COPENHAGEN – Women with platinum-sensitive, recurrent ovarian cancer treated with the PARP 1/2 inhibitor niraparib had significantly longer progression-free survival than did women who received a placebo, regardless of their BRCA mutational status, according to results of a phase III trial.
Median progression-free survival (PFS) among women with germline BRCA mutations who received niraparib was 21 months, compared with 5.5 months for women with germline BRCA mutations who received placebo (P less than .001).
For the overall population of women with no germline mutations, median PFS was 9.3 months for those who received niraparib, vs. 3.9 months for placebo-treated controls. Among women in this group whose tumors tested positive for homologous recombination deficiency (HRD), median PFS was 12.9 months, vs. 3.8 months without HRD.
Jon Smith/Frontline Medical News
Dr. Mansoor Raza Mirza
Dr. Mirza reported results of the The NGOT-OV16/NOVA trial, the first phase III trial with a PARP inhibitor, at the European Society for Medical Oncology Congress. Results of the trial were simultaneously published online in The New England Journal of Medicine.
Niraparib is a selective, oral inhibitor of poly(adenosine diphosphate-ribose) polymerase (PARP) 1 and 2 that was previously shown to have efficacy against ovarian cancer in a phase I dose-escalation trial.
In the NGOT-OV16 NOVA trial, patients with platinum-sensitive high grade serous ovarian cancer first underwent chemotherapy with 4-6 cycles of a platinum-based regimen, and those who responded to platinum treatment were then stratified by the presence or absence of germline BRCA mutations, and then randomized on a 2:1 basis to either niraparib 300 mg once daily or placebo until disease progression.
A total of 203 patients with germline BRCA mutations and 350 with no mutations were enrolled in the trial.
As noted before, patients treated with niraparib in both trials arms had significantly longer PFS than did controls. The hazard ratio (HR) for niraparib in patients with germline BRCA mutations was 0.27. For the overall non–germline mutation population, the HR was 0.45, and for HRD-positive and HRD-negative subgroups, the HRs were 0.38 and 0.56, respectively (the latter is an exploratory endpoint, however; P less than .001 for the first three HRs shown).
Secondary efficacy endpoints, including chemotherapy-free interval and time to first subsequent treatment, also favored niraparib in patients with and without BRCA mutations.
Overall survival data for the trial are not sufficiently mature for reporting, however.
The safety profile of the drug was in line with that seen in other studies of PARP inhibitors, Dr. Mirza said. Grade 3/4 adverse events occurring in 5% or more of patients included thrombocytopenias in 33.8% of niraparib recipients vs. 0.6% of controls, anemia in 25.3% vs. 0%, neutropenia in 19.6% vs. 1.7%, fatigue in 8.2% vs. 0.6%, and hypertension in 8.2% vs. 2.2%.
Five of the 367 patients who received niraparib (1.4%) developed myelodysplasia or acute myeloid leukemia, compared with 2 of 179 patients (1.1%) treated with placebo.
Patient-reported outcomes measured via the Functional Assessment of Cancer Therapy – Ovarian Symptom Index and EQ (EuroQol) 5D-5L instrument showed high compliance rates and patient-reported symptom rates that were similar between niraparib and placebo groups.
Dr. Sandro Pignata
The results also demonstrated that HRD testing can be used to identify patients without germline mutations in BRCA who may benefit from a PARP inhibitor, he said.
Tesaro funded the study. Dr. Mirza disclosed serving on the board of directors of the pharmaceutical companies, and consultant or advisory roles with multiple other companies. Dr. Pignata disclosed consulting, honoraria, and or research funding from several companies, but reported no relationship with Tesaro