Table 1.

FDA risk–benefit assessment

DimensionEvidence and uncertaintiesConclusions and reasons
Analysis of condition
  • Ovarian cancer is the fifth cause of cancer death in women and represents 5% of all cancer deaths.

  • In 2018, it is estimated that there will be 22,240 new cases of ovarian cancer and that 14,070 women will die in the United States.

  • Recurrent epithelial ovarian, fallopian tube, or primary peritoneal cancers are serious, life-threatening, and incurable.

Current treatment options
  • Most patients with ovarian cancer receive primary debulking surgery followed by chemotherapy with platinum plus taxanes with or without bevacizumab. Response rates in the first-line setting are high, but most patients will develop a recurrence within 2 years and die within 3 to 4 years of diagnosis.

  • Prior to the current approval, bevacizumab was the only FDA-approved maintenance therapy for the treatment of recurrent epithelial ovarian, fallopian tube, or primary peritoneal cancer.

Benefit
  • Niraparib demonstrated statistically significant and clinically meaningful improvement in PFS over placebo in both the gBRCAm cohort (HR, 0.26; 95% CI, 0.17–0.41; P < 0.0001) and the non-gBRCAm cohort (HR, 0.45; 95% CI, 0.34–0.61; P < 0.0001).

  • Evidence of effectiveness was supported by a statistically significant and clinically meaningful PFS improvement.

Risk
  • The most common adverse reactions (AR) experienced (≥20%) were thrombocytopenia, anemia, neutropenia, leukopenia, palpitations, nausea, constipation, vomiting, abdominal pain/distention, mucositis/stomatitis, diarrhea, fatigue/asthenia, decreased appetite, headache, insomnia, nasopharyngitis, dyspnea, rash, and hypertension. AML/MDS, bone marrow suppression, and cardiovascular effects are the AR described in the warnings and precautions section of labeling.

  • The observed PFS benefits outweigh the risks in this patient population, which represents an unmet medical need.

Risk management
  • Niraparib is intended to be prescribed by oncologists who are well versed in the identification and management of the toxicities associated with niraparib.

  • Labeling details dose interruption, reduction, or discontinuation.

  • AML/MDS, bone marrow suppression, and cardiovascular effects are the AR being described in the warnings and precautions section of labeling.

  • Laboratory and vital sign monitoring are recommended before and during treatment.

  • The safe use of niraparib can be managed through accurate labeling and routine oncology care.