FDA Grants Olaparib Priority Review for Frontline Maintenance in Ovarian Cancer

The FDA has granted a priority review designation to a supplemental new drug application (sNDA) for olaparib (Lynparza) tablets for use as a maintenance therapy in patients with newly-diagnosed, BRCA-positive advanced ovarian cancer who achieved a complete or partial response to standard frontline platinum-based chemotherapy.

The sNDA is based on data from the phase III SOLO-1 trial, in which the PARP inhibitor olaparib significantly improved progression-free survival (PFS) as frontline maintenance for this patient population. With a median follow-up of 41 months, the median PFS by independent central review was not reached in the olaparib arm (n = 260), versus 14.1 months in the placebo arm (n = 131). The investigator-assessed PFS in the olaparib arm was not reached, compared to 13.8 months in the placebo arm (HR, 0.30; 95% CI, 0.23-0.41; P <.0001).

At 36 months, the PFS rate was 60% in the olaparib group versus 27% in the placebo arm. According to AstraZeneca and Merck (MSD), the codevelopers of olaparib, the FDA action date for the sNDA is set for the first quarter of 2019.

The SOLO-1 trial (NCT01844986) evaluated maintenance olaparib following platinum-based chemotherapy in newly-diagnosed patients with advanced ovarian cancer with a BRCA1/2 mutation. Patients with newly diagnosed, FIGO stage III-IV, high-grade serous or endometrioid ovarian, primary peritoneal, or fallopian tube cancer with germline or somatic BRCA mutations were enrolled. These patients must have also received cytoreductive surgery, and be in clinical complete response or partial response after platinum-based chemotherapy.

The study treatment in SOLO-1 continued until disease progression, and treatment was ceased for patients with no evidence of disease at 2 years. Although, patients with a partial response at 2 years could continue treatment.

Secondary endpoints of the trial were PFS2, which is defined as time from randomization to second progression event, overall survival, and quality of life.

Patients who received olaparib maintenance showed a statically significant improvement in PFS2, with a median PFS2 not reached, compared with 41.9 months in the placebo group (HR, 0.50; 95% CI, 0.35-0.72; P =.0002). Overall survival data are not yet mature. Regarding quality of life, there were no clinically relevant changes. The discontinuation rate in the olaparib arm was 12%.

“It is estimated that over 50% of women on the olaparib arm were still progression free at 4 years as compared to only 11% for placebo,” Kathleen Moore, MD, principal investigator of SOLO-1, said when presented the data at the 2018 ESMO Congress.

“A key point here is that there was no change in the Kaplan-Meier curve at the 2-year mark when we stopped the olaparib or placebo therapy. So, it appears that the benefit of olaparib maintenance is extended beyond even the 2-year timepoint in which patients were receiving treatment,” added Moore, an associate professor at Stephenson Cancer Center, University of Oklahoma.

Adverse events (AEs) observed were low-grade, with the most common grade ≥3 AEs in the olaparib arm being anemia (22%) and neutropenia (8%). Baseline characteristics, including health-related quality-of-life scores, were balanced between the 2 arms.

“While ovarian cancer is a highly treatable disease due in large part to its exquisite chemosensitivity, the percentage of patients who survive disease-free for long periods of time is dismally low, and hovers in the 10% to 15% range,” said Moore. “If we are going to make meaningful improvements on that rate, it has to be with improvements in frontline treatment.”

The majority of patients with ovarian cancer recur within 3 years of diagnosis, Moore said. Although their disease has the potential to be treated, those patients are no longer considered treatable. Moore emphasized the importance of SOLO-1, as it is the first phase III large prospective data set for this population of women.

Olaparib is currently FDA approved for the maintenance treatment of recurrent ovarian cancer in response to platinum-based chemotherapy regardless of BRCA mutation status, and for the treatment of advanced ovarian cancer patients with a germline BRCA mutation previously treated with 3 or more lines of chemotherapy.

Moore K, Colombo N, Scambia G, et al. Olaparib maintenance therapy following first-line platinum-based chemotherapy in patients with FIGO stage III—IV ovarian cancer (OC) with a BRCA1/2 mutation (BRCAm): Phase III SOLO1 trial. In: Proceedings from the 2018 ESMO Congress; October 19-23, 2018; Munich, Germany. Abstract LBA7_PR