The PARP (poly [ADP-ribose] polymerase) inhibitor niraparib is safe for long-term use and effective as maintenance treatment in patients with platinum-sensitive recurrent ovarian cancer, according to data presented by Ursula A. Matulonis, MD, at the Society of Gynecologic Oncology (SGO) 2021 Virtual Annual Meeting on Women’s Cancer (Abstract ID 11139).
The final progression-free survival 2 analysis of the phase III ENGOT-OV16/NOVA study of niraparib maintenance vs placebo demonstrated that the benefit of niraparib maintenance therapy extended beyond first disease progression.
Based on adjusted analyses, a trend towards improved survival was also observed in patients with an underlying germline BRCA–mutated status receiving niraparib, with an increased survival of 9.7 months. However, the authors of the study cautioned that overall survival was a secondary endpoint and was therefore underpowered.
Ursula A. Matulonis, MD
Finally, long-term safety analysis showed a decrease in the number of hematologic adverse events after the first year of maintenance.
“These final data support the safe long-term use of niraparib for maintenance treatment in patients with platinum-sensitive recurrent ovarian cancer,” said Dr. Matulonis, Chief of the Division of Gynecologic Oncology at Dana-Farber Cancer Institute and Professor of Medicine at Harvard Medical School.
ENGOT-OV16/NOVA
ENGOT-OV16/NOVA was a randomized, double-blind, placebo-controlled phase III trial of niraparib maintenance treatment for patients with platinum-sensitive recurrent ovarian cancer. Patients with recurrent epithelial ovarian, fallopian tube, or primary peritoneal cancer following a complete response or partial response to platinum-based therapy were enrolled into one of two independent cohorts: germline BRCA–mutated and non-germline BRCA–mutated.
In a primary analysis of the trial published by Mirza et al in The New England Journal of Medicine, niraparib demonstrated a statistically significant improvement in progression-free survival regardless of germline status (non-germline BRCA–mutated patients, hazard ratio [HR] = 0.45; germline BRCA–mutated patients, HR = 0.27). During the SGO 2021 Annual Meeting, Dr. Matulonis presented updated results of secondary endpoints, including safety and exploratory long-term efficacy.
Secondary Endpoints
“The updated progression-free survival 2 data indicate that the benefit of niraparib extends beyond first progression in both the non–germline BRCA–mutated and the germline BRCA–mutated cohorts, with hazard ratios of 0.81 and 0.67, respectively,” said Dr. Matulonis.
With an average follow-up of 67 months, final overall survival analysis showed no difference in overall survival for non-germline BRCA–mutated patients receiving niraparib. However, patients with an underlying germline BRCA–mutated status trended towards improved survival on niraparib, with an increase in overall survival of 9.7 months.
“It’s important to note that analysis of overall survival analysis was limited,” cautioned Dr. Matulonis. “It was also challenged by the higher rate of subsequent PARP inhibitor use and crossover therapy for patients on placebo initially, as well as lost data.”
Adverse Events
Consistent with previously reported data, hematologic treatment-emergent adverse events primarily occurred within the first year of niraparib treatment. With appropriate dose modifications that usually occur in the first year, said Dr. Matulonis, hematologic toxicities—specifically thrombocytopenia, anemia, and neutropenia—decreased significantly in subsequent years. The incidence of grade ≥ 3 thrombocytopenia decreased from 33.8% to 2.8%, anemia decreased from 25.6% to 0.7%, and neutropenia decreased from 19.3% to 2.1% from year 1 to years 2 and 3.
At the time of the primary analysis, the incidence of myelodysplastic syndromes (MDS) or acute myeloid leukemia (AML) was 1.4% in the niraparib arm vs 1.1% in the placebo arm. With long-term follow up and administration of subsequent therapies, 3.5% of patients in the niraparib arm developed MDS or AML vs 1.7% in the placebo arm. Dr. Matulonis also reported a higher risk of MDS or AML in the germline BRCA–mutated group compared to the non-germline BRCA–mutated group for both the niraparib and placebo arms.
Disclosure: Dr. Matulonis has received consulting/advisory fees from Merck, Novartis, and NextCure.
