Current Systemic Treatment Landscape of Advanced Gynecologic Malignancies

Developments in systemic therapies beyond traditional cytotoxic chemotherapy have resulted in an unparalleled number of US Food and Drug Administration approvals in the past 5 years for ovarian, endometrial, and cervical cancer. In this review, we highlight registration trials leading to recent Food and Drug Administration approvals for targeted systemic therapies in advanced gynecologic malignancies, encompassing three classes of agents: the antiangiogenic anti-vascular endothelial growth factor antibody bevacizumab in ovarian and cervical cancer, poly (ADP-ribose) polymerase inhibitors in ovarian cancer, and the immune checkpoint inhibitor pembrolizumab in cervical and endometrial cancer. The addition of bevacizumab to chemotherapy has been approved in frontline and relapsed advanced ovarian cancer, in both platinum-resistant and platinum-sensitive settings. Three poly (ADP-ribose) polymerase inhibitors are approved for women with ovarian cancer. Olaparib and rucaparib are utilized in recurrent germline or somatic BRCA mutated ovarian cancer. Along with a third poly (ADP-ribose) polymerase inhibitor, niraparib, they are also Food and Drug Administration approved as maintenance therapy regardless of BRCA mutation status for patients with recurrent ovarian cancer in complete or partial response to platinum-based chemotherapy. More recently, olaparib was approved as maintenance therapy for BRCA mutated ovarian cancer following first-line platinum-based chemotherapy. Pembrolizumab has been approved for relapsed cervical cancer with programmed death ligand 1 positivity and relapsed solid tumors with mismatch repair deficiency, which applies to 30% of endometrial cancers. Together, these therapies represent the advent of personalized medicine in gynecologic malignancies. Additional information is required to determine cost-effective strategies for incorporating these therapies and rational means of sequencing these agents.