Niraparib is a poly (ADP-ribose) polymerase (PARP) inhibitor approved in the United States and European Union for maintenance treatment of patients with advanced or platinum-sensitive, recurrent ovarian cancer. It is also approved in the United States for the treatment of patients with ovarian cancer who have received ≥3 prior chemotherapy regimens and whose cancer is associated with BRCA mutation or homologous recombination–deficient platinum-sensitive disease. The PRIMA/ENGOT-OV26/GOG-3012 trial demonstrated that niraparib significantly improves progression-free survival in patients with newly diagnosed advanced ovarian cancer that responded to first-line platinum-based chemotherapy. Researchers reported the efficacy of niraparib in patients by BRCA wild-type status.
In this double-blind, placebo-controlled, phase 3 trial, niraparib was evaluated in patients with newly diagnosed, advanced, high-grade serous or endometrioid ovarian, primary peritoneal, or fallopian tube cancer. Eligible patients had achieved a complete or partial response to first-line platinum-based chemotherapy. Patients were stratified by best response to first-line chemotherapy, receipt of neoadjuvant chemotherapy, and homologous recombination status. Patients were randomized to receive either niraparib or placebo once daily. The primary end point was progression-free survival, which was assessed by blinded independent central review.
Of 733 patients randomized in the trial, 473 had BRCA wild-type tumors. Of these, 149 (31.5%) had homologous recombination–deficient BRCA wild-type tumors, 245 (51.8%) had homologous recombination–proficient BRCA wild-type tumors, and 79 (16.7%) had homologous recombination not determined BRCA wild-type tumors. Patients with BRCA wild-type tumors treated with niraparib demonstrated a progression-free survival benefit, regardless of homologous recombination status. Patients with homologous recombination–deficient tumors who received niraparib had a median progression-free survival of 19.6 months compared with 8.2 months for those receiving placebo. Similarly, for patients with homologous recombination–proficient tumors, patients receiving niraparib had a median progression-free survival of 8.2 months compared with 5.4 months for patients receiving placebo.
Patient-reported outcome measurements demonstrated that quality of life was maintained for patients with BRCA wild-type tumors. There was no difference found in Functional Assessment of Cancer Therapy–Ovarian Symptom Index (FOSI) and European Quality of Life 5-Dimension 5-Level Questionnaire (EQ-5D-5L) scores between patients receiving niraparib and those receiving placebo.
Researchers concluded that niraparib improved progression-free survival when used as maintenance therapy in patients with newly diagnosed, advanced ovarian cancer with BRCA wild-type tumors following first-line platinum-based chemotherapy. This improvement was noted regardless of homologous recombination status, including in patients with homologous recombination–proficient BRCA wild-type tumors.
Abstract 364. ESGO 2020.