Phase III PRIMA Trial Shows PFS Benefit With Niraparib as First-Line Maintenance in Ovarian Cancer

Hal Barron, MD

Hal Barron, MD

In the phase III PRIMA (ENGOT-OV26) trial (NCT02655016), niraparib (Zejula) demonstrated a benefit in progression-free survival (PFS) compared with placebo when used as maintenance therapy following platinum-based chemotherapy for patients with ovarian cancer treated in the first line.¹The PFS benefit was found to be statistically significant, regardless of patients’ biomarker status, meeting the primary endpoint of the trial.

“Almost 300,000 women around the world are diagnosed with ovarian cancer every year, yet only about 15% of patients are currently eligible to receive PARP inhibitors as their initial therapy. These exciting data demonstrate that Zejula has the potential to significantly benefit even more women with this devastating cancer,” said Hal Barron, MD, chief scientific officer and president, Research and Development, GlaxoSmithKline (GSK), in a statement.

Initial positive results from the PRIMA trial also extended to the safety and tolerability profile of niraparib, which was consistent with prior reports of the PARP inhibitor.

Full findings from the trial will be presented at an upcoming scientific meeting, GSK, the company developing niraparib, announced.

The double-blind, placebo-controlled, randomized phase III trial is exploring the use of niraparib versus placebo in patients with first-line stage III or IV ovarian cancer. The study has completed enrollment but is continuing to study the results.

In the trial, patients who had completed frontline platinum-based chemotherapy with either a complete response or partial response to therapy were randomized 2:1 to either maintenance niraparib or placebo.

Patients were required to have high-grade predominantly serous or endometrioid ovarian cancer, fallopian tube cancer, or primary peritoneal cancer. Platinum-based chemotherapy could have been given as either an adjuvant or neoadjuvant treatment regimen. Additionally, the women in the trial also had to have a normal or above 90% decrease in CA-125 following their frontline regimen. Patients with stage IV disease were only eligible for enrollment after primary or interval debulking.

Women with mucinous or clear cell subtypes, as well as those who had received a prior PARP inhibitor or bevacizumab (Avastin), were ineligible for enrollment in the trial.

The primary endpoint of the trial is PFS and secondary endpoints include overall survival, safety and tolerability, time to progression on subsequent therapy, and patient-reported outcomes. Additional outcome measures include pharmacokinetics and homologous recombination deficiency (HRD) biomarker testing.

According to interim safety results presented at the 2019 SGO Annual Meeting,²patients benefited from fewer adverse events (AEs) when treated with an individualized starting dose of 200- or 300-mg based on their body weight compared with those who received a fixed dose of 300 mg.  

Treatment-emergent AEs (TEAEs) decreased among any TEAE (92.7% vs 97.5%, respectively), those leading to treatment interruption (50.6% vs 60.3%), any grade 3 TEAE (42.5% vs 55.5%), those leading to dose reduction (39.7% vs 51.6%), and any serious AE (21.5% vs 26.6%) with the individualized dosing, compared with fixed dosing. However, TEAEs leading to discontinuation of treatment was higher among those treated with the individualized approach (10.5% vs 7.5%).

Similarly, grade ≥3 hematologic toxicities decreased with individualized dosing, including an approximate 60% decrease in thrombocytopenia (9.7% vs 23.5%, respectively) and an approximate 40% decrease in neutropenia (6.1% vs 10.0%), compared with the fixed dose. In addition, grade ≥3 anemia decreased to 13.8% among those treated with the individualized approached versus 22.7% in the fixed dosing arm. Of note, there was an approximate 80% reduction in grade 4 thrombocytopenia (3.6% vs 16.8%) with the individualized dosing. 

Symptomatic TEAEs also decreased with the individualized dosing regimen, including nausea (40.5% vs 48.6%), fatigue (30.0% vs 31.4%), insomnia (16.2% vs 21.8%), vomiting (14.2% vs 19.5%), and hypertension (10.1% vs 12.3%) of any grade.

Niraparib has been approved by the FDA for the maintenance treatment of patients with recurrent ovarian cancer who had a complete or partial response to platinum therapy, regardless ofBRCAor HRD status.

References

1. GSK announces positive headline results in Phase 3 PRIMA study of ZEJULA (niraparib) for patients with ovarian cancer in the first line maintenance setting [press release]. London, UK: GlaxoSmithKline plc; July 15, 2019. https://bit.ly/2YTFO6h. Accessed July 15, 2019.
2. Monk BJ, Mirza MR, Vergote I, et al. A prospective evaluation of tolerability of niraparib dosing based upon baseline body weight and platelet count: Blinded pooled interim safety data from the ENGOT-OV26/PRIMA study. Presented at: 2019 SGO Annual Meeting. March 16-19, 2019; Honolulu, HI. Abstract 3.