Dr Cohen on Key Trials Supporting the Use of PARP Inhibitors in Ovarian Cancer

Joshua G. Cohen, MD, FACOG, FACS, medical director, Gynecologic Cancer Program, associate clinical professor, Division of Gynecologic Oncology, Department of Surgery, City of Hope Orange County, discusses key trials supporting the use of PARP inhibitor maintenance therapy in the recurrent and up-front settings in ovarian cancer.

Advances in the field of ovarian cancer have improved the understanding of the benefits of PARP inhibition and solidified their role as frontline maintenance therapy for patients with ovarian cancer, Cohen begins.

Several trials in this space have led to changes in the indications for previously approved PARP inhibitors, which can complicate decisions about when, and in whom, to utilize these agents, he continues. However, further analysis of key phase 3 trials such as SOLO-1 (NCT01844986) and PAOLA-1 (NCT02477644) indicates that PARP inhibitors are best utilized after initial treatment for patients who have either homologous recombination deficiency (HRD) or a germline or somatic BRCA mutation, Cohen states.

The SOLO-1 trial evaluated the use of maintenance olaparib (Lynparza) vs placebo for patients with newly diagnosed advanced high-grade serous or endometrioid ovarian cancer, fallopian tube cancer, and/or primary peritoneal cancer who achieved a response with platinum-based chemotherapy. Notably, these patients also displayed BRCA1 and/or BRCA2 mutations. In a recent presentation of 7-year overall survival (OS) data, patients who received maintenance olaparib experienced a clinically meaningful survival benefit, Cohen reports. The OS rate was 67.0% in the olaparib arm vs 46.5% in the placebo arm. Although, these OS data did not reach statistical significance due to the trial’s statistical design, they do indicate long-term benefit can be seen with PARP maintenance therapy in this population.

Additionally, data from PAOLA-1 signaled potential synergy between PARP inhibitors and antiangiogenic agents, Cohen states. In this trial, the administration of maintenance olaparib plus bevacizumab (Avastin) after initial treatment provided a clear and substantial progression-free survival (PFS) benefit for patients who were HRD positive or had BRCA1/2 mutations.

Overall, both trials reinforce of the importance of identifying patients who display these features to drive PARP inhibitor selection, Cohen concludes.