Maintenance Therapy Treatment Landscape for BRCA-Mutated Advanced Ovarian Cancer
Leslie Randall, MD, MAS, reviews the available treatment options for BRCA-mutated advanced 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
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
Leslie Randall, MD, MAS: The landscape for maintenance is really evolving. Maintenance is so important because you invest so much in the surgery. The patient invests so much in the chemotherapy. It’s a strain on a patient to go through that much therapy. When you complete that therapy, you want an insurance policy on that, to ensure that it’s going to be a lasting effect, especially when they’ve gotten into that complete remission like our patient, and like most of our patients do.
The way maintenance is structured is, if you go by the NCCN [National Comprehensive Cancer Network] guidelines, the first decision to make during chemotherapy is whether a patient is a candidate for bevacizumab. Really all patients [whose disease is] stage IIIC or IV who have had surgery and completed chemotherapy and have not had progression of disease are candidates for bevacizumab maintenance. Some of our patients are not great candidates. Say they have uncontrolled hypertension…or maybe they have inflammatory bowel disease. Those might not be the best candidates for Avastin [bevacizumab], but those are relative contraindications. There are no absolute contraindications. There are some [clinicians] who will select bevacizumab based on the patient’s risk. These high risk features such a pleural effusion, ascites, residual disease, neoadjuvant chemotherapy—none of those is really predictive.
The label for bevacizumab is that any patient [with stage III or IV disease] who’s had surgery and chemotherapy can start on bevacizumab during chemotherapy and continue that throughout the maintenance cycle. The NCCN [guidelines are] really structured around that decision. When patients are on bevacizumab, they would continue that and if they’re not on bevacizumab, then you could consider a PARP inhibitor.
The next decision node is the PARP inhibitor. For patients with germline BRCA mutation, PARP inhibitor is a no-brainer. These patients have tremendous benefit hazard ratio of 0.3 consistently across multiple trials for reduction in progression or death, with PARP inhibition. These patients need PARP inhibitor, period. Whether you continue the bevacizumab based on NCCN guidelines, if you started it, you continue it, you add the PARP inhibitor to the bevacizumab. There are some of us, myself included, who are biased that the PARPinhibitor is so effective for BRCA mutated patients that you might not need to continue the bevacizumab [because] it adds toxicity…. It’s crucial that they get the PARP inhibitor.
For the BRCA wild-type HRD [homologous recombination deficiency] population, this is a group where they also have substantial benefit with a PARP inhibitor. If you started bevacizumab, you continue and add the PARPinhibitor. If you had not started bevacizumab, you just switch them over to a PARP inhibitor at the completion of chemotherapy. For the biomarker negative subgroup, this is a little bit trickier. Patients who have started on bevacizumab can continue on bevacizumab. There’s debate as to whether a patient would benefit from the addition of the PARP inhibitor in this group. If you look at the label of olaparib, which was the only one studied prospectively to date in combination with bevacizumab, it is not approved for this HR [homologous recombination] proficient [HRP] or HRD test–negative population. You would just continue the bevacizumabin that situation. However, the PRIMA label allows for patients who have HRP or HRD test–negative disease. You could switch them over to PARP alone in that situation.
Transcript edited for clarity.