Clinical applications of antibody drug conjugates for gynecologic malignancies: Review of available medicines and emerging therapeutics

IF 4.5 2区 医学 Q1 OBSTETRICS & GYNECOLOGY
Alyssa C. Bujnak , Samantha A. Solaru , Krishnansu Tewari
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引用次数: 0

Abstract

With significant overall survival benefits reported in several phase 3 randomized clinical trials, the integration of anti-PD-1 immunotherapy with systemic chemotherapy has transformed the therapeutic landscape in advanced endometrial cancer and PD-L1+ recurrent/metastatic cervical cancer. For patients with FIGO stage III-IVA locally advanced cervical cancer, irrespective of PD-L1 status, chemoradiation plus pembrolizumab followed by maintenance pembrolizumab also confers a survival benefit. For newly diagnosed advanced ovarian cancer responding to primary systemic chemotherapy, maintenance therapy using PARP inhibitors and/or bevacizumab according to germline and somatic mutational analysis have been demonstrated to improve progression-free survival. Tumor heterogeneity, acquired drug resistance, and adverse events limit long-term effectiveness. Antibody-drug conjugates (ADCs) represent an innovative new class of medicines with activity in gynecologic malignancies and distinct toxicity profiles attributable to ADC construction. Adverse event mitigation strategies, biomarker discovery, and sequencing are paramount in successfully exploiting the therapeutic window provided by these novel compounds. This review discusses the application of ADCs in gynecologic cancers, including the current FDA-approved drugs mirvetuximab soravtansine, tisotumab vedotin, and trastuzumab deruxtecan, as well as relevant ongoing clinical trials, including TROP2 ADCs.
抗体药物偶联物在妇科恶性肿瘤中的临床应用:现有药物和新兴治疗方法综述
几个3期随机临床试验报告了显著的总体生存期,抗pd -1免疫治疗与全身化疗的结合已经改变了晚期子宫内膜癌和PD-L1+复发/转移性宫颈癌的治疗前景。对于FIGO III-IVA期局部晚期宫颈癌患者,无论PD-L1状态如何,放化疗加派姆单抗再加维持派姆单抗也能带来生存获益。对于对原发性全身化疗有反应的新诊断的晚期卵巢癌,根据种系和体细胞突变分析,使用PARP抑制剂和/或贝伐单抗进行维持治疗已被证明可以改善无进展生存期。肿瘤异质性、获得性耐药和不良事件限制了长期疗效。抗体-药物偶联物(ADC)是一类创新的新型药物,在妇科恶性肿瘤中具有活性,并且由于ADC结构而具有独特的毒性。不良事件缓解策略、生物标志物的发现和测序对于成功利用这些新化合物提供的治疗窗口至关重要。本综述讨论了adc在妇科癌症中的应用,包括目前fda批准的药物mirvetuximab soravtansine, tisotumab vedotin和曲妥珠单抗deruxtecan,以及相关的正在进行的临床试验,包括TROP2 adc。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
Gynecologic oncology
Gynecologic oncology 医学-妇产科学
CiteScore
8.60
自引率
6.40%
发文量
1062
审稿时长
37 days
期刊介绍: Gynecologic Oncology, an international journal, is devoted to the publication of clinical and investigative articles that concern tumors of the female reproductive tract. Investigations relating to the etiology, diagnosis, and treatment of female cancers, as well as research from any of the disciplines related to this field of interest, are published. Research Areas Include: • Cell and molecular biology • Chemotherapy • Cytology • Endocrinology • Epidemiology • Genetics • Gynecologic surgery • Immunology • Pathology • Radiotherapy
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