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ESMO 2016: Niraparib Significantly Improves Outcomes in Platinum-Sensitive Recurrent Ovarian Cancer

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Key Points

  • Median progression-free survival with niraparib compared to placebo was 21.0 vs 5.5 months in the germline BRCA mutation group, 9.3 months vs 3.9 months in the nongermline BRCA mutation group, and 12.9 vs 3.8 months in a subgroup of the nonmutation cohort who had homologous recombination DNA repair deficiencies.
  • Compared to placebo, niraparib significantly prolonged the second progression-free survival, time to first subsequent treatment, and chemotherapy-free interval in the mutation and mutation-free groups, as well as in the HRD subgroup.
  • More than 10% of patients had grade 3/4 adverse events following treatment with niraparib, of whom 28% had thrombocytopenia, 25% had anemia, and 11% had neutropenia. These were resolved with dose adjustments.

The PARP inhibitor niraparib significantly improves the outcome of platinum-sensitive recurrent ovarian cancer, according to full data from the ENGOT-OV16/NOVA trial presented by Mirza et al at the 2016 European Society for Medical Oncology (ESMO) Congress in Copenhagen (Abstract LBA3_PR), and published by Mirza et al in The New England Journal of Medicine. The trial met its primary endpoint, with niraparib considerably prolonging progression-free survival compared to placebo.

“There are limited treatment options in recurrent ovarian cancer,” said lead author Mansoor Raza Mirza, MD, Chief Oncologist at Rigshospitalet, Copenhagen University Hospital and Medical Director of the Nordic Society of Gynaecological Oncology. “Cumulative toxicity with platinum-based chemotherapy and lack of additional benefit limit its use. We then pause treatment until the next relapse and start combination chemotherapy.”

“The current options for maintenance therapy in the European Union (EU) are bevacizumab [Avastin]—which can only be given once and improves progression-free survival by just a few months—and the PARP inhibitor olaparib [Lynparza], which is only approved in patients with a germline BRCA mutation (about 10%–15% of ovarian cancer patients). No maintenance therapy is approved outside the EU,” he continued.

ENGOT-OV16/NOVA

This phase III trial was performed in collaboration with the European Network of Gynaecological Oncology Trial groups (ENGOT). The ENGOT-OV16/NOVA trial evaluated the efficacy and safety of the PARP inhibitor niraparib as maintenance therapy in patients with recurrent ovarian cancer who respond to platinum-based chemotherapy. Patients were assigned to cohorts by BRCA mutation status and randomized 2:1 to receive niraparib at 300 mg or placebo once daily.

The trial included 553 patients, of whom 203 had the germline BRCA mutation and 350 did not. Niraparib significantly improved the primary endpoint of progression-free survival compared to placebo in both cohorts, as well as in all subgroups.

Median progression-free survival with niraparib compared to placebo was 21.0 vs 5.5 months in the germline BRCA mutation group (hazard ratio [HR] = 0.27, 95% confidence interval [CI] = 0.173–0.410, < .0001); 9.3 vs 3.9 months in the nongermline BRCA mutation group (HR = 0.45, 95% CI = 0.338–0.607, < .0001); and 12.9 vs 3.8 months in a subgroup of the nonmutation cohort who had homologous recombination DNA repair deficiencies, or HRD (HR = 0.38, 95% CI = 0.243–0.586, < .0001).

Adverse Events

More than 10% of patients had grade 3/4 adverse events following treatment with niraparib, of whom 28% had thrombocytopenia, 25% had anemia, and 11% had neutropenia. These were resolved with dose adjustments and patients could continue their treatment. Patient-reported outcomes were similar with niraparib and placebo. Patients on niraparib maintained symptom control and had a quality of life comparable to those on placebo.

Significant improvements were also observed in all secondary endpoints. Compared to placebo, niraparib significantly prolonged the second progression-free survival, time to first subsequent treatment, and chemotherapy-free interval in the mutation and mutation-free groups, as well as in the HRD subgroup.

“This is a breakthrough for patients with ovarian cancer,” said Dr. Mirza. “We have never seen such large benefits in progression-free survival in recurrent ovarian cancer. Niraparib significantly improved all endpoints across a broad patient population representing 70% of all ovarian cancer patients. These landmark results could change the way we treat this disease.”

He concluded: “Once it is approved by the regulatory authorities, I’ll consider niraparib for all my patients with recurrent ovarian cancer who respond to platinum, regardless of BRCA status.”

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.


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