Advancing antibody-drug conjugates in gynecological malignancies: myth or reality?

Abstract

Antibody-drug conjugates (ADCs) represent a new class of therapeutic agents designed to target specific antigens on tumor cells, combining the specificity of monoclonal antibodies to the cytotoxicity of classic chemotherapy agents. These drugs have been extensively studied both in solid and hematologic malignancies, leading to substantial improvement in the therapeutic landscape for several tumors. Despite no ADC have been yet approved for the treatment of gynecological malignancies, some agents have shown promising results and might have the potential to become part of the standard of care. Among them, mirvetuximab soravtansine has shown activity in platinum-resistant ovarian cancer with high folate-α receptor expression, as a single agent and in combination. Tisotumab vedotin is active in patients with pre-treated cervical cancer, and further investigation is ongoing. The purpose of this review is to summarize the structural and functional characteristics of ADCs and analyze the most recent and promising data regarding the clinical development of ADCs in gynecological malignancies. The available data on the efficacy of the more studied ADCs in ovarian, endometrial, and cervical cancers will be discussed along with toxicities of special interest, the mechanisms of resistance, and future possible drugs combination.

Mirvetuximab Soravtansine in Solid Tumors: A Systematic Review and Meta-Analysis

“…The ideal mechanism relies on cellular receptor internalization to deliver the cytotoxic agent directly to the tumor cells. (Nerone, Grande et al 2022) ADCs have gained ground in treating solid tumors with the FDA approval of trastuzumab emtansine (T-DM1) in February 2013 for metastatic and early-stage breast cancer. (Boyraz, Sendur et al 2013) Mirvetuximab Soravtansine (MIRV) is also one of the recently FDA-accelerated ADCs that is used to treat solid tumors.…”

“…(Burton, Bottino et al 2019) Based on the advantages mentioned above, the application prospects of MIRV in solid tumors expressing FRα are very promising. Although it has received accelerated approval from the FDA, there remains an urgent need to evaluate its e cacy, safety, and other aspects (Nerone, Grande et al 2022). In particular, the e cacy and safety of combining MIRV with chemotherapy or other targeted agents, including immunotherapy, need to be further analysed.…”