Niraparib Maintenance Therapy in Patients With Recurrent Ovarian Cancer After a Partial Response to the Last Platinum-Based Chemotherapy in the ENGOT-OV16/NOVA Trial

Abstract

PURPOSE In the ENGOT-OV16/NOVA trial (ClinicalTrials.gov identifier: NCT01847274 ), maintenance therapy with niraparib, a poly(ADP-ribose) polymerase inhibitor, prolonged progression-free survival in patients with platinum-sensitive, recurrent ovarian cancer who had a response to their last platinum-based chemotherapy. The objective of the study was to assess the clinical benefit and patient-reported outcomes in patients who had a partial response (PR) and complete response (CR) to their last platinum-based therapy. PATIENTS AND METHODS A total of 553 patients were enrolled in the trial. Of 203 patients with a germline BRCA mutation (g BRCAmut), 99 had a PR and 104 had a CR to their last platinum-based therapy; of 350 patients without a confirmed g BRCAmut (non–g BRCAmut), 173 had a PR and 177 had a CR. Post hoc analyses were carried out to evaluate safety and the risk of progression in these patients according to g BRCAmut status and response to their last platinum-based therapy. Ovarian cancer–specific symptoms and quality of life were assessed using the Functional Assessment of Cancer Therapy–Ovarian Symptom Index. RESULTS Progression-free survival was improved in patients treated with niraparib compared with placebo in both the g BRCAmut cohort (PR: hazard ratio [HR], 0.24; 95% CI, 0.131 to 0.441; P < .0001; CR: HR, 0.30; 95% CI, 0.160 to 0.546; P < .0001) and the non–g BRCAmut cohort (PR: HR, 0.35; 95% CI, 0.230 to 0.532; P < .0001; CR: HR, 0.58; 95% CI, 0.383 to 0.868; P = .0082). The incidence of any-grade and grade 3 or greater adverse events was manageable. No meaningful differences were observed between niraparib and placebo in PR and CR subgroups with respect to patient-reported outcomes. CONCLUSION Patients achieved clinical benefit from maintenance treatment with niraparib regardless of response to the last platinum-based therapy.

Germline and Somatic <i>BRCA1/2</i> Gene Mutational Status and Clinical Outcomes in Epithelial Peritoneal, Ovarian, and Fallopian Tube Cancer: Over a Decade of Experience in a Single Institution in Korea

“…The advent of treatment strategies involving the two PARP inhibitors olaparib and niraparib for POFTC has increased the demand for BRCA1/2 gene testing in Korea. Based on the findings that tumors with somatically acquired BRCA1 or BRCA2 pathogenic mutations respond to PARP inhibitors [10][11][12], physicians at our institution are recommending somatic testing to patients harboring wild-type BRCA1/2 according to germline test results and vice versa in order to expand candidate options for PARP inhibitors. As a result, 57 patients from the study population received both germline and somatic tests.…”

“…Offspring of a germline BRCA1/2mutation carrier have a 50% chance of inheriting the patho-genic or likely pathogenic variant. Moreover, patients harboring germline or somatic BRCA1/2 mutations with primary or platinum-sensitive relapsed POFTC experience positive survival outcomes from poly(ADP-ribose) polymerase (PARP) inhibitors based on their synthetic lethality [7][8][9][10][11][12]. Therefore, current guidelines from the Korean Society of Gynecologic Oncology recommend that patients with epithelial POFTC patients undergo BRCA1/2 gene testing [13].…”

Clinical Implications of DNA Repair Defects in High-Grade Serous Ovarian Carcinomas

“…When compared with placebo in nested patient subpopulation analyses, both Rucaparib and Niraparib showed a declining trend of efficacy in terms of improved PFS: the most appealing results were achieved by patients with BRCA-mutant carcinomas, with a gradually weakening effect in the HRD-positive and the intention-to-treat populations. Despite this unequivocal tendency, focusing on BRCA-WT HGSOCs harboring other-than-BRCA mutations impairing the DNA homologous recombination system, the aforementioned PARP inhibitors significantly lowered the risk for disease progression with respect to placebo, highlighting how the HRD status may provide predictive information about the potential treatment benefit deriving from PARPis-mediated synthetic lethality [38,39,42].…”

The value of secondary neoadjuvant chemotherapy in platinum-sensitive recurrent ovarian cancer: a case-control study post GOG-0213 trial

“…Presently, combination Platinum based chemotherapy with or without antiangiogenic agents is deemed the main approach in therapy for PSOC [26]. The following PARP inhibitors maintenance therapy following complete or partial remission cases was deemed to be the latest development in this subgroup [27][28][29][30][31]. However, SCR may also have the irreplaceable role in the management of some recurrent ovarian cancer under special circumstances [32].…”