Case 1: Diagnostic Tissue Testing in Ovarian Cancer

Shannon Westin, MD: With that, I will transition over to my colleague. We’re going to move to some case-based discussion so we can hear how about how we utilize these data to make decisions.

Thomas C. Krivak, MD: Shannon, that was an absolutely wonderful summary of past data and current data. Thank you for that great presentation. It’s always a pleasure to work with you and to be talking about patient care with respect to ovarian cancer.

We’re going to talk about a case: a newly diagnosed ovarian cancer patient, BRCA wild type, HR [homologous recombination]–deficient. This patient is a 49-year-young woman. She is African American and has a chronic hepatitis B infection and mild hypertension. Her mother died of breast cancer, and her mother’s side of the family had ovarian cancer at age 65. CT [computerized tomography] scan shows ascites and a bilateral adnexal mass at 8 cm. She has an elevated CA-125 [cancer antigen 125] at 285 U/mL. She was seen by tumor oncology and underwent exploratory laparotomy, followed by omentectomy, bilateral salpingo-oophorectomy, pelvic lymph node dissection, appendectomy, and resection of pelvic nodules, and she was optimally debulked to no gross residual disease to microscopic disease.

With how Dr Westin has highlighted some of the testing and some of the stratification, what testing would we order at this point? When do we typically test for BRCA 1/2 mutations? Do we test for somatic mutations in the tumor? How do you test? Are you routinely testing for HRD [homologous recombination deficiency]? I can start by answering these, and what I would say is that, at this point, I don’t want to say that there’s confusion, but there are a lot of options. For somebody with advanced-stage, high-grade, serous ovarian cancer, we know that the NCCN [National Comprehensive Cancer Network] Guidelines, ASCO [American Society of Clinical Oncology], and SGO [Society of Gynecologic Oncology] say that these patients should be referred on for germline testing. In our office we’re referring these patients to our geneticist, and they’re getting germline panel testing.

What we’re also trying to do is, if patients are BRCA1 or BRCA2 negative or panel-test negative, we’re starting to send most of the tumors for HRD testing with the Myriad myChoice test, in that we’ll look for somatic mutations as well as do the genomic instability score. We don’t do things together; we do them sequentially. We’ll test the patient, then test the tumor, and then use those results, because in my opinion, for this patient who’s being treated, she needs surgery plus platinum-based chemotherapy—bevacizumab if you’d like—and then we’ll have to decipher how we’re going to do her maintenance therapy.

In the absence of BRCA1 and BRCA2 mutations, HRD status may give us more information about the benefit of PARP inhibitor therapy. I’m a firm believer of this. Information is very important, which is why I like the HRD test, and when you talk about an HRD status, you should describe in your progress note how you are defining that HRD status. Is it a BRCA germline mutation? Is it a somatic mutation? Is it a genomic instability score from Myriad myChoice? Is it a FoundationFocus LOH [loss of heterozygosity] score? I’m sure there are other companies such as Tempus [Labs] that may come out with an HRD score at some point. Caris Life Sciences, Inc, does say it has some HRD testing, and Ambry Genetics Corp does do some next-generation sequencing. There are many tests out there. It’s important that, when you say somebody is HRD or has homologous recombination deficiency, you define that. That’s important because all the tests are not created equal.

These are the 2 tissue tests that are available. For Myriad myChoice, you can see there the companion diagnostic for niraparib first approved with QUADRA and now approved with PAOLA, and again Foundation Medicine. You can dig a little deep into how these tests were developed. Myriad myChoice has the 3 components you can see listed below: loss of heterozygosity, telomeric allelic imbalance, and large-scale state transitions. They have these 3 scores that they put together to try to help capture BRCA-like tumors. You heard a lot of discussions at SGO [Annual Meeting] about the different score ranges and things, but to me the Myriad myChoice was designed to grasp or to capture BRCA-like patients.

The Foundation Medicine score is an LOH score, and when you look at how that test was developed, they looked at that test, and it was developed alongside using rucaparib in ARIEL3. It was a test that, when they looked at the percentage, they tried to guide the percentage cutoff by how patients responded on treatment. The tests were developed a bit differently and measure HRD slightly different. How you test folks is important and how you describe it is important.

Transcript edited for clarity.