In a Chinese phase III study reported in JAMA Oncology, Li et al found that niraparib maintenance therapy given with an individualized starting dose improved progression-free survival vs placebo in newly diagnosed patients with advanced ovarian cancer.
Study Details
In the double-blind multicenter trial, 384 patients who had undergone primary or interval debulking surgery and who had responded to first-line platinum-based chemotherapy were randomly assigned 2:1 between June 2018 and November 2019 to receive maintenance niraparib (n = 255) or placebo (n = 129). The starting dose of niraparib was 200 mg/d in patients weighing up to 77 kg and/or with a platelet count of up to 150 ×103/μL and 300 mg/d in all other patients. Overall, the starting dose was 200 mg for 247 patients in the niraparib group and for 128 in the placebo group and 300 mg for 8 patients in the niraparib group and for 1 in the placebo group. Treatment was given in 28-day cycles for up to 36 months. The primary endpoint was progression-free survival on blinded independent central review in the intention-to-treat population.
Key Findings
At data cutoff in September 2021, median follow-up for progression-free survival was 27.5 months (interquartile range [IQR] = 24.7–30.4 months). Median progression-free survival was 24.8 months (95% confidence interval [CI] = 19.2 months to not estimable) in the niraparib group vs 8.3 months (95% CI = 7.3–11.1 months) in the placebo group (hazard ratio [HR] = 0.45, 95% CI = 0.34–0.60, P < .001).
The niraparib group had significantly better median progression-free survival among patients with (not reached vs 10.8 months, HR = 0.40, 95% CI = 0.23–0.68) and without (19.3 vs 8.3 months, HR = 0.48, 95% CI = 0.34–0.67) germline BRCA variants; among patients with homologous recombination–deficient tumors (not reached vs 11.0 months; HR = 0.48, 95% CI = 0.34–0.68) and those with homologous recombination–proficient tumors (16.6 vs 5.5 months; HR = 0.41, 95% CI = 0.22–0.75); and among patients with optimal debulking (24.8 vs 8.3 months; HR = 0.44, 95% CI = 0.32–0.61) and those with suboptimal debulking (16.5 vs 8.3 months; HR = 0.27, 95% CI = 0.10–0.72).
Grade ≥ 3 adverse events occurred in 54.5% of patients in the niraparib group vs 17.8% of those in the placebo group; the most common adverse events in the niraparib group were anemia (18.0%), decreased neutrophils (17.3%), and decreased platelets (14.1%). Serious adverse events occurred in 18.8% vs 8.5% of patients, respectively. Adverse events led to treatment discontinuation in 6.7% vs 5.4% of patients. In the niraparib group, one patient developed acute myeloid leukemia, which resulted in death, and another developed myelodysplastic syndrome.
The investigators concluded: “This randomized clinical trial found that niraparib maintenance therapy prolonged progression-free survival in patients with newly diagnosed advanced ovarian cancer regardless of postoperative residual disease or biomarker status. The individualized starting dose was effective and safe in the first-line maintenance setting.”
Lingying Wu, MD, PhD, of the Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, is the corresponding author of the JAMA Oncology article.
Disclosure: The study was funded by Zai Lab (Shanghai) Co, Ltd, and the National Major Scientific and Technological Special Project for Significant New Drugs Development. For full disclosures of the study authors, visit jamanetwork.com.
