1. Among patients with platinum-sensitive recurrent ovarian cancer, those who received the PARP inhibitor niraparib demonstrated significantly increased progression-free survival compared to patients who received placebo.
2. The most common treatment-emergent hematologic events reported included thrombocytopenia, anemia, and neutropenia.
Evidence Rating Level: 1 (Excellent)
Study Rundown: Selective inhibitors of poly(adenosine diphosphate [ADP]-ribose) polymerases (PARP), a family of nuclear proteins that are involved in DNA damage detection and repair, are an emerging class of antineoplastic drugs that have received significant attention in recent years for their success in the treatment of several cancers. This randomized trial involving patients with platinum-sensitive, recurrent ovarian cancer enrolled two independent cohorts on the basis of the presence or absence of gBRCA which is a germline of the BRCA mutation. Within each cohort, patients were randomly assigned in a 2:1 ratio to receive niraparib or placebo.
The study’s primary end point, progression-free survival (PFS), was defined as the time from randomization to earliest date of progression or death from any cause. This was assessed by serial pelvic CT or MRI scans. The primary endpoint was significantly lengthened in the niraparib group regardless of their gBRCA status. In both groups, the most common treatment emergent hematologic events reported were thrombocytopenia, anemia, and neutropenia.
This study draws strength from its strict inclusion criteria of patients with tumors bearing high-grade serous histologic features and who also experienced disease progression at >6 months after a demonstrated response to platinum-based chemotherapy, in addition to its standardized protocol for radiographic assessment of progression. Nonetheless, one limitation of the study was its relatively short median follow-up duration of 16.9 months.
In-Depth [randomized controlled trial]: This randomized, placebo-controlled, phase 3 trial assessed a primary end point of progression-free survival in patients with platinum-sensitive, recurrent ovarian cancer in a germline BRCA-mutant (gBRCA) and a non-germline BRCA-mutant cohort. Among the gBRCA cohort, median PFS was 21.0 months for the niraparib group compared to 5.5 months for the placebo group (HR 0.27; 95%CI 0.17 to 0.41; p < 0.001). A trend of increased survival was also observed in the non-gBRCA cohort. The non-gBRCA group showed 9.3 months of PFS in the niraparib group compared to 3.9 months in the placebo group (HR 0.45; 95%CI 0.34 to 0.61; p < 0.001). The most common treatment emergent hematologic events were thrombocytopenia (61.3% in the niraparib group vs. 5.6% in the placebo group), anemia (50.1% vs. 6.7%), and neutropenia (30.2% vs. 6.1%).
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