1. Niraparib, a PARP (polyadenosine diphosphate ADP-ribose polymerase) inhibitor, has been associated with an increase in progression-free survival among patients with recurrent ovarian cancer.
2. In this phase 3 trial, patients with newly diagnosed advanced ovarian cancer who received niraparib had a significantly longer progression-free survival than those who received placebo.
Evidence Rating Level: 1 (Excellent)
Study Rundown: Ovarian cancer has a high mortality rate worldwide and up to 85% of those treated with chemotherapy have disease recurrence. Data on bevacizumab maintenance therapy is limited. Olaparib has been associated with longer progression-free survival among patients with BRCA-mutated tumors. Niraparib, a PARP1 and PARP2 inhibitor, has been approved for maintenance therapy among patients with recurrent ovarian cancer with and without BRCA mutations. This randomized, phase 3 trial assessed the effect of niraparib in patients with newly diagnosed advanced ovarian cancer after treatment with a platinum-based chemotherapy. Participants were followed to determine progression-free survival, overall survival, and adverse events of niraparib. The median progression-free survival was higher among patients in the niraparib groups as compared to the placebo groups. In addition, the estimated 24-month survival was higher in the niraparib groups. The most common adverse effects were anemia, thrombocytopenia, and neutropenia. No deaths were reported and no difference in quality-of-life scores were found between the groups. This well-designed trial shows the effectiveness of niraparib as maintenance therapy in preventing ovarian cancer recurrence in patients after receiving chemotherapy. Further research needs to be done to determine the long-term efficacy of niraparib.
In-Depth [randomized controlled trial]: This randomized, double-blind, phase 3 trial was conducted in 20 countries between July 2016 and June 2018 with a total of 733 participants. Participants were 18 years of age or older with newly diagnosed stage III or IV ovarian cancer that had received platinum-based chemotherapy with partial or complete response. Participants were assessed for a homologous-recombination deficiency (HRD), defined as the presence of a BRCA deleterious mutation, and considered as part of the overall population if they did not have this mutation. Participants were randomly assigned to receive oral niraparib or placebo for 36 months and followed via imaging for disease recurrence. The primary outcome was progression-free survival in those with HRD mutation and in those without the HRD mutation. The secondary outcomes were overall survival and safety. 50.9% of participants had tumors with HRD. The median progression-free survival in patients with the HRD mutation was 21.9 months with niraparib and 10.4 months with placebo (hazard ratio 0.43; 95% CI, 0.31 to 0.59; P<0.001). Overall survival was higher in these patients with an estimated 24-month survival of 91% in the niraparib group and 85% in the placebo group. In patients without the HRD mutation, median progression-free survival was 13.8 months with niraparib and 8.2 months with placebo (hazard ratio, 0.62; 95% CI, 0.50 to 0.76; P<0.001). Overall estimated 24-month survival in this group was 84% in the niraparib group and 77% in the placebo group. The most common adverse effects of niraparib were anemia (31%), thrombocytopenia (28.7%), and neutropenia (12.8%). Myelosuppression was the primary reason for discontinuation.
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