Case 1: Stage IV, High-Grade, Serous Epithelial Ovarian Cancer
Dr Thomas C. Krivak reviews a case of a 59-year-old woman who has stage IV, high-grade serous epithelial ovarian cancer and discusses ASCO and NCCN guideline recommendations for germline/somatic tumor testing.
Thomas C. Krivak, MD: Thank you for joining us for this Targeted OncologyTM Virtual Tumor Board®, which is focused on the practice updates in ovarian cancer. In today’s presentation, my colleagues and I will review 3 clinical cases. We will discuss individualized approaches to the use of PARP inhibition in first-line maintenance therapy setting and we’ll share our perspectives on key clinical trial data that may impact our decisions. I am Tom Krivak from the Allegheny Health Network in Pittsburgh, Pennsylvania. And today I’m joined by Dr Cecelia Boardman from HCA Virginia Health System in Richmond, Virginia, as well as Dr John Chan from Sutter Health in San Francisco, California, and Ashley Farione, PA-C, from the Allegheny Health Network in Pittsburgh, Pennsylvania. Thank you for joining us. Let us get started with our first case.
Our first case is going to be a patient with stage IV, high-grade, serous epithelial ovarian cancer [HGSOC]. This patient is a 59-year-young patient who is 150 pounds, who presents with abdominal bloating, discomfort, and modest weight loss. Her past medical history is significant for having hypercholesterolemia that’s well controlled on medications, she’s postmenopausal, with no known family history of cancer. On her physical exam, she does have some diffuse tenderness on abdominal palpation, as well as some abdominal bloating. She has a good functional status with an ECOG [Eastern Cooperative Oncology Group] performance status of 1.
Her initial clinical work-up included a pelvic exam as well as transvaginal ultrasound, and this revealed about 5 cm bilateral adnexal masses. The CT scan of the chest, abdomen, and pelvis with contrast again reveals bilateral adnexal masses, approximately 5 cm, as well as pelvic and inguinal lymphadenopathy. There was no pleural effusion. She then underwent a paracentesis which revealed 2300 cc’s of fluid and confirmed a high-grade serous ovarian cancer, and her CA 125 [cancer antigen 125] is 460. This is somebody that we’ll commonly see in our clinic settings.
For discussion, we’d like to talk about what do the ASCO [American Society of Clinical Oncology] as well as the NCCN [National Comprehensive Cancer Network] guidelines recommend regarding germline and somatic testing in advanced-stage ovarian cancer, as well as when do you typically test for BRCA mutation status and/or homologous recombination deficiency, and within that, how important is germline as well as somatic testing in ovarian cancer. Should all patients undergo both germline and somatic testing? When should patients be tested, as well as how does this molecular testing aid in your treatment approach?
The ASCO guidelines summarizing germline and somatic tumor testing in patients with advanced-stage ovarian cancer you can see are summarized here. Basically, any woman diagnosed with epithelial ovarian cancer should be offered germline genetic testing for BRCA1 and BRCA2, and other ovarian cancer susceptibility genes at the time of diagnosis. With respect to that, those patients who do not carry a germline mutation in BRCA1 or BRCA2, should consider and should be reflexed to somatic tumor testing to look for BRCA1 and BRCA2 mutations as well. Those patients with identified germline or somatic or likely pathologic BRCA1/BRCA2 variants, these patients should be offered some treatment in accordance with the FDA [Food and Drug Administration] approved indications for upfront treatment of ovarian cancer with maintenance therapy. Then you can see down here it talks about first- or second-degree blood relatives of the patient with ovarian cancer and a known germline pathologic variant within BRCA, or any of those other genes, should be offered individualized genetic risk assessment and undergo genetic counseling and testing for that. Obviously for that, we’re looking for an ounce of prevention is better than a pound of cure, to do risk-reducing surgery, and help prevent ovarian cancer. You can see there that with most of these genetic testing’s, a lot of people will do this in their office, but if you have a genetic counselor available or somebody who is familiar with genetics, they should be involved in the development of a strategy to help best test these patients.
The bottom line there is it’s important to always remind patients that variants of uncertain significance, we should be careful about making clinical decisions based on what we call a VUS [variant of uncertain (or unknown) significance]. Again, that’s a mouthful with respect to the ASCO guidelines for germline and somatic testing, but it’s a very nice summary that looks at how we should be looking at panel testing, germline testing, reflexing to some tumor testing, to capture some of the great data that we have with respect to upfront treatment of patients with advanced-stage ovarian cancer and maintenance treatments.
The NCCN guidelines are similar. What you can see here is that they want to go ahead and do tumor molecular analysis as indicated with utilizing next-generation sequencing [NGS] for BRCA1 or BRCA2 as well as other somatic mutations, and you can see they add on additional testing such as IHC [immunohistochemistry] for MMR [mismatch repair] proteins, looking for Lynch syndrome and other potential medications that are going to target those abnormalities. Again, in addition to BRCA1 or BRCA2 testing, there are other HR genes [homologous recombination] that may be involved, again looking at panel tests as well as testing NGS within the tumor and additional somatic testing at the physician discretion. You can see on the right-hand side here, it talks about when you have an absence of BRCA1 or BRCA2 genetic abnormalities, you can evaluate these patients for homologous recombination deficiency [HRD] to help define and help make clinical decisions with respect to utilization of maintenance therapy either in the upfront setting as well as recurrent setting.
With respect to the HRD tests that are available at this time, there are many tests out there, the 2 that we’ll highlight right now is the Myriad myChoice as well as the FoundationOne. With both the Myriad as well as the FoundationOne, you’re going to have next-generation sequencing for BRCA1 and BRCA2. With respect to the Myriad myChoice, what you’re going to have is an HRD test that’s going to look at and evaluate 3 components: loss of heterozygosity, telomeric allelic imbalance, as well as large-scale state transitions. It’s going to use a composite score to say if somebody is homologous recombination deficient with their tumor, or homologous recombination proficient. You can see the FDA approvals with niraparib [Zejula] October 23, 2019, most likely with the QUADRA data, as well as with olaparib [Lynparza] and bevacizumab [Avastin] with the PAOLA data, using this in upfront therapy. And then with respect to Foundation, they’re going to have next-generation sequencing across the tumor, as well as develop an LOH [loss of heterozygosity] score to help define what is HR deficient for respect to those types of tumor tests, and again companion medication is rucaparib [Rubraca].
Transcript Edited for Clarity
Avutometinib/Defactinib Leads to Positive Response, Survival Data in Ovarian Cancer
October 18th 2024The completion of a new drug application for the combination of avutometinib and defactinib in KRAS-mutant ovarian cancer is expected to be finalized with the FDA by the end of the month.
Read More
