FDA Approves Niraparib for HRD+ Advanced Ovarian Cancer

The FDA has approved niraparib (Zejula) for the treatment of patients with advanced ovarian, fallopian tube, or primary peritoneal cancer who have been treated with ≥3 prior chemotherapy regimens, and whose cancer is associated with homologous recombination deficiency–positive status.

The FDA has approved niraparib (Zejula) for the treatment of patients with advanced ovarian, fallopian tube, or primary peritoneal cancer who have been treated with ≥3 prior chemotherapy regimens, and whose cancer is associated with homologous recombination deficiency (HRD)—positive status.1

The approval is based on results from the single-arm, phase II QUADRA study (NCT02354586), which showed that niraparib elicited an overall response rate (ORR) of 24% (95% CI, 16-34), which was comprised of all partial responses, in the primary efficacy population of patients who had HRD and who received ≥3 prior lines of therapy (n = 98).2 The estimated median duration of response was 8.3 months (95% CI, 6.5—not estimable).

HRD is defined by either a deleterious or suspected deleterious BRCA mutation, or genomic instability in patients with disease progression ≥6 months after response to the last platinum-based chemotherapy. Simultaneously with the niraparib approval, the FDA also approved the Myriad myChoice companion diagnostic assay to determine HRD-positive status in patients with advanced ovarian cancer who are eligible to receive niraparib in the late-line treatment setting.

"Ovarian cancer has a high rate of recurrence, so there is a real need for therapies for women whose cancer has progressed through multiple lines of treatment and who have few or no options left," lead study investigator Kathleen Moore, MD, director, Oklahoma TSET Phase 1 Program, and associate professor in the Section of Gynecologic Oncology, Stephenson Cancer Center, University of Oklahoma, stated in a press release.3 "It’s meaningful to see that Zejula has been approved as a late-line treatment for women including those with and without BRCA mutations.”

In the multicenter, open-label, single-arm, phase II QUADRA study, researchers evaluated the safety and efficacy of niraparib in 463 adult patients with metastatic, relapsed, high-grade serous epithelial ovarian, fallopian tube, or primary peritoneal cancer who previously received ≥3 lines of chemotherapy. Patients could not have prior exposure to PARP inhibitors on the study, and those without BRCA mutations must have progressed ≥6 months after their last dose of platinum-based therapy. HRD-positive status was determined using the Myriad myChoice CDx as either tumor BRCA mutated (n = 63) and/or a genomic instability score ≥42 (n = 35).

Patients received oral niraparib at 300 mg daily continuously, beginning on day 1 in 28-day cycles until disease progression. The primary endpoint was the proportion of patients achieving an investigator-assessed confirmed overall response in patients with HRD-positive tumors—which include both patients with and without BRCA mutations—who were sensitive to their most recent platinum-based therapy who had received 3 or 4 prior anticancer therapies. Also, efficacy analyses were conducted in all dosed patients with measurable disease at baseline.

The median age was 63 years (range, 39-91), the majority of patients were white (82%), and all patients had an ECOG performance status of 0 (59%) or 1 (41%).

At the time of data cut-off on April 11, 2018, 21 patients remained on therapy. Patients had received a median 4 (IQR 3-5) prior lines of therapy; moreover, the median follow-up for overall survival (OS) was 12.2 months (IQR 3.7-22.1). Thirty-three percent of patients were resistant and 35% were refractory to the last administered platinum therapy. The median duration of treatment for the indicated-QUADRA population was 4 months (range, 0.1-30), and was 3 months (range, 0.03-32) in the overall population.

In patients with BRCA-mutant ovarian cancer, the ORR was 39% (95% CI, 17-64) in patients with platinum-sensitive disease, 29% (95% CI,11-52) in those with platinum-resistant disease, and 19% (95% CI, 4-46) in patients with platinum-refractory disease. For those with platinum-sensitive, genomic instability score—positive disease, and did not have BRCA mutations, the investigator-assessed ORR was 20% (95% CI, 8-37).

Regarding safety, the most common adverse events (AEs) that led to dose reductions or interruptions (73%) were anemia (21%), thrombocytopenia (40%), neutropenia (11%), nausea (13%), vomiting (11%), fatigue (9%), and abdominal pain (5%). Serious AEs that occurred in 3% patients included small intestinal obstruction (7%), vomiting (6%), nausea (5%), and abdominal pain (4%). AEs that led to permanent discontinuation occurred in 21% of patients, and fatal AEs occurred in 2% of patients, including cardiac arrest.

"This new indication reinforces our commitment to providing treatment options for more women impacted by ovarian cancer, especially those with high unmet needs," Axel Hoos, MD, PhD, SVP Oncology R&D, GlaxoSmithKline, the developer of niraparib, stated in the press release. "We look forward to continuing our clinical development program of Zejula and understanding its full potential as a treatment for people living with ovarian cancer."

Niraparib was initially approved by the FDA in March 2017 for the maintenance treatment of adult patients with recurrent epithelial ovarian, fallopian tube, or primary peritoneal cancer who are in complete or partial response to platinum-based chemotherapy.


  1. FDA approves niraparib for HRD-positive advanced ovarian cancer. FDA. Published October 23, 2019. https://bit.ly/35YNYya. Accessed October 23, 2019.
  2. Niraparib Prescribing Information. FDA. Published October 23, 2019. https://bit.ly/35Y6xCx. Accessed October 23, 2019.
  3. GSK Announces U.S. Food and Drug Administration Approval of Additional Indication for Zejula (niraparib) for Late-line Treatment for Women with Recurrent Ovarian Cancer. GlaxoSmithKline. Published October 23, 2019. https://bit.ly/33YY5ky. Accessed October 23, 2019.