Niraparib in Late-Line Treatment of Ovarian Cancer


Key Points

  • The response rate was 28% in patients with HRD-positive tumors sensitive to their last platinum-based therapy.
  • Response was observed in 10% of all evaluable patients.

In the phase II QUADRA trial reported in The Lancet Oncology, Moore et al found that the poly(ADP-ribose) polymerase (PARP) inhibitor niraparib was active in fourth- or later-line treatment of ovarian cancer, particularly in patients with homologous recombination deficiency (HRD)-positive, platinum-sensitive disease.

Study Details

The study included 456 patients (modified per-protocol population; total population = 463) with relapsed, high-grade serous (grade 2 or 3) epithelial ovarian, fallopian tube, or primary peritoneal cancer who had been treated with at least 3 previous chemotherapy regimens. Treated patients were from 50 sites in the United States and Canada, and enrolled between April 2015 and November 2017.

Patients received oral niraparib at 300 mg once daily continuously in 28-day cycles until disease progression. The primary endpoint was investigator-assessed confirmed overall response among patients with HRD-positive tumors (including those both with and without BRCA mutations) sensitive to their last platinum-based therapy who had received three or four previous regimens and were PARP inhibitor–naive (primary efficacy population). Among all patients, 26% of patients were sensitive, 33% were resistant, and 35% were refractory to their last administered platinum therapy, with 7% having unknown platinum status.


Among 47 patients in the primary efficacy population, a response was achieved in 13 (28%; P = .00053 vs null hypothesis of ≤ 10%). The median duration of response was 9.2 months. A total of 32 patients (68%) achieved disease control. Median progression-free survival in this population was 5.5 months.

In total, a response was observed in 38 patients, constituting 10% of 387 response-evaluable patients (those with at least 1 evaluable postbaseline tumor scan) and 8% of 456 in the modified per-protocol population. The median duration of response was 9.4 months. Median overall survival in the modified per-protocol population was 17.2 months. Median overall survival was 26.0 months in the BRCA-mutated population, 19.0 months in the HRD-positive population (including both BRCA-mutated and non–BRCA-mutated disease), and 15.5 months in the HRD-negative population.

Adverse Events

The most common treatment-related grade ≥ 3 adverse events were anemia (24%) and thrombocytopenia (21%). Serious adverse events occurred in 43% of patients, with the most common being small intestinal obstruction (7%), thrombocytopenia (7%), and vomiting (6%). Adverse events led to treatment discontinuation in 21% of patients. One death—due to gastric hemorrhage—was considered related to treatment.

The investigators concluded, “We observed clinically relevant activity of niraparib among women with heavily pretreated ovarian cancer, especially in patients with HRD-positive, platinum-sensitive disease, which includes not only patients with a BRCA mutation but also a population with BRCA wild-type disease. We identified no new safety signals. Our data support expansion of the treatment indication for [PARP] inhibitors to include patients with HRD-positive ovarian cancer beyond those with BRCA mutations.”

Kathleen N. Moore, MD, of the Stephenson Cancer Center, University of Oklahoma, Oklahoma City, is the corresponding author for The Lancet Oncology article.

Disclosure: The study was funded by Tesaro. The study authors’ full disclosures can be found at

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