Superior progression-free survival (PFS) was seen in patients with ovarian cancer who previously had a partial response (PR) to platinum-based therapy when they took Zejula (niraparib). This response was seen in patients with or without germline BRCA mutations, according to data from the ENGOT-OV16/NOVA trial presented at the 2017 ASCO Annual Meeting.
Investigators set out to explore the effect of the PARP inhibitor Zejula on PFS in patients with recurrent ovarian cancer who were in response (either complete response [CR] or PR) to their most recent platinum-based therapy after a minimum of our cycles in ENGOT-OV16/NOVA, a phase 3 multicenter, randomized, double-blind, placebo-controlled study.
At the time of unblinding, 45 percent in the Zejula group who were positive for mutant BRCA achieved PFS, compared with 72 percent of patients in the placebo group. In the non-BRCA mutant cohort, 56 percent of patients had PFS versus 80 percent in the placebo group.
“We had half of the population in both groups who had only partial remission and wanted to know how they were doing. We tried to show the patients who were in partial remission have the same PFS as the whole group,” lead investigator Mansoor Raza Mirza, M.D., chief oncologist in the Department of Oncology in Rigshospitalet, Copenhagen University Hospital, Denmark, and medical director of the Nordic Society of Gynecologic Oncology-Clinical Trial Unit, said in an interview with CURE. “PFS is actually better in the non-germline BRCA group because patients with active disease in the placebo group are progressing much faster so you see a better split as a hazard ratio [HR].”
Roughly half of the total study population (272 patients) responded to had a to their last platinum-based therapy. These patients were segregated by BRCA mutation status and assigned to either daily 300 mg Zejula daily or placebo until disease progression or unacceptable toxicity. In the germline mutant BRCA cohort, 67 out of 138 patients in the Zejula arm (49 percent) and 32 out of 65 patients in the placebo arm (48 percent) entered the trial with a PR.
In the non-mutant germline BRCA cohort, 117 out of 234 patients in the Zejula arm (50 percent) and 56 out of 116 in the placebo arm (48 percent) entered the trial with a PR. Randomization was further stratified based on time to progression after completion of the penultimate platinum regimen, the use of Avastin (bevacizumab), and the best response (CR or PR) during the final platinum regimen. Each patient had received at least two prior courses of platinum-based chemotherapy but no prior treatment with a PARP inhibitor.
Disease assessment included imaging performed at baseline every eight weeks through cycle 14, and then every 12 weeks until treatment was discontinued. Disease progression was determined via central review using RECIST v1.1 criteria or clinical assessment. Increased levels of CA-125 alone were not considered to indicate progression. Researchers determined that the safety profile of Zejula-treated patients with a PR was similar to that of the overall study population. The concluded that, overall, treatment with Zejula provided a statistically significant benefit in patients with a PR, with a treatment effect similar to that observed in the overall study population in both the germline BRCA mutant and non-mutant cohorts.
In March 2017, the FDA approved Zejula for the maintenance treatment of adult patients with recurrent epithelial ovarian, fallopian tube, or primary peritoneal cancer who are in complete or partial response to platinum-based chemotherapy.
The approval was based on the overall findings from the ENGOT-OV16/NOVA trial, in which Zejula reduced the risk of progression or death by 74 percent compared with placebo for patients with germline BRCA-positive platinum-sensitive, recurrent ovarian cancer.
The median PFS with maintenance Zejula was 21 months compared with 5.5 months for placebo in patients with germline BRCA mutations. These findings remained consistent across subgroups of patients, including those without BRCA mutations.
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