Efficacy and safety of niraparib as maintenance treatment in patients with newly diagnosed advanced ovarian cancer using an individualized starting dose (PRIME Study): A randomized, double-blind, placebo-controlled, phase 3 trial (LBA 5)

Li, Ning; Zhu, Jianqing; Yin, Rutie; Wang, Jing; Pan, Lingya; Kong, B.; Zheng, Hong; Liu, Jihong; Wu, Xiaohua; Wang, Li; Huang, Yi; Wang, Ke; Zou, Dongling; Zhao, Hongqin; Wang, Chunyan; Li, Weiguo; An, L.; Lou, Ge; Li, Guiling; Qu, Pengpeng; Yang, Hyejin; Zhen, Xiaoa; Hang, Wenzhao; Hou, Jianmei; Wu, Lingying

doi:10.1016/s0090-8258(22)01298-7

Cited by 41 publications

(67 citation statements)

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“…Niraparib efficacy was recently confirmed in PRIME trial comparing niraparib maintenance therapy with placebo in a larger population of patients with advanced serous or endometroid high grade ovarian cancer patients that responded to the chemotherapy with platinum. In this study niraparib maintenance significantly prolonged the PFS for the whole population regardless of BRCA status or cytoreductive surgery outcome (24.8 months with niraparib vs. 8.3 months with placebo; p < 0.001) [16].…”

Section: Clinical Efficacy Of Niraparibmentioning

confidence: 53%

Niraparib maintenance in newly diagnosed advanced ovarian cancer — review and case series

Tyszka

Stec

2023

Oncol Clin Pract

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Introducing PARP inhibitors maintenance therapy into clinical practice significantly improved treatment outcomes in patients with high-grade platinum-sensitive advanced ovarian cancer, the most lethal gynecological malignancy.Niraparib is a potent PARP inhibitor whose safety and efficacy were assessed in the placebo-controlled, randomized clinical trial PRIMA. Niraparib significantly prolonged progression-free survival in the overall population of high-grade advanced ovarian cancer regardless of BRCA and homologous deficiency status compared to placebo. However, the most significant benefit was observed in BRCA mutated and homologous recombination deficient subgroups. Niraparib has a manageable toxicity profile and is well-tolerated by patients. Most common toxicities are hematological and can be managed with drug interruption and dose reduction that do not decrease efficacy. Niraparib is recommended for patients who responded to the first-line chemotherapy with platinum compound regardless of homologous recombination status. This review will discuss the use of niraparib in newly diagnosed advanced ovarian cancer patients focusing on its efficacy and tolerability. Additionally, a case series will be presented to further discuss this drug use in clinical practice in Poland.

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Section: Clinical Efficacy Of Niraparibmentioning

confidence: 53%

Niraparib maintenance in newly diagnosed advanced ovarian cancer — review and case series

Tyszka

Stec

2023

Oncol Clin Pract

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“…The safety profile of niraparib in the PRIMA, PRIME, NOVA, NORA, and QUADRA trials was consistent across multiple lines of treatment (Table 1). [3][4][5][6] Treatment-emergent adverse events of any grade occurred in nearly all patients (≥99%) receiving niraparib, with events grade ≥3 in 51-74% of patients. Serious treatmentemergent adverse events occurred in 18-43% of patients across studies, and fatal treatment-emergent adverse events occured in ≤1% of patients overall (Table 1).…”

Section: Niraparib Clinical Trials and Safety Summarymentioning

confidence: 99%

“…reported in 9-19% of patients. [3][4][5][6] In the NOVA trial, these events tended to occur early and decreased over the first 3 months. The incidence of nausea and vomiting greatly reduced between the first and second month with niraparib (62% vs 13%, respectively, and 20% vs 6%).…”

Section: Reviewmentioning

confidence: 99%

“…1 The introduction of inhibitors of poly (ADP-ribose) polymerase (PARP), a key regulator of DNA damage repair, has significantly enhanced treatment options for advanced epithelial ovarian cancer. 1 2 Niraparib is a PARP inhibitor that improved progression-free survival as a maintenance therapy in multiple clinical trials with manageable toxicity, [3][4][5][6] leading to approval for clinical use. 7 8 Niraparib was first approved by the Food and Drug Administration (FDA) 7 and the European Medicines Agency (EMA) 8 in 2017 as maintenance treatment of recurrent epithelial ovarian cancer after complete response/partial response to platinum-based chemotherapy.…”

Section: Introductionmentioning

confidence: 99%

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Safety and management of niraparib monotherapy in ovarian cancer clinical trials

Monk

González-Martín

Buckley

et al. 2023

Int J Gynecol Cancer

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Niraparib is a poly (ADP-ribose) polymerase inhibitor that has shown a significant improvement in progression-free survival irrespective of biomarker status in patients with advanced epithelial ovarian cancer. This review focuses on the adverse events associated with niraparib and their management to maintain efficacy of niraparib treatment and improve quality of life for patients. In five trials assessing efficacy of niraparib in patients with advanced epithelial ovarian cancer (PRIMA, NOVA, NORA, QUADRA, and PRIME), treatment-emergent adverse events of any grade were reported in nearly all patients (≥99%) receiving niraparib; the events were grade ≥3 in 51–74% of patients. Across all lines of therapy, treatment-emergent adverse events led to dose interruptions in 62–80% of patients receiving niraparib and dose reductions in 47–71%. Hematologic events were most frequently reported, including thrombocytopenia, anemia, and neutropenia. Common non-hematologic events included gastrointestinal events, which were generally low grade (<5% were grade ≥3). Clinical strategies to manage these and other events, such as fatigue and insomnia, cognitive behavioral therapy and pharmacologic agents, are summarized. Once-daily niraparib dosing may be advantageous for some patients for many reasons, including night-time dosing which may help alleviate gastrointestinal symptoms. An individualized starting dose (determined by baseline body weight and platelet count) of niraparib demonstrated an improved safety profile while maintaining efficacy. Patients receiving the niraparib individualized starting dose had fewer grade ≥3 adverse events, dose interruptions, and dose reductions than patients receiving a fixed starting dose. The safety profile of niraparib across five pivotal studies in advanced epithelial ovarian cancer was consistent across multiple lines of treatment, including as maintenance therapy in first-line and recurrent settings and as treatment in heavily pre-treated patients. Long-term safety data from the NOVA trial confirmed that, with appropriate and early dose modifications, niraparib is well tolerated.

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“…Niraparib, one of PARP inhibitors approved as a maintenance therapeutic drug for recurrent ovarian cancer regardless of the presence of BRCA mutations, shows promising e cacy in patients with or without BRCA mutations [1,2]. Although the PRIMA/PRIME and NOVA/NORA clinical studies found signi cant clinical e cacy of niraparib in patients with BRCA1/2 mutant ovarian cancer, the e cacy was reduced in wild-type BRCA patients, especially wild-type BRCA/HRD-negative [1][2][3][4]. Therefore, improving the e cacy of niraparib in patients without BRCA mutations is urgently required.…”

Section: Introductionmentioning

confidence: 99%

Progesterone Acts Synergistically with Niraparib in Ovarian Cancer by Promoting Ferroptosis via the PR/SCD1/ Fatty Acid Oxidation Pathway

Fang

Zhang

et al. 2022

Preprint

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PARP inhibitors (PARPi) play an increasing role in the treatment of ovarian cancer (OC). However, more than 40% BRCA1/2-deficient patients do not respond to PARPi, and wild-type BRCA cases have no significant benefit. Here, we demonstrated progesterone acted synergistically with niraparib in ovarian cancer cells with or without BRCA deficient. This synergism has been confirmed in the ovarian cancer organoid model and in vivo experiments. Furthermore, progesterone can enhance activity of niraparib in ovarian cancer via ferroptosis induction by upregulating progesterone receptor (PR)/SCD1-mediated fatty acid metabolism and enhancing mitochondrial damage. In clinical cases, PR and SCD1 were expressed at higher levels in PARPi sensitive cases compared with resistant cases, and high PR expression was associated with improved prognosis and higher sensitivity to PARPi in OC. This study provides new strategies for improving the efficacy of PARPi in ovarian cancer.

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Efficacy and safety of niraparib as maintenance treatment in patients with newly diagnosed advanced ovarian cancer using an individualized starting dose (PRIME Study): A randomized, double-blind, placebo-controlled, phase 3 trial (LBA 5)

Cited by 41 publications

References 0 publications

Niraparib maintenance in newly diagnosed advanced ovarian cancer — review and case series

Niraparib maintenance in newly diagnosed advanced ovarian cancer — review and case series

Safety and management of niraparib monotherapy in ovarian cancer clinical trials

Progesterone Acts Synergistically with Niraparib in Ovarian Cancer by Promoting Ferroptosis via the PR/SCD1/ Fatty Acid Oxidation Pathway

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