Maintenance therapy in gynecologic malignancies: Current and future state

Although there have been significant advances in the management of gynecologic malignancies in recent years, individuals with advanced disease continue to have high rates of recurrence. Strategies to decrease rates of recurrence and increase time to recurrence are urgently needed. Historically, prolonged chemotherapy treatment and consolidation therapy were unsuccessful. However, continuation of maintenance therapy after initial chemotherapy may offer improved progression-free survival (PFS) and overall survival (OS) in select circumstances. In recent years, maintenance agents including VEGF and poly(adenosine diphosphate ribose) polymerase (PARP) inhibitors have improved PFS and sometimes even OS among women with ovarian cancer when used as monotherapy or in combination. PARP inhibitors demonstrate particularly robust results in patients with BRCA-mutated disease or other homologous recombination-deficient cancers. In endometrial and cervical cancers, immune checkpoint inhibitors combined with chemotherapy and used as maintenance thereafter have improved PFS and OS, with particular benefits noted in mismatch repair-deficient endometrial cancer and PD-L1-positive cervical cancer. Beyond currently available therapies, ongoing trials are exploring additional options for maintenance therapy, including antibody-drug conjugates, hormone-directed therapies, and novel targeted therapies such as XPO-1 inhibitors. Maintenance therapy can be accompanied by increased toxicity and cost; as such, careful consideration must be made about the relative benefit of any given maintenance strategy weighed against potential impacts on quality of life or financial toxicity. This review focuses on current maintenance therapy practices, emerging areas of research, and challenges in this area of study.