Ling Jun Chen, Mercer University College of Pharmacy
According to the American Cancer Society, epithelial ovarian cancer has the highest mortality of any gynecological tumor.  Platinum- and taxane-based chemotherapy regimens have been suggested as first-line treatments for ovarian cancer. It has been shown that the effectiveness of these treatments diminish over time due to accumulating dose-related toxicity. 
Niraparib is a poly ADP-ribose polymerase (PARP) inhibitor, which inhibits both DNA repair and programmed cell death. It is an oral, once-daily medication that is currently being evaluated in four ongoing trials. Niraparib is an investigational agent and the U.S. Food and Drug Administration has not approved it. 
|Niraparib Maintenance Therapy in Platinum Sensitive, Recurrent Ovarian Cancer |
|Design||Randomized, placebo-controlled, phase 3 trial; N= 553|
|Objective||To evaluate the efficacy and safety of niraparib versus placebo as maintenance treatment|
|Study Groups||Germline BRCA (n= 203): Niraparib (n=138), placebo (n= 65); non-gBRCA cohort (n= 350): Niraparib (n= 234); placebo (n= 116)|
|Methods||Patients were categorized according to the presence or absence of a germline BRCA (gBRCA) mutation. A BRCA mutation is a mutation in either of BRCA1 and BRCA2 genes, which are tumor suppressor genes. All patients were platinum-sensitive and had recurrent ovarian cancer. They were randomly assigned in a 2:1 ratio to receive niraparib 300 mg or placebo once daily.|
|Duration||August 2013 to June 2016|
|Primary Outcome Measure||Duration of progression-free survival|
|Baseline Characteristics||Germline BRCA mutation||No germline BRCA Mutation|
|Median age, years (range)||57 (36-83)||58 (38-73)||63 (33-84)||61 (34-82)|
|Cancer stage, n (%)|
|I or II||23 (16.7)||10 (15.4)||22 (9.4)||5 (4.3)|
|III||95 (68.8)||46 (70.8)||173 (73.9)||86 (74.1)|
|IV||20 (14.5)||9 (13.8)||38 (16.2)||24 (20.7)|
|Time to progression after penultimate platinum therapy, n (%)|
|6 to <12 months||54 (39.1)||26 (40.0)||90 (38.5)||44 (37.9)|
|≥12 months||84 (60.9)||39 (60.0)||144 (61.5)||72 (62.1)|
|Complete response to recent platinum therapy||71 (51.4)||33 (50.8)||117 (50.0)||60 (51.7)|
|Previous lines of chemotherapy, n (%)|
|2||70 (50.7)||30 (46.2)||155 (66.2)||77 (66.4)|
|≥3||67 (48.6)||35 (53.8)||79 (33.8)||38 (32.8)|
|Results||Duration of progression-free survival|
|Niraparib, month||Placebo, month||Hazard Ratio||95% CI||p-value|
|gBRAC mutation||21.0||5.5||0.27||0.17 – 0.41||<0.001|
|Non-gBRAC mutation with homologous recombination deficiency positivity||12.9||3.8||0.38||0.24 -0.59||<0.001|
|3.9||0.45||0.34 – 0.61||<0.001|
|Adverse Events||Common Adverse Events: nausea (73.6%), fatigue (59.4%), anemia (50.1%), constipation (39.8%), vomiting (34.3%), headache (25.9%), hypertension (19.3%)|
|Serious Adverse Events: thrombocytopenia (61.3%), neutropenia (30.2%), myalgia (8.2%)|
|Percentage that Discontinued due to Adverse Events: 9.3% (due to hematologic abnormalities)|
|Study Author Conclusions||The duration of progression-free survival in patients with platinum-sensitive, recurrent ovarian cancer was significantly longer in the niraparib group than in the placebo group, regardless of the presence or absence of gBRCA mutations or homologous recombination deficiency status. The treatment-associated myelotoxicity required dose modifications or delays but was not associated with a long-term increase in mortality or morbidity.
Niraparib maintenance therapy is a breakthrough for patients with recurrent ovarian cancer because it provides significant clinical benefit regardless of BRCA status. It cumulates less toxicity and adverse effects compared to platinum-based chemotherapy. Study does not address niraparib dose individualization and more research is needed on this front to avoid treatment-associated myelotoxicity. A limitation specific to the medication could be the adverse event profile, which showcased a particularly high rate of hematologic abnormalities.
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- Mirza MR, Monk BJ, Herrstedt J, et al. Niraparib Maintenance Therapy in Platinum-Sensitive, Recurrent Ovarian Cancer. N Engl J Med. 2016.