current evidence strongly supports the use of ADCs and ongoing clinical trials will provide further information into the potential of making these drugs part of current standard practice allowing patients to be treated with a higher level of personalized cancer care.
抗体药物偶联物(ADCs)是一类新型药物,它将靶向表面受体的抗体与细胞毒性分子相连,可将强效细胞毒性药物直接递送至肿瘤细胞。本综述总结了目前证明其在妇科恶性肿瘤治疗中应用的文献。
替索单抗(Tisotumab vedotin)是首个获得美国食品药品监督管理局(FDA)批准用于治疗妇科癌症的ADC。在铂耐药卵巢癌患者的3期随机对照试验FORWARD 1中,米伐单抗(mirvetuximab)未达到无进展生存期的主要终点。但我们正在等待米伐单抗在复发性卵巢癌患者中进行的两项3期试验的最新数据。HER2/neu、Napi2b、间皮素和人滋养层细胞表面标志物(Trop-2)的过表达也已被新型ADCs用作多种肿瘤(包括卵巢癌、子宫内膜癌和宫颈癌)的优良靶点。
目前的证据有力支持了ADCs的应用,正在进行的临床试验将提供更多信息,以了解使这些药物成为当前标准治疗一部分的潜力,从而让患者能够接受更高水平的个性化癌症治疗。