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Maintenance therapy with niraparib significantly improved progression-free survival compared with placebo in Chinese patients with newly diagnosed advanced ovarian cancer who achieved a complete response or partial response to first-line chemotherapy.
Maintenance therapy with niraparib (Zejula) significantly improved progression-free survival (PFS) compared with placebo in Chinese patients with newly diagnosed advanced ovarian cancer who achieved a complete response (CR) or partial response (PR) to first-line chemotherapy, according to data from the phase 3 PRIME trial (NCT03709316).1
Among patients who achieved a CR to frontline chemotherapy, those treated with niraparib (n = 212) achieved a median PFS of 29.4 months (95% CI, 19.3–not estimable [NE]) compared with 8.3 months (95% CI, 7.3-12.0) with placebo (n = 103; HR, 0.45; 95% CI, 0.32-0.61; P < .001). In the subgroup of patients who experienced a partial response to chemotherapy, those who were treated with maintenance niraparib (n = 43) had a median PFS of 19.3 months (95% CI, 11.1-NE), vs 8.3 months (95% CI, 5.6-11.1) with placebo (n = 26; HR, 0.45; 95% CI, 0.23-0.86; P = .014).
Notably, those who were treated with niraparib and achieved a CR to first-line chemotherapy experienced a numerically longer PFS than those who experienced a PR (HR, 0.67; 95% CI, 0.43-1.05).
“In [patients treated with] niraparib, those with a CR achieved numerically longer median PFS than those with a PR, which warrants further investigation in a larger study given the small sample size of the PR subgroup,” Rutie Yin, lead study author, member of the Department of Gynecology and Obstetrics, and the Key Laboratory of Obstetrics and Gynecologic and Pediatric Diseases and Birth Defects of the Ministry of Education at the West China Second University Hospital at Sichuan University, and colleagues, wrote in a poster of the data presented during the 2022 ASCO Annual Meeting.
Although platinum-based chemotherapy generates responses in patients with advanced ovarian cancer, approximately 75% of patients with advanced disease will relapse within 18 to 24 months of treatment. In April 2020, the FDA approved niraparib for the maintenance treatment of adult patients with advanced epithelial ovarian, fallopian tube, or primary peritoneal cancer who are in a CR or PR to frontline platinum-based chemotherapy, regardless of biomarker status.2 A few months later, in September 2020, the China National Medical Products Administration approved niraparib for the same indication.3
The PRIME trial was designed to further evaluate the PARP inhibitor in newly diagnosed patients with advanced ovarian cancer who achieved a response following first-line chemotherapy. The trial enrolled patients who were at least 18 years of age with FIGO stage III/IV ovarian cancer who had a high-grade serous or endometroid tumor. Other key inclusion criteria included receiving prior primary or interval cytoreductive surgery and a CR or PR to first-line platinum–based chemotherapy.
Once enrolled, patients were randomized 2:1 to receive 200 mg of oral niraparib or placebo once daily. Those with a body weight of at least 77 kg and a platelet count of at least 150,000 µL were given 300 mg of niraparib or placebo once daily.
Stratification factors included the presence of germline BRCA mutations (yes vs no), homologous recombination deficiency status (positive vs negative), prior neoadjuvant chemotherapy (yes vs no), and response to first-line chemotherapy (CR vs PR).
PFS per blinded independent central review in the intention-to-treat (ITT) population served as the primary end point of the trial. Secondary end points included overall survival (OS) and time to next treatment in the ITT population, PFS and OS in the HRD subgroup, and safety.
Prior data presented at the 2022 SGO Annual Meeting on Women’s Cancer showed that in the ITT population, treatment with maintenance niraparib resulted a median PFS of 24.8 months (95% CI, 19.2-NE) compared with 8.3 months (95% CI, 7.3-11.1) in the placebo arm (HR, 0.45; 95% CI, 0.34-0.60; P < .001).4 Data presented during the 2022 ASCO Annual Meeting further explored the safety and efficacy of niraparib in patients based on their responses to first-line chemotherapy.
Baseline characteristics were comparable across the 4 subgroups of responders. Most patients in each subgroup had FIGO stage III disease, did not receive neoadjuvant chemotherapy, did not have germline BRCA mutations, and had optimal residual disease (R0 and R1) following surgery.
Regarding safety, the toxicity profile of niraparib was consistent with what has been reported in prior clinical trials, with no new safety signals revealed.
The rates of any treatment-emergent adverse effects (TEAEs) in the complete responders who received niraparib, complete responders who received placebo, partial responders given niraparib, and partial responders administered placebo were 99.1%, 92.2%, 100%, and 100%, respectively. In the niraparib-treated CR subset and niraparib-treated PR subset, TEAEs leading to dose interruption occurred in 60.8% and 72.1% of patients, respectively. TEAEs resulting in dose reduction occurred in 37.7% and 53.5% of patients, respectively. TEAEs led to treatment discontinuation in 5.7% and 11.6% of patients, respectively.
In the CR and PR niraparib-treated subgroups, the rates of grade 3 or higher TEAEs were 54.2% and 55.8%, respectively. The most common grade 3 or higher TEAEs were anemia (18.9% and 14%), decreased neutrophil count (18.9% and 11.6%), decreased platelet count (12.3% and 23.3%), and decreased white blood cell count (7.1% and 4.7%).