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.1
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.
Ursula A. Matulonis, MD
Based on adjusted analyses, a trend toward 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.
Finally, a 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,2 niraparib demonstrated a statistically significant improvement in progression-free survival regardless of germline status (patients with non-germline BRCA–mutated disease, hazard ratio [HR] = 0.45; patients with germline BRCA–mutated disease, HR = 0.27). During the SGO 2021 meeting, Dr. Matulonis presented updated results of secondary endpoints, including safety and exploratory long-term efficacy.
“The updated progression-free survival 2 data indicate that the benefit of niraparib extends beyond first disease 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, a final overall survival analysis showed no difference in overall survival for patients with non-germline BRCA–mutated disease receiving niraparib. However, patients with an underlying germline BRCA–mutated status trended toward improved survival on niraparib, with an increase in overall survival of 9.7 months.
“It’s important to note that analysis of overall survival 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 with the non-germline BRCA–mutated group for both the niraparib and placebo arms.
DISCLOSURE: Dr. Matulonis has received honoraria from Advaxis; has served as a consultant or advisor to Merck, NextCure, and Novartis; has received research funding from Fujifilm, ImmunoGen, Leap Therapeutics, Merck, Mersana, Novartis, SQZ Biotechnologies, Syndax, and Tesaro; and has been reimbursed for travel, accommodations, or other expenses by AstraZeneca.
References
1. Matulonis U: Long-term safety and secondary efficacy endpoints in the ENGOT-OV16/NOVA phase III trial of niraparib in recurrent ovarian cancer. Society of Gynecologic Oncology 2021 Virtual Annual Meeting on Women’s Cancer. Abstract 11139. Presented March 19, 2021.
2. Mirza MR, Monk BJ, Herrstedt J, et al: Niraparib maintenance therapy in platinum-sensitive, recurrent ovarian cancer. N Engl J Med 375:2154-2164, 2016.
