The overall survival hazard ratio numerically favored niraparib in the germline BRCA mutation cohort and favored placebo in the non-germline BRCA mutation cohort in patients with platinum-sensitive recurrent ovarian cancer.
Data from the ENGOT-OV16/NOVA study show no difference in overall survival (OS) for patients with platinum-sensitive recurrent ovarian cancer who received poly (ADP-ribose) polymerase (PARP) inhibitor niraparib maintenance therapy and those who did not.
ENGOT-OV16/NOVA was a randomized, double-blind, placebo-controlled, phase 3 trial with 553 total patients with platinum-sensitive recurrent ovarian cancer. Participants were enrolled into independent germline BRCA and non-germline BRCA cohorts, then randomized 2:1 to receive niraparib 300 mg once daily or placebo. Results from the trial were presented at the Society of Gynecologic Oncology (SGO) 2023 Annual Meeting on Women’s Cancer.
Primary results from the study were released in 2016 and suggested a progression-free survival benefit for the niraparib arm compared to the placebo arm. The initial OS analysis was presented at the 2021 SGO annual meeting, but the survival analysis, a secondary endpoint, was limited by missing follow-up survival data on 92 patients.
Survival status is now available for 97.6% of patients in the updated analysis. However, the authors noted that survival data are challenging to interpret.
“There are imbalances in post-progression therapy in the different groups, and missing data still exists on these post-progression therapies,” said presenter Ursula Matulonis, MD, of the Dana-Farber Cancer Institute, in a press release. “And, the study was not powered for formal overall survival analyses, creating additional interpretation challenges.”
Once the missing data were resolved, the survival differences between the niraparib and placebo arms were not interpreted to be significant in either cohort, although the OS hazard ratio numerically favored niraparib in the germline BRCA mutation cohort and favored placebo in the non-germline BRCA mutation cohort.
Additionally, no new safety signals were observed with long-term follow-up. As of the March 31, 2021, data cutoff, 3.8% of those who received niraparib and 1.7% of those who received placebo developed myelodysplastic syndrome (MDS) or acute myeloid leukemia (AML). The risk of MDS or AML was highest in the germline BRCA mutation patients treated with a PARP inhibitor and was 7.4%, consistent with other phase 3 studies in the recurrent platinum-sensitive setting.
The results of the trial underscore the importance of long-term follow-up of patients and point to a continued need for research, according to the authors.
“Our patients with ovarian cancer are living longer and are thus receiving more therapies,” Matulonis said in the press release. “It is critical for trials to follow patients long-term for overall survival after they stop study treatment and to carefully record and chronicle post-study treatment therapies. Understanding the impact of PARP inhibitor therapy on post-progression treatment resistance is also an important area of research.”
Trial’s Long-Term Follow-Up Data Shows No Difference in Overall Survival Among Ovarian Cancer Patients Who Did and Did Not Receive PARP Inhibitor Maintenance Therapy. News release. Society of Gynecologic Oncology. March 26, 2023. Accessed April 6, 2023.