The FDA has granted a priority review designation to a supplemental new drug application (sNDA) for Lynparza (olaparib) 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.
BY Jason M. Broderick and Angelica Welch
The FDA has granted a priority review designation to a supplemental new drug application (sNDA) for Lynparza (olaparib) 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 3 SOLO-1 trial, in which the PARP inhibitor Lynparza 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 Lynparza arm (260 patients), versus 14.1 months in the placebo arm (131 patients). The investigator-assessed PFS in the Lynparza arm was not reached, compared to 13.8 months in the placebo arm.
At 36 months, the PFS rate was 60 percent in the Lynparza group versus 27 percent in the placebo arm. According to AstraZeneca and Merck (MSD), the codevelopers of Lynparza, the FDA action date for the sNDA is set for the first quarter of 2019.
The SOLO-1 trial (NCT01844986
) evaluated maintenance Lynparza following platinum-based chemotherapy in newly-diagnosed patients with advanced ovarian cancer with a BRCA1/2
mutation. Patients with newly diagnosed, FIGO stage 3-4, 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 two years. Although, patients with a partial response at two 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 Lynparza maintenance showed a statically significant improvement in PFS2, with a median PFS2 not reached, compared with 41.9 months in the placebo group. Overall survival data are not yet mature. Regarding quality of life, there were no clinically relevant changes. The discontinuation rate in the Lynparza arm was 12 percent.
“It is estimated that over 50 percent of women on the olaparib arm were still progression free at four years as compared to only 11 percent for placebo,” Kathleen Moore, M.D., 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 two-year mark when we stopped the olaparib or placebo therapy. So, it appears that the benefit of olaparib maintenance is extended beyond even the two-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 or higher AEs in the Lynparza arm being anemia (22 percent) and neutropenia (8 percent). Baseline characteristics, including health-related quality-of-life scores, were balanced between the two 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 percent to 15 percent 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 three 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 3 large prospective data set for this population of women.
Lynparza 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 three or more lines of chemotherapy.
A version of this article originally appeared on OncLive.com under the title, "FDA Grants Olaparib Priority Review for Frontline Maintenance in Ovarian Cancer."