Niraparib (nir) showed a blinded independent central review–assessed PFS benefit as a first-line (1L) maintenance therapy (MT) in the primary analysis of PRIMA (data cut 17 May 2019) across biomarker subgroups, including a substantial benefit in patients (pts) with homologous recombination–deficient (HRd) tumours. These results were the basis for approval of nir as MT after response to 1L platinum-based chemotherapy (CT). Here we report investigator-assessed (IA) cPFS (the probability of remaining alive and progression free beyond a specified landmark) in PRIMA.
This double-blind, placebo (PBO)-controlled phase 3 trial evaluated nir in pts with newly diagnosed, advanced high-grade serous or endometrioid ovarian, primary peritoneal, or fallopian tube cancer (OC) at high risk for relapse after a complete or partial response (CR or PR) to 1L platinum-based CT. Stratification factors were best response to 1L CT regimen (CR/PR), receipt of neoadjuvant CT (yes/no), and homologous recombination deficiency status (HRd or HRp/HRnd) per the Myriad myChoice® CDx PLUS assay. Pts received nir or PBO once daily (2:1 ratio). IA cPFS was analysed for the HRd and intention-to-treat (ITT) populations, using the 17 Nov 2021 data cut.
The median follow-up time was 3.5 y. The estimated PFS rate at 4 y was 38% for nir-treated pts and 17% for PBO-treated pts in the HRd population and 24% (nir) vs 14% (PBO) in the ITT population. The 2-y cPFS probabilities beyond the 1- and 2-y landmarks were higher in the nir arm than in the PBO arm (HRd: 1 y: 62% vs 50%, 2 y: 74% vs 60%; ITT: 1 y: 54% vs 46%, 2 y: 67% vs 64%; Table).
Safety was previously reported (González-Martín, et al. Ann Oncol. 2022;33[suppl 7]:S789).
A durable PFS benefit (nir vs PBO) was observed up to 4 y after randomisation in the ITT and HRd populations, as determined by IA. Pts free from disease progression or death at the 2-y landmark had a high probability of remaining free from progression or death at 4 y, supporting the use of nir as a 1L MT.
| HRd | ||||
|---|---|---|---|---|
| Nir | PBO | |||
| Landmark time from randomization | Events/ total pts | 2-y probability from landmark, % (95% CI) | Events/ total pts | 2-y probability from landmark, % (95% CI) |
| 0 | 137/247 | 51 (44–57) | 98/126 | 29 (21–37) |
| 1 y | 69/159 | 62 (54–70) | 33/57 | 50 (36–62) |
| 2 y | 26/110 | 74 (64–82) | 11/34 | 60a |
| ITT | ||||
| Nir | PBO | |||
| Landmark time from randomization | Events/ total pts | 2-y probability from landmark, % (95% CI) | Events/ total pts | 2-y probability from landmark, % (95% CI) |
| 0 | 332/487 | 36 (31–40) | 199/246 | 22 (17–28) |
| 1 y | 124/244 | 54 (47–60) | 54/92 | 46 (36–56) |
| 2 y | 42/152 | 67 (57–76) | 15/51 | 64a |
| a95% CI were not calculated at time points with <10 pts. | ||||
NCT02655016
Writing and editorial support, funded by GSK (Waltham, MA, USA) and coordinated by Pru Roaf of GSK, was provided by Betsy C. Taylor, PhD, CMPP, Tafara T.R. Kunota, PhD, and Dena McWain of Ashfield MedComms, an Inizio company (Middletown, CT, USA).