Japan’s Pharmaceuticals and Medical Devices Agency approved olaparib as a maintenance treatment for patients with BRCA-mutant ovarian cancer after undergoing first-line chemotherapy.
Japan’s Pharmaceuticals and Medical Devices Agency (PMDA) approved olaparib (Lynparza) as a maintenance treatment for patients with BRCA-mutant ovarian cancer after undergoing first-line chemotherapy.
The approval was based on findings from the randomized, double-blinded, phase III SOLO-1 study, in which maintenance olaparib significantly improved progression-free survival (PFS) compared with placebo in this patient population following frontline platinum-based chemotherapy.
Olaparib is the sole PARP inhibitor that is approved for use in Japan.
“This approval in Japan is a critical advance for women with ovarian cancer and a BRCA mutation,” Dave Fredrickson, executive vice-president, oncology, AstraZeneca, which co-develops olaparib with Merck, stated in a press release. “The goals of frontline therapy are long-term remission or a cure, yet currently 70% of patients relapse within 3 years of initial treatment. The progression-free survival benefit of Lynparza observed in SOLO-1 represents a major step forward in our ambition to improve patient outcomes.”
The Japanese approval follows the European Commission’s June 2019 decision to approve single-agent olaparib for the maintenance treatment of adult patients with advanced BRCA1/2-mutated germline and/or somatic high-grade epithelial ovarian, fallopian tube, or primary peritoneal cancer who are in complete or partial response (PR) following first-line platinum-based chemotherapy. The FDA approved olaparib in this setting in December 2018.
In the phase III SOLO-1 trial, maintenance olaparib following platinum-based chemotherapy was evaluated 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. The patients must have also undergone cytoreductive surgery, and be in clinical complete response or PR following platinum-based chemotherapy.
Treatment was continued until disease progression, and was ceased for patients with no evidence of disease at 2 years. However, patients with a PR at 2 years could continue therapy.
The primary endpoint was PFS, and secondary endpoints of the trial were PFS2—which is defined as time from randomization to second progression event—overall survival, and quality of life.
Results showed that, at a median follow-up of 41 months, maintenance olaparib led to a 70% reduction in the risk of disease progression or death versus placebo (HR, 0.30; 95% CI, 0.23-0.41; P <.001).2,3 Moreover, 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 with 13.8 months in the placebo arm.
Additionally, 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. There were no clinically relevant changes in quality of life (QoL). Moreover, the discontinuation rate in the olaparib arm was 12%.
Regarding safety, adverse events 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.
Additional studies are evaluating olaparib in other settings and in combination regimens. For example, the ongoing phase III PAOLA-1 study, is testing the combination of olaparib and bevacizumab (Avastin) as a first-line maintenance treatment for patients with advanced, stage IIIB-IV high-grade serous or endometrioid, fallopian tube, or peritoneal ovarian cancer, regardless of BRCA status.