The PRIME (NCT03709316) study was a randomized, double-blind, placebo-controlled, phase 3 trial. Eligible patients were randomised (2:1) to receive niraparib or placebo. Niraparib maintenance therapy with an individualized starting dose (ISD) improved PFS vs placebo (HR 0.45; 95% CI, 0.34–0.60) in Chinese patients with newly diagnosed, advanced ovarian cancer and CR or PR to 1L platinum-based chemotherapy. This post-hoc analysis aims to evaluate niraparib efficacy by the timing of debulking surgery and postoperative residual disease status.
This analysis reports PFS and HRs based on surgical timing (primary debulking surgery [PDS] and interval debulking surgery [IDS]) and residual disease status [optimal(R0/R1) vs suboptimal(R2)]. Median PFS (assessed by BICR) and HRs were obtained using the Kaplan-Meier method and stratified Cox proportional hazards models, respectively.
The DCO date was 30 Sep. 2021. In total, 255 patients were randomized and treated to niraparib (134 PDS, 121 IDS) and 129 to placebo (70 PDS, 59 IDS). The PFS median follow-up was 27.5 months. The efficacy results are shown in Table 1. Niraparib significantly prolonged PFS compared with placebo irrespective of surgical timing. For PFS, HR 0.63 (95% CI 0.42–0.94, median PFS was not reached in niraparib arm vs. 12.0 months in placebo arm) in patients who underwent PDS; HR = 0.32 (95% CI 0.21-0.48, median PFS in niraparib and placebo arm was 22.3 vs. 5.6 months) in patients undergoing IDS. In niraparib-treated patients, those who underwent PDS and IDS experienced similar rates of grade ≥3 adverse events (TEAEs) (50.7% vs 58.7%) and treatment discontinuation due to AEs (6.7% vs 6.6%).
| Table 1. Efficacy of niraparib maintenance therapy in patients with newly diagnosed advanced ovarian cancer by surgical timing and residual disease status | |||||
| Subgroups | Niraparib | Placebo | Hazard ratio (95% CI) | ||
| n | mPFS, months | n | mPFS, months | ||
| Overall | 255 | 24.8 | 129 | 8.3 | 0.45 (0.34–0.60) |
| PDS | 134 | NR | 70 | 12.0 | 0.63 (0.42–0.94) |
| Optimal | 101 | NR | 56 | 13.8 | 0.74 (0.46–1.17) |
| Suboptimal | 24 | 13.8 | 11 | 8.3 | 0.28 (0.10–0.84) |
| IDS | 121 | 22.3 | 59 | 5.6 | 0.32 (0.21–0.48) |
| Optimal | 92 | 24.7 | 49 | 5.6 | 0.26 (0.17–0.41) |
| Suboptimal | 12 | 16.5 | 3 | 5.5 | 0.20 (0.02–2.22) |
| CI: confidence interval; IDS: interval debulking surgery; mPFS: median progression-free survival; PDS: primary debulking surgery; NR: not reached. | |||||
This subgroup analysis demonstrated that niraparib improved PFS regardless of surgical timing compared with placebo in patients with newly diagnosed advanced ovarian cancer.
Clinical trial identifier: NCT03709316