Niraparib, a poly(ADP-ribose) polymerase (PARP) inhibitor, has demonstrated a sustained benefit in patients with recurrent, platinum-sensitive ovarian cancer, regardless of BRCA mutation status. The findings come from the phase 3 NOVA trial, which evaluated niraparib as maintenance therapy following platinum-based chemotherapy.
The NOVA trial was a randomized, double-blind, placebo-controlled study that enrolled 553 patients with recurrent ovarian, fallopian tube, or primary peritoneal cancer. Participants had to have received at least two prior platinum-based regimens and demonstrated sensitivity to platinum-based treatment. Patients were randomized in a 2:1 ratio to receive either oral niraparib (300mg daily) or placebo. The primary endpoint was progression-free survival (PFS), assessed by blinded central radiological and clinical review.
The results of the NOVA trial showed a statistically significant and clinically meaningful improvement in PFS with niraparib compared to placebo. The trial enrolled two independent cohorts on the basis of the presence or absence of a germline BRCA (gBRCA) mutation. In the gBRCA mutation cohort, the median age was 57 years (range 36 to 83) in niraparib arm and 58 years (range 38 to 73) in placebo arm. The median age of pts without gBRCA mutation was 63 years (range 33 to 84) in NIR arm and 61 years (range 34 to 82) in PLB arm. Overall, 210/533 (38%) pts had gBRCA mutation: 128 (23%) had BRAC1, and 69 (13%) had BRAC2. 40% of the patients in the non‐gBRCA cohort were assumed to have an HRD‐positive tumour. Overall 49.2% of pts had a partial response to the most recent platinum therapy. In the gBRCA mutation cohort, 48.6% were in NIR arm and 49.2% in PLB arm. In non gBRCA mutation cohort, 50% were in NIR arm, and 48.3% in PLB arm.
Efficacy Across Subgroups
Notably, niraparib demonstrated efficacy in both patients with and without germline BRCA mutations. This suggests that niraparib could be a valuable maintenance therapy option for a broader population of women with recurrent ovarian cancer, not just those with BRCA mutations. The study's design included stratification based on time to progression after the penultimate platinum regimen, use of bevacizumab, and best response during the last platinum regimen.
Safety and Tolerability
The safety profile of niraparib was manageable. Common adverse events included thrombocytopenia, anemia, and neutropenia, which were generally manageable with dose adjustments. The study's safety data were based on all patients who received at least one dose of niraparib or placebo.
Implications for Clinical Practice
The NOVA trial's findings support the use of niraparib as a maintenance therapy to extend remission in patients with recurrent, platinum-sensitive ovarian cancer. Given its efficacy across different patient subgroups, niraparib represents an important advance in the treatment paradigm for this challenging disease.
