The evolving landscape of antibody-drug conjugates in gynecologic cancers

Despite significant advances in the treatment of cervical, ovarian, and uterine cancers with the approvals of checkpoint and PARP inhibitors into standard treatment, patients with recurrent metastatic gynecologic malignancies still experience poor outcomes, and most of these patients will experience disease relapse. Once standard preferred treatments are exhausted, options have historically been limited to treatments associated with poor outcomes and notable toxicities. Consequently, novel therapies that are effective and well-tolerated are needed for patients with recurrent and metastatic gynecologic malignancies. Antibody-drug conjugates (ADCs) are a class of targeted therapies that are well established in several cancers including hematologic malignancies and some solid tumors. Significant strides in ADC technology and design have led to improvements in efficacy and safety with newer-generation ADCs. Consequently, ADCs are gaining traction in gynecologic cancers with the recent US Food and Drug Administration approvals of tisotumab vedotin in cervical cancer and mirvetuximab soravtansine in ovarian cancer. Many additional ADCs against various targets are being explored in patients with metastatic or recurrent gynecologic malignancies. The purpose of this review is to summarize the nuanced structural and functional properties of ADCs, while outlining opportunities for innovation. Further, we highlight the ADCs in clinical development for gynecologic malignancies, exploring how ADCs may be able to address the clinical care gap for patients with gynecologic cancers.