Chinese patients with platinum-sensitive recurrent ovarian cancer (PSROC) receiving a starting dose of niraparib that was individualised according to each patient’s baseline body weight and platelet count demonstrated prolonged median progression-free survival (mPFS) compared to patients receiving placebo. These findings were from a subgroup analysis of the phase III NORA study presented at the ESMO Asia Virtual Congress 2020, held from 20 to 22 November 2020.
According to Jianqing Zhu of the Department of Gynaecologic Oncology, Cancer Hospital of the University of Chinese Academy of Sciences (Zhejiang Cancer Hospital) in Hangzhou, China, niraparib maintenance therapy with individualised dosing significantly improved the outcome of Chinese patients with PSROC.It is consistent with the intent-to-treat (ITT) population in NORA.
Professor Zhu presented findings from NORA, which was conducted in 32 hospitals throughout China. The study enrolled women aged ≥18 years with PSROC and either high-grade serous histologic or germline BRCA mutation features, who achieved a complete or partial response after completion of the last round of platinum therapy.
In the double-blinded, randomised, placebo-controlled phase III NORA (NCT03705156) study, following 2:1 randomisation patients were treated with oral niraparib at 300 mg once daily or placebo. After first 16 patients were treated with the fixed starting dose of 300 mg once daily, the protocol was amended to adopt an individualised starting dosing regimen according to the baseline body weight and platelet count; that is 300 mg once daily for patients with baseline body weight ≥77kg and platelet count ≥150×103/μL and for all other patients 200 mg once daily as the starting dose.
The primary endpoint was PFS assessed by blinded independent central review.
mPFS was more than tripled with niraparib over placebo
Among the 265 randomised patients in the ITT population, the majority of patients (94% [249/265], ITT population) received individualised starting dose. The individualised starting dose subgroup patients had median body weight of 61 kg, and most patients (n=235) received niraparib 200 mg or matched placebo, the minority of patient (n=14) met criteria of receiving 300mg once daily as starting dose.
With individualised dosing, patients treated with niraparib had significantly longer mPFS of 18.3 months than that of 5.4 months observed in the placebo group (hazard ratio [HR] 0.30; 95% confidence interval [CI] 0.21–0.43).
Median progression-free survival in the NORA study.
© Jianqing Zhu.
Regarding the safety anlysis, with niraparib versus placebo the incidence of grade ≥3 treatment emergent adverse events (Aes) was 48.8% versus 20.5%, and the incidences of ≥3 grade haematological AEs of decreased neutrophil count were 20.5% versus 8.4%, decreased platelet count 9.6% versus 1.2%, and anaemia 13.9% versus 2.4%, respectively.
Conclusions
According to the authors this is the first randomised, placebo-controlled phase III study to demonstrate the efficacy and safety of niraparib in Chinese patients with platinum-sensitive recurrent ovarian cancer.
They noted that an individualised starting dose of niraparib is effective and well tolerated. Furthermore, they advised that it should be considered standard clinical practice in this patient population.
This study was funded by Zai Lab and partially supported by the Chinese National Major Scientific and Technological Special Project for “Significant New Drugs Development” and Shanghai Municipal Commission of Economy and Infomatization.
Reference
235O – Wu X, Zhu J, Yin R, et al. Efficacy and safety of Niraparib in Chinese Patients with Platinum-Sensitive Recurrent Ovarian Cancer (NORA) with Individualized Starting Dose: A Subgroup Analysis of A Randomized, Double-Blind, Placebo-Controlled, Phase 3 Trial. ESMO Asia Virtual Congress 2020 (20-22 November).