Ovarian cancer is a leading cause of death from gynecologic cancers worldwide. A randomized, placebo-controlled, phase 3 trial conducted by Mirza et al. evaluated the efficacy and safety of niraparib versus placebo as maintenance treatment in a broad population of patients with platinum-sensitive, recurrent ovarian cancer. Among these patients, the use of niraparib, a PARP inhibitor, was associated with a significantly longer duration of progression-free survival than placebo, with moderate bone marrow toxicity. A new Original Article summarizes.
• What is the usual pattern of response to platinum and taxane treatment in patients with advanced ovarian cancer?
Despite a high initial response rate to platinum and taxane treatment in patients with advanced cancer, the effectiveness of the treatments diminishes over time, and most patients have a relapse. Platinum retreatment is used in patients in whom there is an assumed platinum sensitivity, with diminishing effectiveness and a cumulative increase in toxicity.
• To what class of drugs does niraparib belong?
Niraparib is a highly selective inhibitor of poly (adenosine diphosphate [ADP]–ribose) polymerase (PARP) 1/2, nuclear proteins that detect DNA damage and promote its repair. Clinical studies have evaluated PARP inhibitors in patients with recurrent ovarian cancer, including those with germline BRCA mutations, platinum-sensitive disease, or both.
Morning Report Questions
Q: Does niraparib maintenance therapy prolong progression-free survival in patients with platinum-sensitive, recurrent ovarian cancer?
A: The trial by Mirza et al. enrolled two independent cohorts on the basis of the presence or absence of a germline BRCA mutation (gBRCA cohort and non-gBRCA cohort). Before the database lock, tumor testing of archived tissue samples was performed with the use of a central laboratory DNA-based test to define the population of patients in the non-gBRCA cohort in whom tumors were found to have homologous recombination deficiency (HRD). Such patients were included in the non-gBRCA HRD-positive subgroup. (Decreased rates of homologous recombination have been found to cause inefficient DNA repair.) The three predefined primary efficacy populations were the gBRCA cohort, the HRD-positive subgroup of the non-gBRCA cohort, and the overall non-gBRCA cohort. The authors found that niraparib had a positive effect among patients with platinum-sensitive recurrent ovarian cancer. The duration of progression-free survival in patients with platinum-sensitive, recurrent ovarian cancer was significantly longer in the niraparib group than in the placebo group, regardless of the presence or absence of gBRCA mutations or HRD status.
Q: What adverse events were associated with niraparib in the trial by Mirza et al.?
A: In the trial by Mirza et al., Grade 3 or 4 hematologic events that were observed in at least 10% of patients receiving niraparib were thrombocytopenia (in 33.8%), anemia (in 25.3%), and neutropenia (in 19.6%). Treatment discontinuations because of these events were infrequent. Most of the hematologic laboratory abnormalities occurred within the first three treatment cycles; after dose adjustment on the basis of an individual adverse-event profile, the incidence of grade 3 or 4 thrombocytopenia, neutropenia, or fatigue was infrequent beyond cycle 3.