Researchers have found no significant differences in overall survival between patients with platinum-sensitive recurrent ovarian cancer who received maintenance therapy with the poly (ADP-ribose) polymerase (PARP) inhibitor niraparib or placebo, according to new findings presented by Matulonis et al at the Society of Gynecologic Oncology (SGO) 2023 Annual Meeting on Women’s Cancer.
Results From the 2016 Study
Primary results from the study—published in 2016 by Mirza et al in The New England Journal of Medicine—indicated that patients had a higher rate of progression-free survival when receiving niraparib maintenance therapy compared with placebo. However, the secondary endpoint was limited by missing follow-up data on overall survival for 92 patients. For the updated analysis, the researchers reported that survival data are now available for 97.6% of patients.
“There are imbalances in postprogression therapy in the different groups, and missing data still exist on these postprogression therapies,” explained Ursula Matulonis, MD, Professor of Medicine at Harvard Medical School, Chief of the Division of Gynecologic Oncology and the Brock-Wilson Family Chair at the Dana-Farber Cancer Institute, and Co-Leader of the Gynecologic Cancer Program at the Dana-Farber/Harvard Cancer Center. “And the study was not powered for formal overall survival analyses, creating additional interpretation challenges,” she added.
Study Methods and Results
In the new randomized, double-blind, placebo-controlled, phase III ENGOT-OV16/NOVA trial (ClinicalTrials.gov identifier NCT01847274), the researchers enrolled 553 patients with platinum-sensitive recurrent ovarian cancer into independent cohorts based on the presence (gBRCA) or absence (non-gBRCA)of a germline BRCA mutation, then randomly assigned the patients at a ratio of two to one to receive 300 mg of niraparib or placebo once daily. Once data from the 2016 study were resolved, the survival differences between patients who received niraparib maintenance therapy and placebo were not interpreted to be significant, though the overall survival hazard ratio numerically favored niraparib maintenance therapy among patients in the gBRCA cohort and favored placebo in the non-gBRCA cohort.
No new safety signals were observed with long-term follow-up. As of the March 31, 2021, data cutoff, 3.8% of the patients who received niraparib maintenance therapy and 1.7% of those who received placebo developed myelodysplastic syndrome or acute myeloid leukemia. Patients in the gBRCA cohort who were treated with niraparib maintenance therapy had a 7.4% risk of developing these diseases—the highest of any cohort—consistent with other phase III studies involving patients with platinum-sensitive recurrent malignancies.
Conclusions
The results of the trial underscored the importance of long-term follow-up for patients with ovarian cancer and highlighted the need for additional research.
“Our patients with ovarian cancer are living longer and are thus receiving more therapies,” noted Dr. Matulonis. “It is critical for trials to follow patients long-term for overall survival after they stop study treatment and to carefully record and chronicle poststudy treatment therapies. Understanding the impact of PARP inhibitors on postprogression treatment resistance is also an important area of research,” she concluded.
Disclosure: For full disclosures of the study authors, visit nejm.org.
