Copenhagen, Denmark—Maintenance therapy with niraparib, an oral PARP inhibitor, significantly prolonged progression-free survival (PFS) in patients with recurrent, platinum-sensitive ovarian cancer regardless of their BRCA mutation status and homologous recombination deficiency (HRD) status.
“This is a breakthrough for patients with ovarian cancer. We have never seen such large benefits in progression-free survival in recurrent ovarian cancer. Niraparib significantly improved all end points across a broad patient population, representing about 70% of all ovarian cancer patients. These landmark results could change the way we treat this disease,” said investigator Mansoor Raza Mirza, MD, Department of Oncology, Rigshospitalet-Copenhagen University Hospital, Denmark. He presented the groundbreaking results of the ENGOT-OV16/NOVA trial at the 2016 European Society for Medical Oncology Congress.
The PARP inhibitor olaparib (Lynparza) is approved by the FDA for patients with ovarian cancer and the BRCA mutation, which is present in approximately 10% to 15% of patients with the disease.
“A much higher percentage of patients will benefit from niraparib compared with olaparib. In this trial, overall survival is improved by 26% with niraparib, which is a beautiful result. This is a huge benefit in the whole study population—those with the BRCA mutations and those without,” Dr Mirza said.
Standard treatment for patients with ovarian cancer relapse is 6 courses of chemotherapy. The disease typically recurs, and the relapse-free intervals become progressively shorter. The rationale for maintenance therapy is to extend the interval from 1 round of therapy to the next, with a treatment that has less severe side effects.
The phase 3 ENGOT-OV16/NOVA trial was a global study that enrolled 553 patients with ovarian cancer who responded to standard-of-care, platinum-based treatment and then relapsed (ie, platinum-sensitive). The patients were randomized in a 2:1 ratio to receive niraparib 300 mg daily or placebo until disease progression. Patients were divided into 2 groups based on ovarian cancer plus BRCA mutation (N = 203) or ovarian cancer with no mutation (N = 350).
The study met the primary end point of significant improvement in PFS for niraparib versus placebo, with a 73% improvement in PFS in the BRCA group; the median PFS was 21 months with niraparib versus 5.5 months with placebo. In the non-BRCA group, niraparib improved PFS by 55% over placebo: median PFS was 9.3 months versus 3.9 months, respectively. In a subgroup of the patients with HRD but no BRCA mutation, niraparib also significantly improved PFS to 12.9 months versus 3.8 months with placebo, representing a 62% improvement.
In an exploratory analysis, niraparib significantly improved PFS in HRD-negative patients, with a 42% reduction in risk for progression, Dr Mirza said.
There were no new safety signals. The most common adverse events related to niraparib included hematologic laboratory abnormalities and fatigue.
“Patients were able to maintain treatment until disease progression with no detrimental effect on quality of life according to patient-reported outcomes. The efficacy of treatment was durable,” he said. Adverse events were well-managed by dose interruptions or reductions.
Niraparib was granted fast-track status by the FDA in September 2016. Ongoing trials are planned to study niraparib as upfront therapy in patients with platinum-sensitive cancer.
“This study represents a significant step forward in the treatment of recurrent ovarian cancer,” said formal discussant Sandro Pignata, MD, IRCCS National Cancer Institute Fondazione G. Pascale, Naples, Italy.
“Response to platinum is the key clinical parameter for selection of patients for niraparib,” he concluded.
