Updated FDA Approvals for PARP Inhibitors in Ovarian Cancer


An expert gynecologic oncologist comments on recent revisions to FDA-approved indications for PARP inhibitors in the treatment of ovarian cancer.

Case: A 55-Year-Old Woman with BRCA-Mutated Ovarian Cancer

  • A 55-year-old presents to her PCP for heartburn and abdominal pain that started approximately 2 years earlier.
  • Imaging: Transvaginal US showed bilateral ovarian masses; CT reveals masses in adnexa, largest measuring 5.8 cm, with evidence of liver capsule and retroperitoneal lymph node involvement.
  • Labs: CA125, 3600 U/mL
  • Surgical intervention: She underwent hysterectomy, omentectomy, appendectomy, and debulking; residual disease was left on liver and diaphragm, approximately 2.2 cm
  • Diagnosis: stage IIIc, high-grade serous ovarian cancer
  • IHC testing: p53 (+)/ PAX 8 (+) /WTI and CK 7 (+)
  • Germline testing: BRCA1 mutation
  • Treatment: She received IV carboplatin/paclitaxel
  • TRAEs: She experienced myelosuppression, most notably neutropenia (post cycle 3) that required postponement of next cycle
  • Follow-up imaging: showed complete clinical remission after completion of chemotherapy; CA125, 30.5 U/mL
  • Maintenance therapy with a PARPi was initiated.
  • At week 3, her hemoglobin is 7.0 g/dL and she receives a transfusion


Leslie Randall, MD, MAS: For physicians who use PARP inhibitors in the recurrent setting, there are some important updates that have come out in the last year. Our first approval for olaparib was for[patients with] germline BRCA [mutations] in the fourth line or greater as treatment. The extended datasets for that group show the overall survival with a potential decrement in overall survival. Those of us who do clinical trials don’t believe that that is a statistically valid assessment, because it’s not powered to show the overall survival advantage. There’s crossover among the arms for the patients who were on olaparib vs chemotherapy and the control arms.

Nonetheless, there does appear to be a numerical-potential detriment in overall survival. Out of an abundance of caution, this was pulled from the market. Most patients are getting it in earlier lines of therapy, and we’re not repeating PARP [inhibitors] after we’ve given once. It wasn’t as critical. It wasn’t as big of a loss as it would have been had we not hadPARP [inhibitors] move up to the front line. Similarly, the [results from the] ARIEL4 trial [NCT02855944], which was rucaparib vs physician’s choice chemotherapy, showed a PFS [progression-free survival] advantage from rucaparib, but again showed a potential overall survival decrement. Same issues with that study. [It was] not powered to show that crossover dropout, so not the best statistical assessment. Out of an abundance of caution and because it was available for earlier lines, that indication was also pulled from the market.

One that is more concerning to me personally is the [restriction] of…niraparib for platinum-sensitive recurrent disease for patients who don’t have BRCA-mutated disease [based on data from the NOVA trial (NCT01847274). If the patient did not get PARP [inhibitors] in the front line—patients often don’t get PARP [inhibitors] in the front line—and they have a platinum-sensitive recurrence, that has historically been [an] important option for our patients in that setting. However, for overall survival concerns for platinum-sensitive [recurrence], niraparib maintenance has been retracted, but only in the patients who don’t have [BRCA-mutated disease]. You can still use it for [patients with BRCA-mutated disease]. Olaparib is still available for platinum-sensitive recurrent, biomarker-unrestricted patient population in that setting.

Transcript edited for clarity.

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