In randomized phase 3 NORA trial (NCT03705156), niraparib maintenance therapy with an individualized starting dose (ISD) significantly improved PFS (PFS; primary endpoint) and provided a favorable OS (OS; secondary endpoint) trend versus placebo, in patients with platinum-sensitive recurrent ovarian cancer (PSROC). Evaluating OS in randomized controlled trials can often be confounded by bias introduced by subsequent therapy. Considerable numbers of patients in placebo arm received subsequent PARPi therapy. This updated analysis aims to describe the treatment effect of niraparib versus placebo on OS adjusted for subsequent PAPPi use in placebo arm.
265 Chinese patients with PSROC who achieved a CR or PR to last platinum-based chemotherapy were randomized (2:1) to receive niraparib (n = 177) or placebo (n = 88). A majority of patients (249/265) received niraparib or placebo with an ISD based on baseline body weight and platelet count (200 mg for patients with baseline body weight < 77 kg or platelet count < 150,000/μL; otherwise, 300 mg). Kaplan-Meier method was used to describe OS. Hazard ratio was estimated using a Cox proportional model. Inverse probability of censoring weighting (IPCW) method was used to estimate the effect of niraparib versus placebo adjusted for subsequent PARPi use in placebo arm.
As of the data cut-off of Sep. 23, 2022, an ad hoc interim OS analysis was conducted at 44% (117/265) maturity. Detailed data are provided in Table 1. 43% (38/88) patients [54% (19/35) in gBRCAmut and 36% (19/53) in non-gBRCAmut] in the placebo group received subsequent PARPi therapy.
| Table 1: OS summary for ITT population and by gBRCA status | |||||||
| All | gBRCAmut | Non-gBRCAmut | |||||
| Niraparib N=177 | Placebo N=88 | Niraparib N=65 | Placebo N=35 | Niraparib N=112 | Placebo N=53 | ||
| ITT Analysis | mOS (mo) | 46.32 | 43.37 | NR | 47.61 | 43.10 | 38.41 |
| HR (95%CI) | 0.821 (0.558-1.207) | 0.764 (0.398-1.464) | 0.855 (0.529-1.381) | ||||
| Adjusted IPCW Analysis | TBU | ||||||
| ITT: intention to treat; gBRCAmut, germline BRCA mutation; HR, hazard ratio; CI: confidence interval; mOS: median overall survival; NR: not reached; TBU: to be updated. | |||||||
Consistent with the OS results from the ITT analysis, the IPCW analysis further demonstrates favorable OS trend and supports positive benefit-risk profile of niraparib with ISD as maintenance therapy for PSROC.