819P Efficacy and safety of niraparib in older patients (pts) with advanced ovarian cancer (OC): Results from the PRIMA/ENGOT-OV26/GOG-3012 trial

Valabrega, Giorgio; Pothuri, Bhavana; Oaknin, Ana; Graybill, Whitney; Sanchez, A.B.; McCormick, Christine B.; Baurain, J.F.; Hoskins, Paul; Denys, Hannelore; O’Cearbhaill, Roisin E.; Heitanen, S.; Moore, Richard G.; Knudsen, Anja Ør; Rouge, T. De La Motte; Heitz, Florian; Levy, Tally; Li, Y.; Gupta, Dhiraj; Monk, Bradley J.; Martín, Antonio González

doi:10.1016/j.annonc.2020.08.958

Cited by 9 publications

(9 citation statements)

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“…Another unexpected adverse event is insomnia, very common (incidence ≥ 1/10) in niraparib-treated patients (grade 1–4: 24.3% of niraparib group in NOVA trial; 26.4% in PRIMA trial) [ 65 , 66 , 73 ].…”

Section: Efficacy and Safety Of Niraparibmentioning

confidence: 99%

Differences in PARP Inhibitors for the Treatment of Ovarian Cancer: Mechanisms of Action, Pharmacology, Safety, and Efficacy

Valabrega

Scotto

Tuninetti

et al. 2021

IJMS

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Poly(ADP-ribose) polymerases (PARP) are proteins responsible for DNA damage detection and signal transduction. PARP inhibitors (PARPi) are able to interact with the binding site for PARP cofactor (NAD+) and trapping PARP on the DNA. In this way, they inhibit single-strand DNA damage repair. These drugs have been approved in recent years for the treatment of ovarian cancer. Although they share some similarities, from the point of view of the chemical structure and pharmacodynamic, pharmacokinetic properties, these drugs also have some substantial differences. These differences may underlie the different safety profiles and activity of PARPi.

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Section: Efficacy and Safety Of Niraparibmentioning

confidence: 99%

Differences in PARP Inhibitors for the Treatment of Ovarian Cancer: Mechanisms of Action, Pharmacology, Safety, and Efficacy

Valabrega

Scotto

Tuninetti

et al. 2021

IJMS

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“…For safety, three studies reported partial data in the elderly population regarding only hematologic toxicity. 21 25 27 The main characteristics of the included studies are listed in Table 1 . The risk of bias in the selected studies was globally low ( Online Supplemental Figure 2 ).…”

Section: Resultsmentioning

confidence: 99%

“…17 In the metastatic setting, maintenance of PARP inhibitors improved disease-free survival in both newly diagnosed and pretreated patients. [18][19][20][21][22][23][24][25][26][27][28] The majority of the studies considered the two age subgroups of <65 and ≥65 years. However, as women aged 65 and more are under-represented in the clinical trials, there is limited prospective evidence of efficacy and safety in this age group.…”

Section: Original Researchmentioning

confidence: 99%

Efficacy and safety of PARP inhibitors in elderly patients with advanced ovarian cancer: a systematic review and meta-analysis

Maiorano

Lorusso

et al. 2022

Int J Gynecol Cancer

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BackgroundPoly-(ADP-ribose)-polymerase (PARP) inhibitors have shown to be effective as maintenance treatment in patients with advanced ovarian cancer. Although most ovarian cancers develop after age 65, older patients are often under-represented in clinical trials.ObjectiveTo assess the efficacy and safety of PARP inhibitors versus placebo as maintenance therapy in older patients with ovarian cancer.MethodsThis systematic review and meta-analysis was performed in accordance with the Preferred Reporting Items of Systematic reviews and Meta-Analysis (PRISMA) guidelines. We searched PubMed, Embase, Cochrane databases, and the American Society of Clinical Oncology (ASCO), European Society of Medical Oncology (ESMO), Society of Gynecologic Oncology (SGO) meeting abstracts, for randomized clinical trials using maintenance with PARP inhibitors in patients with advanced ovarian cancer, up to June 30, 2021. The measured outcomes were progression-free survival and safety (number and grade of adverse events), stratified by age (cut-off point: 65 years).ResultsA total of eight phase III trials were selected. Among the 4364 patients, 1435 (32.9%) were aged ≥65 (919 receiving PARP inhibitors, 516 receiving placebo). Compared with placebo, maintenance with PARP inhibitors improved progression-free survival in older patients (HR=0.54; 95% CI 0.45 to 0.65; p<0.00001). No differences were found in progression-free survival in comparison with a younger population (HR=0.47; p=0.13). Only hematologic adverse events were available for the age subgroups, and no differences emerged for all-grade hematologic adverse events (risk ratio (RR)=1.22, p=0.33 for anemia; RR=0.97, p=0.74 for neutropenia) and severe neutropenia (RR=0.97, p=0.86); old women were at lower risk of severe anemia (RR=0.79, p=0.04) but had a higher risk of severe thrombocytopenia (RR=1.27, p=0.01).ConclusionsMaintenance with PARP inhibitors prolongs progression-free survival compared with placebo, both as monotherapy and combined with chemotherapy or bevacizumab, in older patients with advanced ovarian cancer (high-quality evidence). Hematologic safety is similar to that seen in younger patients. No overall survival data are available at this time.PROSPERO registration numberCRD42021261039.

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“…Patient-reported outcomes from the PRIMA trial have shown that patients with epithelial ovarian cancer receiving niraparib did not experience deterioration in their health-related QoL compared with placebo. Scores were comparable for niraparib and placebo regardless of age group (<65 or ≥65 years, or <75 or ≥75 years) 35 or BRCA mutation status in PRIMA. 28 29 Likewise, patients with recurrent disease treated with niraparib in NOVA had similar patient-reported outcomes as those receving placebo; there were no significant differences between treatment arms.…”

Section: Niraparib Trial Datamentioning

confidence: 91%

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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819P Efficacy and safety of niraparib in older patients (pts) with advanced ovarian cancer (OC): Results from the PRIMA/ENGOT-OV26/GOG-3012 trial

Cited by 9 publications

References 0 publications

Differences in PARP Inhibitors for the Treatment of Ovarian Cancer: Mechanisms of Action, Pharmacology, Safety, and Efficacy

Differences in PARP Inhibitors for the Treatment of Ovarian Cancer: Mechanisms of Action, Pharmacology, Safety, and Efficacy

Efficacy and safety of PARP inhibitors in elderly patients with advanced ovarian cancer: a systematic review and meta-analysis

Safety and management of niraparib monotherapy in ovarian cancer clinical trials

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