Dr Zeybek on the Investigation of Neoadjuvant Olaparib in Newly Diagnosed BRCA-Mutant Ovarian Cancer

Burak Zeybek, MD, clinical assistant professor, department of obstetrics and gynecology, University of Florida College of Medicine, discusses key results and clinical implications from the phase 1 NOW trial (NCT03943173) investigating neoadjuvant olaparib (Lynparza) plus adjuvant chemotherapy in patients with newly diagnosed, BRCA-mutant ovarian cancer.

Research on the use of PARP inhibitors as a frontline treatment within gynecologic oncology has steadily increased over the past 5 years, which is demonstrated in the the single-arm, open-label, NOW study, Zeybek says. The phase 1 trial evaluated the the feasibility of neoadjuvant treatment with olaparib prior to surgical resection in patients with advanced, high-grade, BRCA-mutant ovarian, primary peritoneal, or fallopian tube cancer. Feasibility was defined by a patient's level of unacceptable toxicity or disease progression.

Patients were treated with 2 cycles of neoadjuvant olaparib prior to undergoing cytoreductive surgery, Zeybek continues. Those who experienced disease progression or responses not amenable to surgery were then treated with a median number of 6 cycles of paclitaxel or carboplatin in the adjuvant setting. Conversely, patients who had a response with olaparib underwent surgery, followed by adjuvant chemotherapy and PARP inhibitor maintenance according to the investigator's discretion.

Olaparib was found to successfully reduce tumor volume, which allowed more patients to proceed to surgery without the need for chemotherapy, Zeybek states. Of these 14 patients that underwent cytoreductive surgery, 85.7% had no gross residual disease. Moreover, 93% of patients had a 25% reduction in CA-125 levels, which indicates the regimen's success in reducing tumor burden, Zeybek adds.

Although results from this study are encouraging, it is important to acknowledge that this is a pilot study with a smaller study population, Zeybek notes. Based on these findings, a larger follow-up study of neoadjuvant olaparib is likely to occur in this patient population, Zeybek concludes.