Niraparib maintenance therapy in patients with platinum-sensitive recurrent ovarian cancer using an individualized starting dose (NORA): a randomized, double-blind, placebo-controlled phase III trial☆

X H Wu; J Q Zhu; R T Yin; J X Yang; J H Liu; J Wang; L Y Wu; Z L Liu; Y N Gao; D B Wang; G Lou; H Y Yang; Q Zhou; B H Kong; Y Huang; L P Chen; G L Li; R F An; K Wang; Y Zhang; X J Yan; X Lu; W G Lu; M Hao; L Wang; H Cui; Q H Chen; G Abulizi; X H Huang; X F Tian; H Wen; C Zhang; J M Hou; M R Mirza

doi:10.1016/j.annonc.2020.12.018

Niraparib maintenance therapy in patients with platinum-sensitive recurrent ovarian cancer using an individualized starting dose (NORA): a randomized, double-blind, placebo-controlled phase III trial^☆

Ann Oncol. 2021 Apr;32(4):512-521. doi: 10.1016/j.annonc.2020.12.018. Epub 2021 Jan 14.

Authors

X H Wu¹, J Q Zhu², R T Yin³, J X Yang⁴, J H Liu⁵, J Wang⁶, L Y Wu⁷, Z L Liu⁸, Y N Gao⁹, D B Wang¹⁰, G Lou¹¹, H Y Yang¹², Q Zhou¹³, B H Kong¹⁴, Y Huang¹⁵, L P Chen¹⁶, G L Li¹⁷, R F An¹⁸, K Wang¹⁹, Y Zhang²⁰, X J Yan²¹, X Lu²², W G Lu²³, M Hao²⁴, L Wang²⁵, H Cui²⁶, Q H Chen²⁷, G Abulizi²⁸, X H Huang²⁹, X F Tian³⁰, H Wen³¹, C Zhang³², J M Hou³², M R Mirza³³

Affiliations

¹ Department of Gynecologic Oncology, Fudan University Shanghai Cancer Center, Shanghai, China. Electronic address: wu.xh@fudan.edu.cn.
² Department of Gynecologic Oncology, Cancer Hospital of the University of Chinese Academy of Sciences (Zhejiang Cancer Hospital), Hangzhou, China.
³ Department of Obstetrics and Gynecology, Key Laboratory of Birth Defects and Related Diseases of Women and Children, Ministry of Education, West China Second University Hospital, Sichuan University, Chengdu, China.
⁴ Department of Gynecologic Oncology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
⁵ Department of Gynecologic Oncology, Sun Yat-sen University Cancer Center, Guangzhou, China.
⁶ Department of Gynecologic Oncology, Hunan Cancer Hospital, The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, China.
⁷ Department of Gynecologic Oncology, National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
⁸ Department of Oncology, The First Hospital of Jilin University, Changchun, China.
⁹ Department of Gynecology, Peking University Cancer Hospital & Institute, Beijing, China.
¹⁰ Department of Gynecology, Cancer Hospital of China Medical University, Liaoning Cancer Hospital & Institute, Shenyang, China.
¹¹ Department of Gynecology Oncology, Harbin Medical University Cancer Hospital, Harbin, China.
¹² Department of Gynecologic Oncology, The Third Affiliated Hospital of Kunming Medical University/Yunnan Cancer Hospital, Kunming, China.
¹³ Gynecological Oncology Center, Chongqing University Cancer Hospital, Chongqing, China.
¹⁴ Department of Obstetrics and Gynecology, Qilu Hospital of Shandong University, Ji'nan, China.
¹⁵ Department of Gynecologic Oncology, Hubei Cancer Hospital, Wuhan, China.
¹⁶ Department of Gynecological Oncology, Affiliated Cancer Hospital of Guangzhou Medical University, Guangzhou, China.
¹⁷ Cancer Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
¹⁸ Department of Obstetrics and Gynecology, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China.
¹⁹ Department of Gynecologic Oncology, Tianjin Medical University Cancer Institute and Hospital, Tianjin, China.
²⁰ Department of Obstetrics and Gynecology, Xiangya Hospital, Central South University, Changsha, China.
²¹ Department of Gynecology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China.
²² Department of Gynecology Oncology, Obstetrics & Gynecology Hospital of Fudan University, Shanghai, China.
²³ Department of Obstetrics and Gynecology, Women's Hospital, School of Medicine, Zhejiang University, Hangzhou, China.
²⁴ Department of Obstetrics and Gynecology, The Second Hospital of Shanxi Medical University, Taiyuan, China.
²⁵ Department of Gynecological Oncology, Affiliated Cancer Hospital of Zhengzhou University, Henan Cancer Hospital, Zhengzhou, China.
²⁶ Department of Obstetrics and Gynecology, Center of Gynecologic Oncology, Peking University People's Hospital, Beijing, China.
²⁷ Department of Gynecology, The First Affiliated Hospital of Xiamen University, Xiamen, China.
²⁸ Department of Gynecology, The Affiliated Cancer Hospital of Xinjiang Medical University, Urumqi, China.
²⁹ Department of Obstetrics and Gynecology, The Second Hospital of Hebei Medical University, Shijiazhuang, China.
³⁰ Department of Gynecology Oncology, Shaanxi Provincial Cancer Hospital, Xi'an, China.
³¹ Department of Gynecologic Oncology, Fudan University Shanghai Cancer Center, Shanghai, China.
³² R&D Department, Zai Lab (Shanghai) Co., Ltd, Shanghai, China.
³³ Department of Oncology, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark.

PMID: 33453391
DOI: 10.1016/j.annonc.2020.12.018

Abstract

Background: This study evaluated maintenance treatment with niraparib, a potent inhibitor of poly(ADP-ribose) polymerase 1/2, in patients with platinum-sensitive recurrent ovarian cancer.

Patients and methods: In this phase III, double-blind, placebo-controlled study conducted at 30 centers in China, adults with platinum-sensitive recurrent ovarian cancer who had responded to their most recent platinum-containing chemotherapy were randomized 2 : 1 to receive oral niraparib (300 mg/day) or matched placebo until disease progression or unacceptable toxicity (NCT03705156). Following a protocol amendment, patients with a bodyweight <77 kg or a platelet count <150 × 10³/μl received 200 mg/day, and all other patients 300 mg/day, as an individualized starting dose (ISD). Randomization was carried out by an interactive web response system and stratified by BRCA mutation, time to recurrence following penultimate chemotherapy, and response to most recent chemotherapy. The primary endpoint was progression-free survival (PFS) assessed by blinded independent central review.

Results: Between 26 September 2017 and 2 February 2019, 265 patients were randomized to receive niraparib (n = 177) or placebo (n = 88); 249 patients received an ISD (300 mg, n = 14; 200 mg, n = 235) as per protocol. In the intention-to-treat population, median PFS was significantly longer for patients receiving niraparib versus placebo: 18.3 [95% confidence interval (CI), 10.9-not evaluable] versus 5.4 (95% CI, 3.7-5.7) months [hazard ratio (HR) = 0.32; 95% CI, 0.23-0.45; P < 0.0001], and a similar PFS benefit was observed in patients receiving an ISD, regardless of BRCA mutation status. Grade ≥3 treatment-emergent adverse events occurred in 50.8% and 19.3% of patients who received niraparib and placebo, respectively; the most common events were neutrophil count decreased (20.3% versus 8.0%) and anemia (14.7% versus 2.3%).

Conclusions: Niraparib maintenance treatment reduced the risk of disease progression or death by 68% and prolonged PFS compared to placebo in patients with platinum-sensitive recurrent ovarian cancer. Individualized niraparib dosing is effective and safe and should be considered standard practice in this setting.

Keywords: maintenance therapy; niraparib; ovarian cancer.

Publication types

Clinical Trial, Phase III
Randomized Controlled Trial
Research Support, Non-U.S. Gov't

MeSH terms

Adult
Antineoplastic Combined Chemotherapy Protocols
China
Double-Blind Method
Female
Humans
Indazoles
Maintenance Chemotherapy
Neoplasm Recurrence, Local / drug therapy
Ovarian Neoplasms* / drug therapy
Ovarian Neoplasms* / genetics
Piperidines
Poly(ADP-ribose) Polymerase Inhibitors* / adverse effects

Substances

Indazoles
Piperidines
Poly(ADP-ribose) Polymerase Inhibitors
niraparib

Associated data

ClinicalTrials.gov/NCT03705156