Guideline Recommendations for Molecular Testing in Ovarian Cancer

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

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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

Transcript:

Leslie Randall, MD, MAS: The guidelines for molecular testing in ovarian are that all patients should have at least germline BRCA testing. We really extend this now to not just BRCA genes, but also other genes that are BRCA-like, such as BRIP1, RAD51C, RAD51D. Most of us get germline panel testing for all patients. You can do that as the oncologist or in conjunction with genetic counseling. Every society that advises on ovarian cancer, ASCO [American Society of Clinical Oncology], the SGO [Society of Gynecologic Oncology], the IGCS [International Gynecologic Cancer Society], everyone recommends at least this germline BRCA testing for the benefit of the patient in the context of PARP inhibitor therapy post chemotherapy. Also for the patient’s family members: They could get tested, and if positive could be candidates for risk reducing procedures. If the patient carries a BRCA mutation, she’s also at risk for breast cancer and needs to be monitored for that as well. That’s the minimum testing.

Most of us also get HRD [homologous recombination deficiency] testing in addition to that, especially in our BRCA wild-type patients. HRD testing…is available through several vendors either as an HRD score or as a loss of heterozygosity, LOH, score. If those are positive, that portends a great benefit from the PARP inhibition therapy. There are some PARP indications that don’t require any testing, but we feel that this testing is important prognostically and for the overall health of the patient and the family. We recommend that all patients get at least the BRCA testing followed by the HRD testing, if negative. We used to do this in sequence. We used to say, “OK, send the BRCA first and if the germline’s negative, then we’ll reflex and do HRD[testing] on the tumor.” However, it’s logistically very difficult to keep up with who’s had what testing. Now we just send germline—either blood or saliva—and tumor testing for somatic BRCA and HRDat the time of diagnosis. It varies who we send to, and each of the platforms have their pluses and minuses.

As we get more and more clinical trials, we try to get as much information upfront about the tumor. Now many of us are sending NGS [next-generation sequencing] right at the time of diagnosis to get the full panel, the full mutational view of that tumor. We just want to know as much as possible about the tumor. It’s possible from the get-go, even if we’re not using that information right away to treat the patient.

Transcript edited for clarity.