China’s National Medical Products Administration has granted marketing authorization for olaparib as a first-line maintenance treatment for adult patients with newly diagnosed advanced germline or somatic BRCA-mutated epithelial ovarian, fallopian tube, or primary peritoneal cancer who are in complete or partial response to frontline platinum-based chemotherapy.
China’s National Medical Products Administration has granted marketing authorization for olaparib (Lynparza) as a first-line maintenance treatment for adult patients with newly diagnosed advanced germline or somatic BRCA-mutated epithelial ovarian, fallopian tube, or primary peritoneal cancer who are in complete or partial response (PR) to frontline platinum-based chemotherapy.1
The approval is based on findings from the phase III SOLO-1 trial, in which the PARP inhibitor led to a 70% reduction in the risk of disease progression or death compared with placebo in this patient population (HR, 0.30; 95% CI, 0.23-0.41; P <.001).2,3 The 3-year progression-free survival (PFS) rates were 60% and 27% for those who received olaparib and placebo, respectively.
“This approval marks a new era for women with BRCA-mutated advanced ovarian cancer in China, where the prevalence of BRCA mutations in advanced disease is higher than the international average,” Dave Fredrickson, executive vice president, oncology business unit, AstraZeneca, which co-develops olaparib with Merck (MSD), stated in a press release. “Currently, 70% of women relapse within three years of initial treatment, representing the highest reoccurrence rate among gynecological cancers worldwide. The progression-free survival benefit of Lynparza observed in SOLO-1 is a significant step towards helping these women achieve long-term remission.”
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 had 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.
At a median follow-up of 41 months, results showed that 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.
The FDA and European Commission approved olaparib for this indication in December 2018 and June 2019, respectively, also based on the phase III SOLO-1 findings. Olaparib is also approved in 38 countries, including the United States, countries in the European Union and Japan, for germline BRCA-mutant HER2-negative metastatic breast cancer who were previously treated with chemotherapy; this includes locally advanced breast cancer in the European Union.
Recently, results of the phase III PAOLA-1 trial showcased a benefit with olaparib in combination as a frontline maintenance regimen. Specifically, olaparib combined with bevacizumab (Avastin) improved median PFS by 5.5 months compared with bevacizumab and placebo for patients with newly diagnosed, advanced ovarian cancer who were in complete or partial response to first-line therapy with bevacizumab and platinum-based chemotherapy. The benefit was observed regardless of BRCA status, but was more pronounced for patients with tumors testing positive for BRCA1/2 mutations and for those with a homologous recombination deficiency (HRD) score of ≥42 by the myChoice HRD Plus assay.4