Genomic Testing is Good But Not Great, According to Expert

Pharmacy Times welcomes back Dr. Ramaswamy Govindan, MD, a medical oncologist at the Washington University School of Medicine in Saint Louis, Missouri, who continues his discussion about genomic sequencing tests to identify cancer gene mutations. Govindan discusses how these tests can help place patients in appropriate clinical trials, the test’s current pitfalls, and benefits that may extend beyond its original function.

PT Staff: How does genomic sequencing inform clinical trial eligibility?

Ramaswamy Govindan, MD: That's also an excellent question, to be honest with you. And, you know, unfortunately, when you have somebody with EGFR-mutant lung cancer, for example, I wish I could tell you take this pill for 10 days and all your lung cancer can be cured. I wish we could say that, but we are not there at this point. And even if these patients take these pills for a year or 2, eventually these tumor cells escape the effects of these drugs and become resistant to this. And now we are coming up with better drugs, or drugs that may work in the setting where the initial drug for a particular gene alteration stopped working.

And so we have a number of clinical trials, as you mentioned, and for us to place patients on a specific trial is not only important—what are gene alteration that tumor cells had to begin with— but what subsequent alterations have taken place. For example, the same EGFR-mutant patients, they give EGFR inhibitor therapy. Let's say a year or 2 goes by and the tumor cells become resistant. We now biopsy those tumors doing the sequencing again because the mechanism of resistance varies depending on various situations. So a given tumor with the EGFR-mutant lung cancer may have amplification of a gene called methyltransferase 1 (MET1) for instance, or may have picked up a secondary mutation— the same EGFR gene that may have accounted for resistance— when there's drug therapy stopped working. It's important to study not only what happened to begin with, but also when the drugs stopped working, and then you can place them on appropriate clinical trials.

So we do the sequencing in some instances multiple times over the course of the life of a patient. And you're so right that we do need sequencing the cells to place them on the property at trials. And that is so critical.

PT Staff: Could there be other (better?) ways to use genomic tests?

Ramaswamy Govindan, MD: Once again, a great question. You know, initially, we began testing the tumor for a specific gene alteration. For example, if you're looking for kirsten rat sarcoma viral oncogene homolog (KRAS) p.G12C mutation, there were polymerase chain reaction (PCR) tests looking only for that. Then we began to do the next generation sequencing, where we can look at the panel of genes; it can be all 20,000 genes or can be few 100 genes or a few 1,000 genes. And you don't have to look for a specific genotype, you look for anything that's not considered normal, or common. And now, the technology has developed to such an extent that now we can do this in peripheral blood. And now we do this routinely in the clinic, where patients give us a tube of blood, we send this for testing, and we look for tumor DNA in the peripheral blood. And we often get the results within 5 to 7 days, in some instances, even sooner than that.

And here is the good and the bad part. The good part is so easy for patients, especially if you have a tiny biopsy, there's not enough tumor cells to do the gene sequencing and the tumor cells, or peripheral blood gives you a great opportunity to find these alterations in these patients. And they are if they're present, for example, the known mutations in this common gene that cause cancer are easy to recognize and when appropriate, we use that for therapies.

But the flip side, the not so good part, is that the number (one-third of the time at least in lung cancer), for a specific gene alteration in the tumor may not show up in the blood test. In other words, the blood test can be falsely negative. So you have to keep in mind that if it is present, known gene alteration in a given tumor. Now that we've studied parts of this lung cancer tumors, we can decide therapy based on the peripheral blood DNA sequencing. But in some instances, you may have completely normal tumor cells, or the blood test will not pick up the tumor cells may have the gene alterations, so we got to go back and biopsy if we don't have initial biopsies. So you got to keep that in mind, especially in patients who don't have that much metastatic disease diseases confined to the chest, you may not find that in the peripheral blood. So that's something to keep in mind. It's a good test, but not a great test. And so, you got you got to keep that.

PT Staff: Final thoughts?

Ramaswamy Govindan, MD: The point I would make is that now we have tools and technologies to really identify the alterations in the tumor genes, we can do it in the peripheral blood, we can use tumor cells, and we are getting better and better and figuring this out. Eventually, we may use these kinds of technologies to identify patients who are cured or not cured after initial surgery or radiation therapies or definitive therapies as we call an early-stage cancers. A lot of research is currently going on and seeing whether we can do these kinds of a peripheral blood testing to figure out who may have occult cancer, who may have cancer that they don't know about— in other words, cancer screening. And so this technology is evolving very rapidly and I think I think it's important to pay attention to the space be really be well become knowledgeable about the evolving nature of the science, technology, research etc. I'm quite optimistic about this.