Study Further Characterizes Niraparib PFS Benefit in Ovarian Cancer

Mansoor Raza Mirza, MD

Patients with ovarian cancer who had a partial response (PR) to previous platinum-based therapy had superior progression-free survival (PFS) with or without germline BRCA mutations after treatment with niraparib (Zejula), according to a posthoc analysis of 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 niraparib 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 4 cycles in ENGOT-OV16/NOVA, a phase III multicenter, randomized, double-blind, placebo-controlled study.

At the time of unblinding, 45% in the niraparib group who were positive for mutant BRCA achieved PFS, compared with 72% of patients in the placebo group (HR, 0.24; 95% CI, 0.131-0.441). In the non-BRCA mutant cohort, 56% of patients had PFS versus 80% in the placebo group (HR, 0.35; 95% CI, 0.230-0.532).

“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, MD, 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 OncLive. “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 (n = 272) 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 niraparib daily or placebo until disease progression or unacceptable toxicity. In the germline mutant BRCA cohort, 67 out of 138 patients in the niraparib arm (49%) and 32 out of 65 patients in the placebo arm (48%) entered the trial with a PR. In the non-mutant germline BRCA cohort, 117 out of 234 patients in the niraparib arm (50%) and 56 out of 116 in the placebo arm (48%) 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 bevacizumab (Avastin), and the best response (CR or PR) during the final platinum regimen. Each patient had received at least 2 prior courses of platinum-based chemotherapy but no prior treatment with a PARP inhibitor.

Disease assessment included imaging performed at baseline every 8 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 niraparib-treated patients with a PR was similar to that of the overall study population. The concluded that, overall, treatment with niraparib 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 niraparib 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 niraparib reduced the risk of progression or death by 74% compared with placebo for patients with germline BRCA-positive platinum-sensitive, recurrent ovarian cancer.

The median PFS with maintenance niraparib was 21 months compared with 5.5 months for placebo in patients with germline BRCA mutations (HR, 0.26; 95% CI, 0.17-0.41; P <.0001). These findings remained consistent across subgroups of patients, including those without BRCA mutations.

Mirza RM, Monk B, Gil-Martin M, et al. Efficacy of niraparib on progression-free survival (PFS) in patients (pts) with recurrent ovarian cancer (OC) with partial response (PR) to the last platinum-based chemotherapy. J Clin Oncol. 35 2017;35. (suppl; abstr 5517).