PARP Inhibitors in Ovarian Cancer Treatment

Video

The utilization and effectiveness of using PARP inhibitors in treating ovarian cancer is considered.

Shannon Westin, MD: For this patient, when it comes to the choice of maintenance, we have touched on that a little. Based on what you decided to treat the patient with up front, intraperitoneal chemotherapy—the choice of niraparib for a patient who has homologous or combination deficient disease—is absolutely appropriate. Because this patient is coming off chemotherapy, you have to be aware of the types of adverse effects and toxicities you can see with niraparib specifically, as well as PARP inhibitors in general if you’re using a different PARP inhibitor in the maintenance setting.

These drugs are tolerable, but they are not without adverse effects. Counseling and setting patient expectations is very important to make sure your patient stays on drug. For all the PARP inhibitors, you are going to watch for cytopenia. You are going to watch for gastrointestinal issues like nausea, vomiting, and feeling full soon. You are going to see these certain class effects like fatigue. Those effects are going to be similar across the different PARP inhibitors.

For certain PARP inhibitors, you might see more of 1 problem vs another. If we are talking about this patient going on niraparib, the cytopenias are there; the most common cytopenia is likely thrombocytopenia, or reduced platelets. However, what we know is that if we utilize a smart dosing strategy to start our patient on the right foot, we can often significantly reduce the severity of that thrombocytopenia.

We use the “weights and plates” dosing. If your patient is less than 77 kg or has less than 150 platelets, you reduce the severity of the thrombocytopenia and hopefully keep your patient on dose consistently. For this agent, we will watch labs very closely during that first month. We check CBC [complete blood count] weekly to watch the platelets specifically, but we also look at hemoglobin and white blood cell count. After you get through that first month, you can extend it out to a monthly basis. This is really what I talk to patients about: During those first couple of months, we are trying to figure out your sweet spot. We have to figure out what dose works well for you or what dose you can tolerate. Once we get through those first couple of months, typically, you really can have your patients on a consistent dose, feeling good and living their life.

Transcript edited for clarity.

Case: A 68-Year-Old Woman With Recurrent Ovarian Cancer

Initial Presentation

  • A 68-year-old female presented with abdominal bloating, discomfort and decreased appetite
  • PMH: unremarkable, postmenopausal; no known family history of cancer
  • PE: abdominal distention, right lower quadrant tenderness on palpation

Clinical work-up

  • Pelvic exam with transvaginal ultrasound showed a right ovarian mass
  • Chest/abdomen/pelvis CT with contrast revealed a right adnexal 4-cm mass, inguinal lymph node involvement and ascites, no pleural effusion
  • Lymph node, adnexal mass biopsy, and paracentesis (1500 cc) cytology confirmed high-grade epithelial ovarian cancer
  • Germline molecular testing: HRD+, BRCA1/2-
  • CA-125, 385 U/mL
  • Diagnosis: Stage 4, high-grade epithelial ovarian cancer
  • ECOG PS 0

Treatment

  • Patient underwent TAH/BSO, lymph node dissection, with optimal debulking; R0
  • IP/IV paclitaxel/carboplatin; PR
  • Followed by niraparib maintenance

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