The PARP inhibitor niraparib (Zejula) provided significant benefits in patients with recurrent ovarian cancer who had a partial response, with similar treatment effects in patients with or without germline <em>BRCA</em> mutations, according to a post-hoc analysis of data from the ENGOT-OV16/NOVA trial presented at the 2017 ASCO Annual Meeting.
Mansoor Raza Mirza, MD
The PARP inhibitor niraparib (Zejula) provided significant benefits in patients with recurrent ovarian cancer who had a partial response (PR), with similar treatment effects in patients with or without germlineBRCAmutations, according to a post-hoc analysis of data from the ENGOT-OV16/NOVA trial presented at the 2017 ASCO Annual Meeting.
ENGOT-OV16/NOVA was a phase III multicenter, randomized, double-blind, placebo-controlled study that enrolled 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. The primary endpoint was progression free survival (PFS).
“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 Gynaecologic Oncology-Clinical Trial Unit, said in an interview withTargeted Oncology. “PFS is actually better in the non-germlineBRCAgroup because patients with active disease in the placebo group are progressing much faster so you see a better split as a hazard ratio [HR].”
In ENGOT-OV16/NOVA, 553 patients were assigned to 1 of 2 cohorts in a 2:1 ratio following germlineBRCAtesting for those with and without mutations to receive either 300 mg of niraparib daily or placebo disease progression or unacceptable toxicity. 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 of the patients 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.
Of the total 553 patients, 272 had a response to their last platinum-based therapy. In the germline mutantBRCAcohort, 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 germlineBRCAcohort, 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.
At the time of unblinding, 30 of the patients (45%) in the niraparib group of theBRCA-mutant cohort achieved PFS, compared with 23 of the patients (72%) in the placebo group (HR, 0.24; 95% CI, 0.131-0.441). In the non-BRCAmutant cohort, 65 of the patients (56%) versus 45 of the patients (80%) in the placebo group achieved PFS (HR, 0.35; 95% CI, 0.230-0.532).
The investigators concluded that the safety profile of niraparib-treated patients with a PR was similar to that of the overall study population. Overall they found that 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 germlineBRCAmutant and non-mutant cohorts.
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.2017;35. (suppl; abstr 5517).