TRK Inhibitors: Precision Medicine in Oncology - Episode 12
Benjamin P. Levy, MD: Mark, what’s your take on genomic profiling, or molecular characterization of tumors within the sarcoma world?
Mark Agulnik, MD: I think most of my peers would do quite similarly. At diagnosis of new metastatic disease, assuming that they had a disease-free interval from original diagnosis to the development of metastatic disease, we usually send off the biopsied specimen. And then, also, as you previously mentioned, some drugs can alter the ability for someone to go to surgery or have a limb-sparing surgery. If someone has stage III disease that potentially is incurable with surgery, we’ll also send off at that point, just to see if we’ll catch anything that potentially is driving it.
Benjamin P. Levy, MD: And it’s all next-generation sequencing [NGS]?
Mark Agulnik, MD: Correct, all next-generation sequencing.
Benjamin P. Levy, MD: Marcia, in the thyroid world?
Marcia S. Brose, MD, PhD: We do thyroid and head and neck. One of the tumors we haven’t talked about is salivary gland tumor, which of course, is where we see most of the TRK fusions. So I’ve got 2 of the highest proportion ones. In thyroid, mostly of course if it’s metastatic, it’s very similar to what you said. I want to reiterate that obviously for metastatic disease, if we don’t know their profile we get it. If we can, we try to get it on a new biopsy. It’s not uncommon for a thyroid cancer patient to have unbiopsiable disease, in which case we would run it on the original. Now, they don’t usually have a lot of chemotherapy and other agents that might change it, so we can sometimes get away. It’s probably not as bad as other cancers that get treated.
But the interesting thing in thyroid is that there are 2 places where molecular testing is happening. There’s a big development of panels that are being used at first diagnosis because 90% of these patients will actually be cured. So those people are getting it because of prognosis and we are trying to push people toward surgery, or even more importantly, against surgery if they possibly don’t need it, because thyroid nodules and even very indolent cancers are so prevalent. I’m pushing for everybody who has RAI [radioactive iodine]-refractory disease to absolutely get tested.
We also have a very high actionable percentage. BRAF, by itself, will give you 50% of papillary thyroid cancer. By the time you do that, and then we have RET translocations, sometimes RET point mutations, and a few other actionable items, we’re starting to push 60%, 70% in the metastatic world. So there is a very high prevalence. And then, salivary gland really has to do with people who haven’t been cured. They’re all getting tested again with NGS.
Benjamin P. Levy, MD: Ed, do you want to round us out in the lung world?
Edward S. Kim, MD: I think it’s kind of a debate in the lung world right now, of doing everyone on a large platform. There are those delays that occur—2 to 3 weeks. I think people get impatient, especially when you have a very nice I/O [immune oncology] triplet that you can give to anyone without testing, which is both good and bad. What we do at our center is a reflex testing on an [Ion] AmpliSeq profile. We get that back in 3 to 4 days. And so we have everything we need quickly. Eventually, everyone does get a large genomic test. We have a trial like TAPUR right now that is a great study that encourages doctors to test and sort of find a match there. We like to build it around that type of platform. But I do see the day, the writing is coming. Up front, everyone is going to be getting large-scale testing. We’ve done that with blood, just as you have, on 1 patient. I remember distinctly that we weren’t as lucky to find something.
John L. Marshall, MD: I thought I was so clever. I’m just late coming to the game.
Edward S. Kim, MD: I felt very sad when Philip was talking about the fine needle versus the core. In BATTLE, our whole thing was getting 2 cores, if not more. I don’t know where the resistance is coming from. I know it’s difficult tumor access. But somewhere in the interventional world, there is this resistance; even in the pathology world. “Oh, don’t call it an FNA [fine-needle aspiration]. It’s based on tumor cell content.” “Well, I’m just basing it on the needle size. I’m sorry. Size matters, OK? I’m sorry.”
Let’s just be frank as to what gauge we’re using here and how many times you’re making a pass and actually looking to see what comes out. The fact that we are still finding alternative, smaller platforms with easier access, which is the same as an FNA, of what you’re doing on the blood testing, which has a utility…. But we still get more information out of the tissue testing, and I think we have to be very mindful and really stubborn about wanting to get that.
Benjamin P. Levy, MD: Yes, I think in the procedure list, interventional radiologists, surgeons all ask: How much tissue do you need? I say, “A boat load of tissue.” I think tissue still remains the gold standard. I’m encouraged by some of the plasma testing results that we’re seeing.
Edward S. Kim, MD: Totally.
Benjamin P. Levy, MD: As well as some of the data that will be presented soon in Atlanta at AACR [the American Association for Cancer Research annual meeting]. Certainly, we’ve made a lot of inroads.
Transcript Edited for Clarity