Dr. Brown on the Use of PARP Inhibitors in the Upfront and Recurrent Settings in Ovarian Cancer

Jubilee Brown, MD, professor, director, gynecologic oncology, Levine Cancer Institute, Atrium Health, discusses benefits associated with PARP inhibitor maintenance therapy in the upfront and recurrent settings of ovarian cancer.

Previous research has demonstrated that PARP inhibitor maintenance provides clinical benefit to patients with BRCA or BRCA-related mutations in the germline or somatic settings, Brown begins. Moreover, all patients will experience some degree of benefit regardless of whether they have homologous recombination deficiency (HRD), Brown adds. 

With mature data reporting out from several key trials in ovarian cancer, the use of PARP inhibitor maintenance therapy in ovarian cancer has gained support, Brown states. For example, the phase 3 PAOLA-1 study (NCT02477644) evaluated the addition of olaparib (Lynparza) to bevacizumab (Avastin) maintenance therapy vs placebo after first-line platinum-based chemotherapy in patients with newly diagnosed, advanced ovarian cancer, Brown details. The trial's primary end point was progression-free survival (PFS). 

Primary analysis of the trial showed that olaparib and bevacizumab maintenance led to a significant increase in PFS vs placebo, Brown says. This benefit was specifically observed in patients with HRD, she adds. In the final overall survival (OS) analysis of this trial, patients who were HRD-positive had a 5-year OS rate of 65.5% with the experimental regimen. Conversely, patients without HRD did not experience OS benefit.

There is no comparison of patient outcomes with a PARP inhibitor combination regimen vs PARP monotherapy in this population, Brown notes. Despite this limitation, the trial confirms the efficacy of PARP inhibitor maintenance therapy in the upfront setting and indicates that this option should be offered to patients as a standard of care, she emphasizes.

Although the use of PARP inhibitor maintenance therapy in the first line appears confirmed, newer data in the recurrent setting has led clinicians to decrease their use in certain scenarios, Brown says. More research is needed to determine the best use of PARP inhibitors in this space, Brown concludes.

Editor's Note: Dr Brown reports former Speakers’ Bureau involvement with Clovis and Eisai; advisory board positions with Caris, Biodesix, Janssen, Tempus, AstraZeneca, Tesaro/GSK, and Clovis; consulting/speaking positions with Olympus, Clovis, Invitae, and Caris; and research positions with Tesaro/GSK and Genentech.