Ovarian Cancer Therapy

Significant advances in basic and translational research have improved our understanding of the molecular alterations and biological vulnerabilities of the different histologic subsets of epithelial ovarian cancer (EOC). This has led to clinical trials that have incorporated novel agents based on molecular aspects into the treatment paradigm for both newly diagnosed and recurrent disease. The past decade has witnessed several regulatory approvals in the United States and Europe for the treatment of EOC, including the antiangiogenic agent, bevacizumab, poly(ADP-ribose) polymerase inhibitors in various therapeutic settings, and the antibody-drug conjugate (ADC), mirvetuximab soravtansine. Immune checkpoint inhibitors do not demonstrate substantial activity as single agents in ovarian cancer, except for the rare entity of microsatellite instability (MSI) high ovarian cancer. Current research is focused on new treatment paradigms such as ADCs, genetically specific therapies, and other novel immunotherapies such as bispecific antibodies, radioligand therapies, cellular therapies, and vaccines. In addition, combination efforts are focused on incorporating conventional chemotherapy, targeted therapies, immune-oncology drugs, and/or novel agents to improve outcomes for patients with newly diagnosed as well as recurrent EOC. This review will focus on the management of high-grade serous ovarian cancer, the most common type of EOC, accounting for ∼75% of cases. Recent advances in the management of rarer histologic subtypes with distinct molecular and clinical characteristics, including clear cell, mucinous, endometrioid, and low-grade serous, will be briefly discussed. Non-EOCs, including germ cell and sex cord stromal tumors and their treatment, have been reviewed elsewhere [see Ray-Coquard et al. (2019) <i>N Engl J Med</i> <b>381:</b> 2416-2428. doi:10.1056/NEJMoa1911361].