Maintenance Treatment of Newly Diagnosed Advanced Ovarian Cancer: Time for a Paradigm Shift?

SIMPLE SUMMARY: Advanced epithelial ovarian cancer has a poor prognosis, but targeted therapies have been developed and are providing new hope. We reviewed recent results with PARP inhibitors as treatment and/or maintenance therapy following chemotherapy in newly diagnosed advanced ovarian cancer. Data confirm the benefit of PARP inhibitors in this setting, especially in subgroups with genomic instability. We describe the implications of these trial results for clinical practice, focusing on the need for a personalized treatment approach based on biomarker profile and other factors, including tolerability, cost considerations, and physician and patient preference. We have developed a systemic treatment algorithm for newly diagnosed advanced ovarian cancer, intended as a tool for clinicians to aid decision making in their daily practice. We also consider areas of future research, such as exploring further options for patients whose disease relapses following PARP inhibitor treatment. ABSTRACT: Recent data have demonstrated substantial efficacy with poly (ADP-ribose) polymerase (PARP) inhibitors as treatment and/or maintenance therapy in patients with newly diagnosed advanced epithelial ovarian cancer (EOC). Here, we review efficacy and safety results from four recent Phase III trials in newly diagnosed EOC: SOLO1 (olaparib), PAOLA-1 (olaparib in combination with bevacizumab), PRIMA (niraparib), and VELIA (veliparib). The implications of these data for current clinical practice and areas for future research are discussed, including ongoing studies of targeted agents in the newly diagnosed setting. Data from SOLO1, PAOLA-1, PRIMA, and VELIA confirm the benefit of PARP inhibitors (olaparib, niraparib, veliparib) for women with newly diagnosed EOC. The greatest benefit was seen in patients with a BRCA1 and/or BRCA2 mutation or in the homologous recombination deficiency (HRD)-test positive subgroup. These four well-conducted studies have generated practice-changing data. However, deciding how to apply these results in clinical practice is challenging, and substantial differences in trial design impede cross-trial comparisons. Recent PARP inhibitor approvals (olaparib, niraparib) in the newly diagnosed EOC setting have provided new maintenance treatment options for a broader patient population. The results of these studies call for personalized medicine based on biomarker profile and other factors, including tolerability, cost considerations, and physician and patient preference. Important areas for future research include appropriate use of both BRCA mutation and HRD testing to inform magnitude of PARP inhibitor benefit as well as exploring further options for patients who are HRD-test negative and for those who become PARP inhibitor resistant.