Niraparib as First-Line Maintenance Treatment of Ovarian, Fallopian Tube, Primary Peritoneal Cancer

Pharmacy Times Oncology Edition, April 2022, Volume 4, Issue 2

The oral PARP inhibitor is associated with increased PFS, regardless of BRCA mutational status.

Niraparib (Zejula; Glaxosmithkline) is an oral PARP inhibitor approved in adult patients with ovarian cancer or with fallopian tube or primary peritoneal cancers.1

Although the mainstay of treatment for newly diagnosed advanced epithelial ovarian cancer involves surgery and platinum-taxane chemotherapy, up to 85% of patients with advanced ovarian cancer will have disease recurrence after treatment.2 In these patients, niraparib is associated with increased progression-free survival (PFS), regardless of the presence or absence of BRCA gene mutations.2

Indications and Dosage

Niraparib is indicated as a first-line maintenance therapy for patients with either advanced or recurrent ovarian, fallopian tube, or primary peritoneal cancer who are in complete or partial response to platinum-based chemotherapy.1

Additionally, niraparib is indicated as a primary treatment for patients with advanced ovarian, fallopian tube, or primary peritoneal cancer in patients who meet the following criteria1:

  • They have been treated with 3 or more prior chemotherapy regimens.
  • They have cancer associated with homologous recombination deficiency (HRD)-positive status defined by either a deleterious or suspected deleterious BRCA gene mutation or genomic instability accompanied by disease progression more than 6 months after response to the last platinum-based chemotherapy.

Lastly, to determine eligibility for treatment with niraparib, providers must use an FDA-approved companion diagnostic tool for the selection process.1,3

The table details niraparib dosing based on indication.1

Patients may take niraparib with or without food. Upon the occurrence of adverse reactions, patients should consider interruption of treatment, dose reduction, or dose discontinuation. The package insert includes additional information on these dosage modifications for reference.1

Lastly, the treatment dose of niraparib for patients with hepatic impairment is 200 mg by mouth once daily.1

Mechanism of Action

Niraparib exerts genotoxic activity by targeting rapidly dividing cells.4 It inhibits the enzymes PARP1 and PARP2, interfering with DNA repair by causing single- and subsequently double-stranded DNA breaks; this leads to programmed cell death.1,5

FDA Approval

The FDA approved niraparib in March 2017 following the phase 3 NOVA trial (NCT01847274), which compared niraparib with placebo in 2 independent cohorts consisting of 553 patients who were enrolled based on their BRCA mutation status.4,6 During the study, the investigators evaluated PFS as the primary end point.4

The findings showed that niraparib was associated with a significantly longer median duration of PFS versus placebo, regardless of the patient’s BRCA mutation or HRD status (21 vs 5.5 months, respectively, in the BRCA cohort; 12.9 vs 3.8 months in the non-BRCA, HRD-deficient cohort; and 9.3 vs 3.9 months in the overall non-BRCA cohort).4,6

Adverse Effects

The BOX provides an overview of niraparib’s most common adverse reactions at an incidence of 10% or more.1

Pregnancy and Lactation

For patients who are or may become pregnant in the future, it is important to know that niraparib can result in fetal harm during pregnancy by causing teratogenicity and/or embryo-fetal death because of its disruption of cell division.1 Similarly, health care providers should advise lactating women not to breastfeed during treatment with niraparib and for 1 month after receiving the final dose.1

Lisa E. Ruohoniemi, PharmD, is a clinical staff pharmacist at LewisGale Hospital Montgomery in Blacksburg, Virginia.

REFERENCES

1. Zejula. Prescribing information. GlaxoSmithKline; 2021. Accessed November 2, 2021. https://gskpro.com/content/dam/global/hcpportal/en_US/Prescribing_Information/Zejula_Capsules/pdf/ZEJULA-CAPSULES-PI-PIL.PDF

2. Gonz lez-Mart n A, Pothuri B, Vergote I, et al; PRIMA/ENGOT-OV26/GOG-3012 Investigators. Niraparib in patients with newly diagnosed advanced ovarian cancer. N Engl J Med. 2019;381(25):2391-2402. doi:10.1056/NEJMoa1910962

3. Moore KN, Secord AA, Geller MA, et al. Niraparib monotherapy for late-line treatment of ovarian cancer (QUADRA): a multicentre, open-label, single-arm, phase 2 trial. Lancet Oncol. 2019;20(5):636-648. Published correction appears in Lancet Oncol. 2019;20(5):e242. Lancet Oncol. 2019;20(5):636-648.

4. Ison G, Howie LJ, Amiri-Kordestani L, et al. FDA approval summary: niraparib for the maintenance treatment of patients with recurrent ovarian cancer in response to platinum-based chemotherapy. Clin Cancer Res. 2018;24(17):4066-4071. doi:10.1158/1078-0432.CCR-18-0042

5. About Zejula. Zejula HCP. Accessed November 2021. https://www.zejulahcp.com/what-is-zejula/

6. Mirza MR, Monk BJ, Herrstedt J, et al. Niraparib maintenance therapy in platinumsensitive, recurrent ovarian cancer. N Engl J Med. 2016;375(22):2154-2164. doi:10.1056/NEJMoa1611310