Genetic Testing Becoming More Widespread in Ovarian Cancer, But Challenges Remain

Mike Janicek, MD

Testing for genetic alterations has become an important step in the treatment of patients with ovarian cancer. Although much has been achieved, says Mike Janicek, MD, there needs to be more widespread use of genetic testing in order to push the field forward.

Current guidelines state that any patient diagnosed with ovarian, fallopian tube, or peritoneal cancer should be offered genetic testing. Still, fewer than 20% of patients with breast and ovarian cancer who are eligible for genetic testing undergo it, Janicek says.

OncLive: Have there been any advances in the last year in genetic testing for ovarian cancer?

In an interview during the 2018 OncLive^® State of the Science Summit™ on Ovarian Cancer, Janicek, medical director of the Genetics Division at Arizona Oncology, discussed the importance of genetic testing and how the field can benefit from a better understanding of it through genetic counselors and self-education.Janicek: Yes and no. There has not been enough progress, in my opinion, but I am impatient. It has been 2 decades now since the discovery of the BRCA gene, but we still have not made enough progress in terms of getting the word out and getting testing done. There are estimates that fewer than 20% of patients who have breast or ovarian cancer and are eligible for testing have actually been tested. In the oncology world, the numbers are getting better, but we are still not where we should be. We have a long way to go, despite all of the progress that we have made. I still remain passionate about this.

How do you decide who to test and when?

There have been incremental changes in ovarian cancer with gene panels, targeted therapies, PARP inhibitors, targeting genetic mutations, and immunotherapies. We have made some astounding progress, and we are starting to see genetics creep into other fields such as breast cancer and prostate cancer indications. We are headed in the right direction.Everybody. The guidelines state that everyone with ovarian, fallopian tube, or peritoneal cancer should be offered genetic testing. We no longer think that family history should be the only indicator, because about half of patients who have a mutation with ovarian cancer don’t have a significant family history.

The “when” part of the question is a little more difficult. For a patient with ovarian cancer who just had a major surgery, or debulking, and is recovering and facing the prospect of chemotherapy, throwing genetic counseling and testing into that mix is a little bit difficult upfront, so we typically wait until the second round of chemotherapy when the dust has settled and they are a little bit more accustomed to what has happened to them. They also have a better focus; genetic counseling is complex. It is not just a simple test and then see what we get—it takes preparation and there is a lot that goes into it.

What are the differences and how do you decide which you are going to use?

I am a big fan of genetic counselors; they do a way better job than we do because they have expertise and more time to dedicate [to this area]. I am a big proponent of [patients seeing genetic counselors], but I am not opposed to physicians doing their own genetic testing if they know the basics and are unafraid to tap into a genetic counselor’s expertise [if necessary], and not just wing it. A lot of time goes into [testing]. It is a complicated topic, but there is no going back on this. We need to do more genetic testing; there is more genetic information coming up. It is hard to keep up, but it is a “train that keeps on chugging.” You also spoke on the different methods of testing.Historically, we have focused on germline testing; that is where it was the clearest indication for estimating risk and informing families of their risks. As we have learned more about what causes ovarian and other cancers, the germline has crept into the somatic.

Both are important in different ways; I don’t believe that one replaces the other. It’s a dangerous assumption to think that somatic testing will pick up the germline and vice versa; not all germline mutations show what is going on in the tumor. In my ideal world, we would do both—preferably at the same time. In my ideal world, it would be 1 test that covers both [areas] upfront.

What is the importance of homologous recombination deficiency (HRD)?

Then it gets into the insurance questions. What is covered? The somatic side is very important, but it is not as well covered as the germline side. A lot still needs to be worked out in the clinical oncology and genetics world. It’s definitely a moving target and something that we are still working out.I am a big believer in having as much knowledge as possible to help empower your patient to understand what their response to PARP inhibitors will be. The data are crystal clear that patients with deleterious HRD alterations are predisposed to have a better response to PARP inhibitors.

Does microsatellite instability also play a role in this landscape?

Are there any further challenges or unmet needs with genetic testing in ovarian cancer?

However, when the FDA was looking at the data, they felt that patients who did not have these alterations responded well enough—so the indication disregarded the genetic status. As a clinician, I believe looking a patient in the eye and helping them understand what their likelihood is of responding to a drug is critical. I believe HRD has a role to the clinician and to the patient; however, to the FDA, it’s a different story. They are not mutually exclusive; you can go along with FDA indications, but that should not stop you from knowing as much as you can about a patient’s tumor and their likelihood of response. HRD is important, but there is a bit of a discrepancy between what the FDA thinks is important and what I think is important.Great question. We have finally moved on to universal screening for endometrial and colon cancer, for the most part. Only about 3% of ovarian cancers have a mismatch repair defect. Given the power of some of these immune checkpoint inhibitors for select patients, ruling that out would be a shame. The question is, when to test in that setting? Certainly, endometrial cancer is an easy one. HRD and immune checkpoints are the 2 leading genetically targeted fields that we are actively pursuing, and we are making great progress in those areas.The cost is coming down and the knowledge is growing; we just need to figure out how to educate. The ability to test and get information is outstripping our ability to tell patients what that means. On the flip side, the word is not getting out fast enough to where it is saving lives in real time. There is not a week or 2 that goes by where someone walks in with advanced ovarian cancer that should have been caught earlier.