Updated data from the Phase III ENGOT-OV16/NOVA study revealed no significant overall survival (OS) benefit among recurrent ovarian cancer patients who underwent maintenance niraparib compared with those who received placebo. These findings were presented during the 2023 Society of Gynecologic Oncology (SGO) 54th Annual Meeting on Women's Cancer.
"In the previously published primary analysis, niraparib maintenance therapy significantly prolonged progression-free survival regardless of germline BRCA-mutated or HRD biomarker status with a median follow-up of 16.9 months (N Engl J Med 2016; doi: 10.1056/NEJMoa1611310)," noted Ursula Matulonis, MD, Chief of the Division of Gynecologic Oncology at Dana-Farber Cancer Institute.
"The objectives of this updated analysis were to report the final updated overall survival and long-term safety results from the Phase III NOVA study of niraparib maintenance therapy in patients with platinum-sensitive recurrent ovarian cancer," said Matulonis, while noting that the pre-planned OS analysis for NOVA was presented previously at SGO 2021, but was associated with missing data on survival status and post-progression therapies.
"After the mature (>60%) OS analysis was presented to the FDA, the agency recommended retrieval of further survival data and post-progression treatment data," she explained. "Data retrieval efforts reduced missing survival status from 17 percent to approximately 2 percent and the data cutoff was extended by 6 months up to the date of study unblinding."
Study Details
As a randomized, double-blind, placebo-controlled, Phase III trial, NOVA included patients with platinum-sensitive recurrent ovarian cancer who were enrolled into independent germline BRCA (gBRCAm) and non-gBRCA cohorts. A total of 553 patients were then randomized 2:1 to receive niraparib 300 mg once daily or placebo. The primary endpoint of the study was progression-free survival, which was assessed by a blinded independent central review. OS was a secondary endpoint.
In this updated analysis, the study investigators completed a vital status procedure to retrieve the last known alive status for 92 patients with missing survival data with a data cutoff of March 31, 2021. This comprehensive effort included outreach to 24 sites across 13 countries, according to Matulonis. "Final overall survival was evaluated in both cohorts and also in the non-gBRCAm cohort by HRD status as exploratory analyses," she noted.
The median follow-up at data cutoff (March 31, 2021) was more than 75 months across both cohorts and treatment arms. In this updated analysis, survival status is now available for 97.6 percent (540 of 553) of patients. Data showed an overall OS maturity of 77.9 percent. Among patients in the gBRCAm cohort, median OS was 40.9 months with niraparib and 38.1 months with placebo. The median OS in the non-gBRCAm group was 31 months and 34.8 months with and without niraparib, respectively. The differences in OS between treatment arms were not interpreted to be significant in either cohort, according to Matulonis.
"In the homologous recombination deficient subgroup, median overall survival was 35.6 months with niraparib versus 41.4 months with placebo," she noted during her presentation. "In the homologous recombination proficient subgroup, median OS was 27.9 months with both niraparib and placebo.
"In homologous recombination not determined subgroup, median overall survival was 29.8 months with niraparib versus 20.2 months with placebo," she continued. "The differences in overall survival between treatment arms were not interpreted to be significant in any of the exploratory HRD subgroups."
Additional secondary endpoints-chemotherapy-free interval, time to first subsequent therapy, PFS2, and time to second subsequent therapy-demonstrated a persistent treatment effect numerically in favor of niraparib versus placebo and in both the gBRCAm and non-gBRCAm cohorts, Matulonis reported.
"While the additional data captured survival outcomes for the overwhelming majority of patients, data on subsequent therapies were not available in many cases," she noted. "There remains a considerable amount of missing data for these measures, as well as imbalances in post-progression therapy."
While discussing safety findings, Matulonis noted that no new safety signals were observed with long-term follow-up. The safety profile for niraparib was consistent with that seen in previous data readouts.
"As of March 31, 2021, 3.8 percent of patients who received niraparib and 1.7 percent of patients who received placebo developed myelodysplastic syndrome or acute myeloid leukemia (MDS/AML)," according to Matulonis and colleagues. "The risk of MDS/AML was highest in the gBRCAm patients treated with a PARP inhibitor and was 7.4 percent, consistent with other Phase III studies in the recurrent platinum-sensitive setting."
Conclusions
The findings from this updated analysis underscore the importance of long-term patient follow-up, as well as the need for continued research.
"Our patients with ovarian cancer are living longer and are thus receiving more therapies," concluded Matulonis, in a statement. "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."
Catlin Nalley is a contributing writer.