Dr Barroilhet on the Role of PARP Inhibitors in BRCA+ and HRD Ovarian Cancer

Lisa Barroilhet, MD, associate professor, Department of Obstetrics and Gynecology, University of Wisconsin (UW) School of Medicine and Public Health; gynecologic oncologist, UW Health, discusses the role of PARP inhibitors in patients with ovarian cancer.

All patients with ovarian cancer displaying somatic or germline BRCA mutations should receive upfront PARP inhibitor maintenance therapy after completing an initial 6 cycles of chemotherapy with paclitaxel and carboplatin, Barroilhet says. Patients can receive PARP maintenance as neoadjuvant therapy or as adjuvant therapy following debulking surgery, Barroilhet notes.

Findings from the phase 3 SOLO1 trial (NCT01844986) support the use of maintenance olaparib (Lynparza) in patients with BRCA-mutated ovarian cancer, Barroilhet explains. In this trial, patients with newly diagnosed advanced ovarian cancer harboring a BRCA1/2 mutation and experiencing a clinical response to platinum-based chemotherapy were randomly assigned to receive either maintenance olaparib or placebo for a maximum of 2 years. At a median follow-up of 7 years, the overall survival rates were 67.0% in the olaparib arm vs 46.5% in the placebo arm (HR, 0.55; 95% CI, 0.40-0.76; P = .0004).

Patients with ovarian cancer with homologous recombination deficiency (HRD) may also benefit from PARP maintenance therapy, according to Barroilhet. If a patient’s germline test comes back normal, their biopsy should be sent for HRD testing to inform further treatment decisions, Barroilhet says.

In the phase 3 PRIMA trial (NCT02655016), patients with newly diagnosed advanced ovarian cancer were randomly assigned to receive either niraparib (Zejula) or placebo after response to platinum-based chemotherapy. Of the enrolled patients, 50.9% had HRD tumors. In the HRD population, the median progression-free survival (PFS) was 21.9 months with niraparib vs 10.4 months with placebo (HR, 0.43; 95% CI, 0.31-0.59; P < .001). In the overall population, the median PFS was 13.8 months with niraparib vs 8.2 months with placebo (HR, 0.62; 95% CI, 0.50-0.76; P < .001). Based on these data, and with shared decision making, niraparib maintenance therapy can be considered for patients with HRD disease, Barroilhet explains.

Patients treated with bevacizumab (Avastin) plus upfront or neoadjuvant chemotherapy can continue to receive a dual maintenance approach with bevacizumab plus olaparib, Barroilhet notes. This combination may be effective in patients with HRD ovarian cancer, Barroilhet concludes.