Niraparib, a PARP inhibitor, has shown promise in extending progression-free survival and time to next treatment in patients with epithelial ovarian cancer, particularly those with homologous recombination-deficient tumors. Real-world data and clinical trials support its efficacy in both first-line maintenance and recurrent settings.
Niraparib Extends PFS and TTNT in EOC Patients
A recent study published in Future Oncology investigated the real-world outcomes of first-line maintenance (1LM) niraparib monotherapy in patients with epithelial ovarian cancer (EOC). The study, utilizing data from Flatiron Health, a US-based electronic health record database, found that patients with HRd tumors who received 1LM niraparib monotherapy experienced longer observed median rwPFS and rwTTNT, especially those with BRCA-mutated tumors.
The observed median rwPFS was 11.4 months in the overall population, but it extended to 18.2 months in the HRd subgroup. Among the HRd subgroup, patients with BRCAm tumors had an observed median rwPFS of 25.4 months, while those with BRCAwt tumors had 14.2 months. The observed median rwTTNT was 12.4 months in the overall population and 19.6 months in the HRd subgroup. Specifically, the observed rwTTNT was 24.9 months for patients with BRCAm tumors and 15.1 months for patients with BRCAwt tumors.
Improved Outcomes in Stage III EOC with No Visible Residual Disease
Another study in Oncology and Therapy highlighted the benefits of niraparib in patients with stage III EOC and no visible residual disease (NVRD) after primary cytoreductive surgery (PCS). The study found that these patients had significantly longer real-world time to next treatment (rwTTNT) and progression-free survival (rwPFS) compared to those with higher-risk prognostic factors for disease progression.
The observed median rwTTNT in the stage III NVRD cohort was 22.5 months, almost twice as long as that in the PRIMA-like cohort (11.7 months; P < .001). The observed median rwPFS in the stage III NVRD cohort was 25.2 months, over twice as long as that in the PRIMA-like cohort (10.1 months; P < .001).
Niraparib's Role in Advanced Ovarian Cancer Treatment
Niraparib is a PARP inhibitor that disrupts DNA repair after damage occurs during the cell cycle. It has received FDA approval for first-line maintenance therapy in patients with advanced EOC following platinum-based chemotherapy, regardless of their molecular profile. The approval was based on the results of the PRIMA/ENGOT-OV26 trial, a Phase 3 randomized, double-blind clinical trial that assessed the efficacy and safety of niraparib in the first-line maintenance setting for patients with newly diagnosed advanced EOC.
The trial population comprised individuals diagnosed with high-grade serous or endometrioid histology and achieving complete or partial response to platinum-based chemotherapy. Patients were randomized 2:1 to receive daily niraparib (300mg) or placebo for 36 months or until disease progression. Progression-free survival (PFS) was the primary endpoint, evaluated in the overall patient population and the HRD-positive subgroup. Patients harboring HRD-positive tumors exhibited a significant 57% reduction in disease progression or death compared to the placebo arm. Notably, even patients lacking HRD status demonstrated a substantial 38% reduction in disease progression or death.
Safety and Tolerability
The most common adverse events associated with niraparib treatment include hematologic toxicities (anemia, neutropenia, thrombocytopenia), gastrointestinal disturbances (nausea, vomiting, diarrhea, constipation), and fatigue. Thrombocytopenia is a distinct adverse event, and a post-hoc analysis of the NOVA trial revealed that patients with lower body weight or baseline platelet count might benefit from initiating therapy with a reduced dose. New-onset hypertension has also been reported in patients receiving niraparib, and treatment protocols for hypertension should be followed. Niraparib treatment carries a risk of developing myelodysplastic syndrome or acute myeloid leukemia (MDS/AML), a rare but severe toxicity.
Conclusion
Niraparib has emerged as a valuable tool in the treatment of EOC, demonstrating its ability to prolong progression-free survival, particularly in the frontline setting. Its efficacy in patients with BRCA mutations or HRD-positive tumors is well-established, and ongoing research aims to refine its use in recurrent disease and optimize patient selection. The drug's broad approval for frontline maintenance therapy underscores its importance in improving outcomes for women with advanced ovarian cancer.
