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 

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 

 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 

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

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Joshua G. Cohen, MD, FACOG, FACS, discusses key trials supporting the use of PARP inhibitor maintenance therapy in upfront setting in ovarian cancer.

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

Joshua G. Cohen, MD, FACOG, FACS, an assistant professor in the Division of Gynecologic Oncology at University of California, Los Angeles (UCLA) and gynecologic oncologist at Ronald Reagan UCLA Medical Center, discusses the efficacy of PARP inhibitors in patients with ovarian cancer.

When looking at recent clinical trials that have read out in ovarian cancer, the hazard ratios have been very impressive with some of the targeted agents analyzed, Cohen says. These agents have been particularly beneficial in patients with somatic or germline 

 mutations. In these subgroup, a median progression-free survival (PFS) benefit of 12 months to 24 months has been reported. Such a benefit has been unheard of in the current treatment paradigm comprised of platinum-based chemotherapy, according to Cohen.

In the phase 3 ENGOT-OV16/NOVA study, which examined the efficacy of niraparib (Zejula) maintenance therapy in patients with platinum-sensitive, recurrent ovarian cancer, patients who had a 

 mutation experienced a median PFS of 21 months compared with 5.5 months in those who did not receive a maintenance PARP inhibitor, concludes Cohen.

Joshua G. Cohen, MD, FACOG, FACS, discusses the efficacy of PARP inhibitors in patients with ovarian cancer.

Dr. Cohen on the Efficacy of PARP Inhibitors in Ovarian Cancer

Joshua G. Cohen, MD, assistant professor, Division of Gynecologic Oncology, University of California, Los Angeles, discusses surgery in patients with early-stage ovarian cancer.

There are varying subtypes of ovarian cancer, both histologically and molecularly, that imply differing courses of treatment, says Cohen. Many women with early-stage ovarian cancer do not need to undergo chemotherapy. These women have had their lymph nodes tested, and have undergone surgical biopsies to make sure that the cancer has not spread, explains Cohen.

Based on that, physicians can focus on fertility management, as many patients with early-stage ovarian cancer are younger. It gives these patients a unique opportunity to maintain their hormonal function, as well as possibly have children in the future.

There has been some controversy surrounding the idea of minimally-invasive surgery for early-stage ovarian cancer, Cohen says. Additionally, there is a new staging system, which some believe may impact how patients with ovarian cancer are managed.

Dr. Cohen Discusses Surgery in Early-Stage Ovarian Cancer

Joshua G. Cohen, MD, assistant professor, Division of Gynecologic Oncology, University of California, Los Angeles, discusses the evolution of surgery in the treatment of patients with ovarian cancer.

If a woman was diagnosed with ovarian cancer 20 years ago, the standard of care at any age would have been to remove the uterus, the fallopian tubes, and the ovaries—essentially putting a woman into surgical menopause, says Cohen. Physicians now know that that is not necessary.

For women who have disease that is confined to 1 ovary or 1 fallopian tube, surgeons can oftentimes only remove the diseased or affected area and use a biopsy to check the lymph nodes and other ovary if it looks concerning. Surgeons do their best to leave those structures in place if a patient is young and it makes sense based on the spread of disease and histologic grade.

This has enabled surgeons to move away from a 1 treatment fits all approach to a more tailored approach based on age and reproductive wishes, states Cohen.

Joshua G. Cohen, MD, FACOG, FACS

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