Safety and management of niraparib monotherapy in ovarian cancer clinical trials

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.

Automated summary

Niraparib, a PARP inhibitor, has shown significant improvement in progression-free survival for advanced epithelial ovarian cancer patients regardless of biomarker status. This review focuses on managing the adverse events associated with niraparib to maintain its efficacy and improve patients’ quality of life. Hematologic events, such as thrombocytopenia, anemia, and neutropenia, were the most commonly reported adverse events, while gastrointestinal events were generally low grade. Clinical strategies including cognitive behavioral therapy and pharmacologic agents are summarized for managing these events. Personalized starting dose of niraparib based on body weight and platelet count demonstrated improved safety profile. Long term safety data from NOVA trial confirmed that niraparib is well tolerated with appropriate and early dose modifications.