ENGOT-OV16/NOVA trial of niraparib in recurrent ovarian cancer: Survival and long-term safety

IF 4.5 2区 医学 Q1 OBSTETRICS & GYNECOLOGY
Ursula A. Matulonis , Jørn Herrstedt , Amit Oza , Sven Mahner , Andrés Redondo , Dominique Berton , Jonathan S. Berek , Charlotte A. Haslund , Frederik Marmé , Antonio González-Martín , Stéphanie Bécourt , Anna V. Tinker , Jonathan A. Ledermann , Benedict Benigno , Gabriel Lindahl , Nicoletta Colombo , Izabela A. Malinowska , Wenlei Liu , Manjinder Bains , Bradley J. Monk , Mansoor R. Mirza
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引用次数: 0

Abstract

Objective

To evaluate secondary efficacy endpoints and safety for the ENGOT-OV16/NOVA (NCT01847274) trial of niraparib maintenance therapy after extended follow-up and vital-status-data retrieval. Previously reported analyses (data cutoff, October 1, 2020) indicated benefit of niraparib maintenance therapy beyond first progression, but overall survival (OS) analyses were limited by missing data.

Methods

Patients were randomized 2:1 to niraparib (300 mg once daily) or placebo. A vital status check was extended to retrieve last-known-alive status for patients with missing survival data. Prespecified secondary efficacy outcomes (OS, chemotherapy-free interval [CFI], time to first subsequent therapy [TFST], PFS2, time to second subsequent therapy [TSST]) and safety are reported based on the extended data cutoff (March 31, 2021).

Results

Survival status was available for 97.6% (540/553) of randomized patients (germline BRCA [gBRCA]-mutated, 203; non-gBRCA–mutated, 350). Median OS with niraparib and placebo was 40.9 and 38.1 months, respectively, in the gBRCA-mutated cohort (hazard ratio [HR], 0.85; 95% confidence interval [CI], 0.61–1.20) and 31.0 and 34.8 months, respectively, in the non-gBRCA–mutated cohort (HR, 1.06; 95% CI, 0.81–1.37). Medians for CFI, TFST, PFS2, and TSST numerically favored niraparib in both cohorts. No new safety signals were detected.

Conclusions

OS did not significantly differ between treatment arms. Prespecified secondary efficacy endpoints numerically favored niraparib. Long-term safety remained consistent with the established niraparib safety profile. Taken together with the significant improvements in PFS observed in the primary analysis, these data support a favorable overall benefit–risk profile for niraparib in the recurrent OC maintenance setting.
尼拉帕利治疗复发性卵巢癌的ENGOT-OV16/NOVA试验:生存期和长期安全性
目的评价ENGOT-OV16/NOVA (NCT01847274)试验在延长随访和生命状态数据检索后尼拉帕尼维持治疗的次要疗效终点和安全性。先前报道的分析(数据截止日期为2020年10月1日)表明,尼拉帕尼维持治疗的益处超过了首次进展,但总生存期(OS)分析受到数据缺失的限制。方法将患者按2:1随机分为尼拉帕尼组(300 mg每日1次)或安慰剂组。生命状态检查扩展到检索缺少生存数据的患者的最后已知生存状态。预先指定的次要疗效指标(OS、无化疗间隔时间(CFI)、到第一次后续治疗时间(TFST)、PFS2、到第二次后续治疗时间(TSST))和安全性基于扩展数据截止日期(2021年3月31日)进行报告。结果97.6%(540/553)的随机患者获得生存状态(种系BRCA [gBRCA]突变,203;non-gBRCA-mutated, 350)。在gbrca突变的队列中,尼拉帕尼和安慰剂的中位生存期分别为40.9和38.1 个月(风险比[HR], 0.85;95%可信区间[CI], 0.61-1.20),非gbrca突变队列分别为31.0和34.8 个月(HR, 1.06;95% ci, 0.81-1.37)。在两个队列中,CFI、TFST、PFS2和TSST的中位数在数值上都倾向于尼拉帕尼。没有检测到新的安全信号。结论各治疗组间sos无显著性差异。预先指定的次要疗效终点在数值上有利于尼拉帕尼。长期安全性与既定的尼拉帕尼安全性保持一致。结合在初步分析中观察到的PFS的显著改善,这些数据支持尼拉帕尼在复发性OC维持环境中有利的总体收益-风险特征。
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来源期刊
Gynecologic oncology
Gynecologic oncology 医学-妇产科学
CiteScore
8.60
自引率
6.40%
发文量
1062
审稿时长
37 days
期刊介绍: Gynecologic Oncology, an international journal, is devoted to the publication of clinical and investigative articles that concern tumors of the female reproductive tract. Investigations relating to the etiology, diagnosis, and treatment of female cancers, as well as research from any of the disciplines related to this field of interest, are published. Research Areas Include: • Cell and molecular biology • Chemotherapy • Cytology • Endocrinology • Epidemiology • Genetics • Gynecologic surgery • Immunology • Pathology • Radiotherapy
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