Treatment Considerations for PARP Inhibitors in Ovarian Cancer

EP: 1.Patient Profile: A 55-Year-Old with BRCA-Mutated Ovarian Cancer

EP: 2.Guideline Recommendations for Molecular Testing in Ovarian Cancer

EP: 3.Maintenance Therapy Treatment Landscape for BRCA-Mutated Advanced Ovarian Cancer

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EP: 4.Treatment Considerations for PARP Inhibitors in Ovarian Cancer

EP: 5.Managing Adverse Events from PARP Inhibitors in Ovarian Cancer

EP: 6.Recent Long-Term Data on PARP Inhibitors in Ovarian Cancer

EP: 7.Updated FDA Approvals for PARP Inhibitors in Ovarian Cancer

EP: 8.Future Outlook of the Ovarian Cancer Treatment Landscape

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

Transcript:

Leslie Randall, MD, MAS: To select a PARP inhibitor, we have 2 that are on label and available. One is olaparib, and that is approved for either germline BRCA mutated or for HRD [homologous recombination deficient]-positive patients and BRCA mutated in combination with bevacizumab. It’s the biomarker that helps you select initially. Niraparib is on label for all comers, but not in combination with bevacizumab as a single agent. Whether you’ve started bevacizumab or not, and what your biomarker profile looks like, that is how we select which PARP inhibitor to go with.

Treatment-related neutropenia, most of our patients are on growth factor support or dose reductions. Neutropenia during chemotherapy is not too big of a problem from the baseline. Even for patients who have neutropenia, that is not predictive of difficulty administering a PARP inhibitor. PARP inhibitors are associated with neutropenia, but it’s manageable and monitorable, and the chemotherapy situation does not predict what happens from a neutropenia standpoint.

In general, you want all of their toxicity to resolve to at least a grade 1. You want that to be more manageable. Particular [adverse]effects, especially if you’re starting niraparib, such as the thrombocytopenia, really need to be resolved to at least 100,000 platelet count, but most of us feel more comfortable more at 150 [150,000 platelet count]. We typically wait about 6weeks to start the PARP inhibitor after the completion of chemotherapy.That allows these toxicities to resolve and for patients to get back to normal. Some patients will still have lingering grade 2 neurotoxicity from the taxane. There’s not overlapping PARP inhibitor toxicity with the neurotoxicity. I don’t withhold PARP inhibitor until that resolves to grade 1. It might not. You can go ahead in that situation, but all other toxicities resolved to grade 1.

When I counsel my patients, I’m very pro maintenance. I want them to be on some maintenance, and I want them to be on the maintenance that is the most effective for their biomarker type. I try to balance toxicity with efficacy. That’s why I often don’t use combination therapy for my BRCA-mutated patients. I want them on a PARP inhibitor. For the BRCA wild type HRD test–positive patients, they likely benefit more from the combination of a PARP inhibitor with bevacizumab. As long as the toxicities are manageable, which they typically are; then that would be usually my go-to. For the HRP [homologous recombination proficient] population, I’m pretty biased to give PARP inhibitor in that setting. The reason being is that the availability of PARP in later lines of therapy is going away. The HR [homologous recombination]-proficient patients have a higher rate of platinum-resistant disease. They’re not going to be candidates for PARP inhibitor later.

Patients should [receive a] PARP inhibitor and bevacizumab both at some point in their journey. The bevacizumab can be given in multiple lines of therapy. It can be given in the frontline, the platinum sensitive recurrent [setting], the platinum resistant recurrent setting. You have more opportunity to give bevacizumab. This may be the patient’s only opportunity to get PARP. I typically would use PARP inhibitor, but I don’t use dual therapy in that HR-proficient population. Although there are incoming data that may start to challenge that stance.

Transcript edited for clarity.