Niraparib for the treatment of ovarian cancer

Abstract

Niraparib, an orally available selective inhibitor of poly(adenosine diphosphate-ribose) polymerase (PARP), is the first PARP inhibitor approved for use in patients with ovarian cancer who do not harbor a germ-line or somatic mutation in the breast cancer gene (BRCA). Overall, niraparib is well tolerated and its toxicities, primarily hematologic, are manageable especially with recently released initial dose modification guidelines based on weight and baseline platelet count. The role of niraparib as maintenance following frontline platinum-based chemotherapy as well as in the treatment of recurrent high-grade serous ovarian cancer is an active area of investigation. Areas covered: This review focuses on niraparib, its pharmacology, clinical efficacy, and adverse effects as evidenced by prospective clinical trials, and licensed indications. Expert commentary: Niraparib introduced the use of PARP inhibitors regardless of biomarker status. Recent studies highlight the critical need for more accurate biomarkers to identify patients most likely to benefit from treatment with PARP inhibitors. In the next 5 years, we anticipate further expansion of and elucidation regarding the optimal indication for use of niraparib in the treatment of ovarian cancer.

The Role of Secondary Cytoreductive Surgery in Primary Platinum-sensitive Recurrent HGSOC Patients With Different BRCA1/2 Mutation Status: a Retrospective Study

“…In recent years, a large number of studies have con rmed the signi cant survival bene t of BRCAmut patients with PARP inhibitors (28)(29)(30)(31), therefore, the use of PARP inhibitors might conceal he bene t of SCS. In addition, the bene t of PARP inhibitors in BRCAwt patients was relatively limited (28,32), so the bene t of SCS was still remained. The occurrence of this situation was similar to the GOG-0213 (8).…”

“…Secondly, 56.2% of the BRCAmut patients were treated with PARP inhibitors, which could improve the therapeutic effect of BRCAmut patients by synthetic lethality (26,27). In recent years, a large number of studies have con rmed the signi cant survival bene t of BRCAmut patients with PARP inhibitors (28)(29)(30)(31), therefore, the use of PARP inhibitors might conceal he bene t of SCS. In addition, the bene t of PARP inhibitors in BRCAwt patients was relatively limited (28,32), so the bene t of SCS was still remained.…”

Antitumor efficacy of PARP inhibitors in homologous recombination deficient carcinomas

“…The most commonly mutated HR genes include PTEN (5.8%), BRCA2 (2.8%), and ATM (1.2%). Another approach to assess the HRD status of tumor samples is the usage of commercial diagnostic tests . These commercial tests in general can gauge a broad spectrum of molecular markers associated with DNA repair pathways, including LOH, telomeric allelic imbalance, large‐scale state transitions, and microsatellite instability.…”

“…Another approach to assess the HRD status of tumor samples is the usage of commercial diagnostic tests. 24 These commercial tests in general can gauge a broad spectrum of molecular markers associated with DNA repair pathways, including LOH, telomeric allelic imbalance, large-scale state transitions, and microsatellite instability. With the clinical utility of NGS and commercial HRD tests, more novel players will be identified and serve as reliable biomarkers for individualized PARP inhibition therapy.…”

<p>Prognostic Significance and Related Mechanisms of Hexokinase 1 in Ovarian Cancer</p>

“…2 Approximately 60-70% of patients are at an advanced stage when they are diagnosed. 3 The primary treatment for OC is surgery supplemented by chemotherapy. 4 Although new treatment methods have been developed in recent years, the prognosis of patients remains very poor.…”