Maintenance treatment with the novel agent niraparib improved progression-free survival (PFS) compared with placebo for patients with recurrent ovarian cancer harboring a germline BRCA (gBRCA) mutation or homologous recombination deficiency (HRD).
Maintenance treatment with the novel agent niraparib improved progression-free survival (PFS) compared with placebo for patients with recurrent ovarian cancer harboring a germline BRCA (gBRCA) mutation or homologous recombination deficiency (HRD). These top-line findings from the phase 3 NOVA trial were announced today by the developer of the PARP inhibitor, Tesaro.
In the study, niraparib improved median PFS by 15.5 months versus placebo for patients responding to platinum-based chemotherapy who harbored a gBRCA mutation. In those with non-gBRCA-mutated tumors with HRD-positivity, there was a 9.1-month PFS advantage seen with niraparib versus placebo. Based on these results, Tesaro plans to submit regulatory filings to the FDA and EMA.
"The majority of women who are diagnosed with advanced ovarian cancer will experience a relapse of their disease, even if they respond to their initial chemotherapy," Thomas Herzog, clinical director, University of Cincinnati Cancer Institute, said in a statement. "New treatment options are needed to extend the time in between cycles of platinum-based chemotherapy for these patients, and the results from the NOVA study suggest that niraparib could represent an important new treatment option for many patients with ovarian cancer."
The phase 3 study enrolled more than 500 patients across two independent cohorts that randomized patients two-to-one to receive niraparib at 300 mg daily or placebo. The first cohort enrolled patients with gBRCA mutations and the second enrolled individuals who were not gBRCA-positive but were either HRD-positive or HRD-negative. The HRD-positive group could include those with somatic BRCA alterations. HRD testing was conducted using Myriad’s myChoice HRD test.
Patients in the trial had histologically confirmed ovarian, fallopian tube, or primary peritoneal cancer that was high-grade serous histology or had a known gBRCA mutation. All patients had received at least two prior courses of platinum-based therapy and were considered platinum sensitive. The primary endpoint of the study was PFS, with secondary outcome measures focused on overall survival and safety.
The median PFS in gBRCA mutation carriers was 21.0 months with niraparib versus 5.5 months with placebo, representing a 73 percent improvement in the risk of progression or death. For those with HRD-positive tumors, the median PFS was 12.9 months with niraparib versus 3.8 months with placebo.
Niraparib continued to show a benefit over placebo for patients with ovarian cancer regardless of HRD or gBRCA status. In the cohort of patients with non-gBRCA mutations who were either HRD-positive or HRD-negative, the median PFS was 9.3 months with niraparib versus 3.9 months with placebo, representing a 55 percent improvement with the PARP inhibitor.
The most frequently observed grade 3 or 4 treatment-emergent adverse events (AEs) with niraparib were thrombocytopenia (28.3 percent), anemia (24.8 percent) and neutropenia (11.2 percent). Overall, 14.7 percent of patients discontinued treatment with niraparib during the trial compared with 2.2 percent of those in the control arm. The rates of secondary MDS or AML were similar between the niraparib and placebo arms (1.3 percent versus 1.2 percent, respectively).
"Importantly, these results show activity of niraparib in a population of ovarian cancer patients beyond those with germline BRCA mutations. In keeping with our mission of responsible drug development, NOVA was designed to define those patients most likely to benefit from niraparib treatment and, in so doing, optimize the benefit/risk profile for patients," Mary Lynne Hedley, president and COO of Tesaro, said in a statement. "We believe we have achieved that goal and look forward to presentation of the full data set from this study at the European Society for Medical Oncology congress in October."
Niraparib continues to be developed in various settings for patients with cancer. The single-arm phase 2 QUADRA trial is exploring niraparib in patients with high-grade serous ovarian cancer who were previously treated with at least three prior lines of chemotherapy. The phase 3 PRIMA study is looking at the PARP inhibitor as a frontline therapy for women with ovarian cancer. In breast cancer, the phase 3 BRAVO study is comparing the medication with physician's choice for those with gBRCA-mutant breast cancer.