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

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.