35O - Overall Survival of Niraparib with Individualized Starting Dose as Maintenance Therapy in Patients with Platinum-Sensitive Recurrent Ovarian Cancer Adjusted for Subsequent PARPi Use in Placebo Group: Results from an Ad Hoc Interim Analysis for the Phase 3 NORA Study

Background

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.

Methods

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.

Results

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 the table. 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: 35O

OS summary for ITT population and by gBRCA status

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.

Conclusions

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.

Legal entity responsible for the study

Zai Lab.

Funding

This work was supported by Zai Lab (No grant number). The work was also partially supported by the National Major Scientific and Technological Special Project for ‘Significant New Drugs Development’ in 2018, China [grant number 2018ZX09736019].

Disclosure

X. Zhen: Financial Interests, Personal, Full or part-time Employment: Zai Lab (US) LLC; Financial Interests, Personal, Stocks/Shares: Zai Lab (US) LLC. J. Dong: Financial Interests, Personal, Full or part-time Employment: Zai Lab (Shanghai) Co., Ltd; Financial Interests, Personal, Stocks/Shares: Zai Lab (Shanghai) Co., Ltd. C. Zhang: Financial Interests, Personal, Full or part-time Employment: Zai Lab (Shanghai) Co., Ltd; Financial Interests, Personal, Stocks/Shares: Zai Lab (Shanghai) Co., Ltd. J. Hou: Financial Interests, Personal, Full or part-time Employment: Zai Lab (Shanghai) Co., Ltd; Financial Interests, Personal, Stocks/Shares: Zai Lab (Shanghai) Co., Ltd. M.R. Mirza: Financial Interests, Personal, Advisory Board: AstraZeneca, Biocad, GSK, Karyopharm, Merck, Roche, Zai Lab; Financial Interests, Personal, Invited Speaker: AstraZeneca, GSK, Karyopharm; Financial Interests, Personal, Stocks/Shares: Karyopharm; Financial Interests, Institutional, Research Grant: GSK, AstraZeneca, Ultimovacs, Apexigen; Financial Interests, Institutional, Invited Speaker: Deciphera; Non-Financial Interests, Personal, Advisory Role: Ultimovacs, Apexigen. All other authors have declared no conflicts of interest.