November 2016, Vol. 5, No. 9
Practice-Changing Study Shows Niraparib Extends Progression-Free Survival in Platinum-Sensitive Ovarian Cancer
Maintenance therapy with niraparib, an investigational oral PARP inhibitor, significantly prolonged progression-free survival (PFS) in patients with recurrent platinum-sensitive ovarian cancer regardless of BRCA 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 lead author Mansoor Raza Mirza, MD, Rigshospitalet, Copenhagen, Denmark.
Dr Mirza presented these groundbreaking results from the ENGOT-OV16/NOVA trial at the European Society for Medical Oncology 2016 Congress.
He said that olaparib is a PARP inhibitor approved for tumors with the germline BRCA (gBRCA) mutation, which is present in about 20% of ovarian cancers. “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 ovarian cancer at relapse is 6 courses of chemotherapy. The disease typically recurs, and then the relapse-free intervals become progressively shorter until patients die of the disease. The rationale for maintenance therapy is to extend the interval from one round of therapy to the next with a less toxic treatment.
ENGOT-OV16/NOVA was a global study that enrolled 553 patients with platinum-sensitive ovarian cancer who responded to standard-of-care platinum-based treatment and then relapsed. Patients were randomized in a 2:1 ratio to receive niraparib 300 mg/day or placebo and treated until disease progression. Patients were classified at enrollment as having either gBRCA-mutated ovarian cancer (n = 203) or non–gBRCA-mutated ovarian cancer (n = 350). There were no baseline imbalances in demographic or clinical factors betweeen gBRCA-mutated patients and non–gBRCA-mutated patients.
The study met the primary end point of significant improvement in PFS for niraparib versus placebo, with a 73% improvement in PFS in the gBRCA group: median PFS was 21 months versus 5.5 months, respectively (P <.0001). In non-gBRCA patients, niraparib improved PFS by 55% over placebo: median PFS was 9.3 months versus 3.9 months, respectively (P <.0001). In a subgroup of the non-gBRCA group with HRDs, niraparib also significantly improved PFS to 12.9 months from 3.8 months with placebo (P <.0001), representing a 62% improvement.
In an exploratory analysis, niraparib significantly improved PFS in HRD-negative patients, with a 42% reduction in risk of progression, he said.
There were no new safety signals. The most common adverse events related to niraparib included hematologic laboratory abnormalities and fatigue. Adverse events were well managed by dose interruptions or reductions. “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.
Additional trials are planned to study niraparib as first-line therapy in platinum-sensitive patients.
Niraparib was granted fast-track status by the FDA in September 2016.
The study was supported by Tesaro.
Formal discussant Sandro Pignata, MD, IRCCS National Cancer Institute, “Fondazione G. Pascale,” Naples, Italy, said: “This study represents a significant step forward in the treatment of recurrent ovarian cancer. Response to platinum is the key clinical parameter for selection of patients for niraparib.”
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