Frontline niraparib in addition to bevacizumab as maintenance demonstrated impressive clinical activity in patients with advanced ovarian cancer who achieved either a complete or partial response to frontline platinum-based chemotherapy with bevacizumab, according to the phase II OVARIO trial.
Frontline niraparib (Zejula) in addition to bevacizumab (Avastin) as maintenance demonstrated impressive clinical activity in patients with advanced ovarian cancer who achieved either a complete or partial response (PR) to frontline platinum-based chemotherapy with bevacizumab, according to the phase II OVARIO trial (NCT03326193).
Results from the interim analysis, which were made available as part of the virtual platform for the SGO 2020 Annual Meeting, demonstrated that the 6-month progression-free survival (PFS) rate was 89.5% in patients who received the combination of the PARP inhibitor and the VEGF-directed agent.
In the single-arm study, investigators evaluated the combination of niraparib and bevacizumab in 105 patients with advanced ovarian cancer who responded to frontline platinum-based chemotherapy combined with bevacizumab. Bevacizumab was administered at 15 mg/kg every 3 weeks ≤15 months, including the time on frontline chemotherapy, and niraparib was given at 200 mg or 300 mg once daily, and was started within 12 weeks of completing frontline therapy. Treatment continued for 3 years, or until progressive disease or unacceptable toxicity. The niraparib doses were based on baseline body weight and platelet count.
To be eligible for enrollment, patients had to have newly diagnosed FIGO stage IIIb to IV ovarian cancer who had achieved a complete response (CR) or PR to first-line platinum-based chemotherapy and bevacizumab. Patients who received neoadjuvant chemotherapy and/or primary debulking surgery were also eligible.
All patients were tested for homologous recombination deficiency (HRD) or proficiency at the time of enrollment; 47% of patients had HRD, which included those withBRCA-mutant andBRCAwild-type disease. The median age of the participants was 60 years, and the median body weight was 68 kg. Sixty-three percent of patients received neoadjuvant chemotherapy, 79% of patients had stage III disease, 49% had pre-existing hypertension, and 95% of patients had serous histology. Seventy-eight percent of patients started niraparib at the 200-mg dose.
The primary end point of the trial is 18-month PFS from the initiation of treatment. The interim analysis included 6-month PFS rates from treatment initiation after all patients had undergone 2 scans following treatment.
Secondary end points of the trial included 24-month PFS rates, 24-month overall survival (OS) rates, RECIST or CA-125 PFS, patient-reported outcomes, time to first subsequent therapy, time to second subsequent therapy, and safety.
Additionally, health-related quality of life is measured by ECOG. Safety and tolerability will be assessed by clinical review of adverse events (AEs), physical examinations, electrocardiograms, RECIST tumor assessments, and safety laboratory values.
Regarding safety, grade ≥3 treatment-emergent AEs associated with the combination included thrombocytopenia, anemia, and hypertension. In the abstract, investigators noted that the safety profile of the combination mirrored that of the phase I/II AVANOVA trial, which also evaluated the combination of niraparib and bevacizumab in patients with platinum-sensitive epithelial ovarian cancer.
In the randomized, phase II AVANOVA study, niraparib plus bevacizumab doubled PFS versus niraparib alone at 11.9 months and 5.5 months, respectively, in patients with platinum-sensitive recurrent ovarian cancer (HR, 0.35; 95% CI, 0.21-0.57;P<.0001).2Moreover, at a median follow-up of 16.9 months, patients who had a prior platinum-free interval (PFI) of 6 to 12 months (11.3 vs 2.2 months, respectively; HR, 0.29; 95% CI, 0.14-0.62;P= .0006) or >12 months (13.1 vs 6.1 months; HR, 0.42; 95% CI, 0.20-0.80;P= .0062) derived similar benefit from the combination.
The doublet also had activity in patients with or without HRD and those with or withoutBRCAmutations. In HRD-positive tumors, the median PFS was 11.9 months with the combination and 6.1 months with niraparib alone (HR, 0.38; 95% CI, 0.20-0.72;P= .0019). In HRD-negative disease, the median PFS was 11.3 months and 4.2 months with niraparib/bevacizumab and niraparib alone, respectively (HR, 0.40; 95% CI, 0.19-0.85;P= .0129).
In patients withBRCA-mutant tumors, the median PFS was 14.4 months versus 9.0 months with the combination and single-agent niraparib, respectively (HR, 0.49; 95% CI, 0.21-1.15;P= .0947). The median PFS was 11.3 months with niraparib/bevacizumab versus 4.2 months with niraparib alone in those withBRCAwild-type tumors (HR, 0.32; 95% CI, 0.17-0.58;P= .0001).
The overall response rates and disease control rates were 60% and 79% with the combination, respectively, versus 27% and 53% with single-agent niraparib.
Grade ≥3 AEs occurred in 65% of patients who received the combination compared with 45% of those on niraparib alone, the most common being anemia (15% vs 18%, respectively) and thrombocytopenia (10% vs 12%), and hypertension (21% vs 0%).3Niraparib plus bevacizumab was associated with increased incidences of any-grade proteinuria (21% vs 0%) and hypertension (56% vs 22%) compared with niraparib alone. No treatment-related deaths were reported.
In October 2019, the FDA approved niraparib for the treatment of patients with advanced ovarian, fallopian tube, or primary peritoneal cancer who have been treated with ≥3 prior chemotherapy regimens, and whose cancer is associated with HRD-positive status. The PARP inhibitor was initially approved in March 2017 for the maintenance treatment of adult patients with recurrent epithelial ovarian, fallopian tube, or primary peritoneal cancer who are in CR or PR to platinum-based chemotherapy.