ZEJULA is a poly(ADP-ribose) polymerase (PARP) inhibitor indicated:...for the treatment of adult patients with advanced ovarian, fallopian tube, or primary peritoneal cancer who have been treated with three or more prior chemotherapy regimens and whose cancer is associated with homologous recombination deficiency (HRD) positive status defined by either:...a deleterious or suspected deleterious BRCA mutation, or...genomic instability and who have progressed more than six months after response to the last platinum-based chemotherapy.

Newly Diagnosed Ovarian Cancer….Recommendation 2.1….For those who are HRD positive, determined using FDA-approved companion diagnostic tests, rucaparib and niraparib are options.

In patients with homologous recombination-proficient tumors, the median TFST was 3.7 months longer in patients receiving niraparib than in patients receiving placebo (HR = 0.64, 95% CI 0.46–0.90, P < 0.0105). PFS2 data show point estimates HR < 1, as shown in Table 1 (20% data maturity in overall population)....Preliminary data on TFST and PFS2 were supportive of a clinical benefit of niraparib therapy in a broad population of patients with ovarian cancer following response to first-line chemotherapy.

The median duration of progression-free survival in patients with homologous-recombination deficiency was 21.9 months with niraparib and 10.4 months with placebo (hazard ratio for disease progression or death, 0.43; 95% confidence interval [CI], 0.31 to 0.59; P<0.001)...Within the population with homologous-recombination deficiency, the median duration of progression-free survival was 22.1 months in the niraparib group and 10.9 months in the placebo group (hazard ratio, 0.40; 95% CI, 0.27 to 0.62) in the subgroup with BRCA mutations and 19.6 months and 8.2 months, respectively (hazard ratio, 0.50; 95% CI, 0.31 to 0.83), in the subgroup without BRCA mutations....

Patients in the niraparib group had a significantly longer median duration of progression-free survival than did those in the placebo group, including 21.0 vs. 5.5 months in the gBRCA cohort (hazard ratio, 0.27; 95% confidence interval [CI], 0.17 to 0.41), as compared with 12.9 months vs. 3.8 months in the non-gBRCA cohort for patients who had tumors with homologous recombination deficiency (HRD) (hazard ratio, 0.38; 95% CI, 0.24 to 0.59)...

...Participant who is able to provide tumor slides obtained during cytoreductive surgery for a prospective examination of the homologous recombination deficiency (HRD)....

...- Diagnosis of triple negative breast cancer or ovarian cancer, or any cancer histology with the presence of alteration in BRCA1, BRCA2, PARP metabolism, DNA repair pathways and HRD (homologous recombination deficiency) genes in the metastatic site as described in Section 9.2 using a CLIA-certified assay....

...Patients must be gBRCA mutation or HRD positive...

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...Participants must agree to undergo tumor homologous recombination deficiency/deficient (HRD) testing, and this test result must show that participants have an HRD-positive tumor (defined by the presence of a deleterious or suspected deleterious breast cancer gene (BRCA) mutation or be positive for genomic instability) by the central laboratory selected by the sponsor....

...Monotherapy treatment of adult participants with recurrent ovarian, fallopian tube or primary peritoneal cancer who have been treated with three or more prior chemotherapy regimens with either a) BRCA mutation (irrespective of platinum sensitivity) or b) platinum-sensitive HRD positive....

...Progression-Free Survival (PFS) in Cohort With No Germline BCRA With Homologous Recombination Deficiency-positive (HRD+) Tumors (Non-gBRCAmut HRD+)`PFS was defined as the time between randomization and disease progression or death from any cause. ...

...- Participants must have high-grade serous or endometrioid or high-grade predominantly serous or endometrioid histology, regardless of homologous recombination deficiency (HRD) or germline breast cancer susceptibility gene (gBRCA) mutation status....

...Primary Analysis Population comprised of participants who received 3 or 4 prior lines of therapy (LOT), had homologous recombination deficiency positive (HRDpos) tumors, had platinum-sensitive disease, and were poly(adenosine 5'-diphosphate [ADP]-ribose) polymerase inhibitors (PARPi) naïve.`...

Twenty-two patients all received niraparib at a bolus of 200 mg/d. Fifty percent of patients with high-grade serous ovarian cancer are HRD-positive....two patients achieved partial response (PR) and one patient achieved stable disease (SD), yielding objective response rate (ORR) of 33.3%...