Peter Anderson, MD, Pediatric Hematologist-Oncologist at the Cleveland Clinic talks about how the drug RETEVMO is helping patients with Medullary Thyroid Cancer.
What are the signs and symptoms of thyroid cancer? What should people be looking for?
Dr. Anderson: It is a relatively common type of cancer that has minimal symptoms. It could be from an overactive thyroid, under active thyroid or a lump. Usually it comes to people’s attention because something is different, and they see their family doctor. It could be physical discomfort, or they just do not feel well.
How common is thyroid cancer? Have we seen the rates go up or is it stabilizing?
Dr. Anderson: It is slowly increasing, and I think it is because we can detect it better. An Ultrasound is an extremely sensitive way to look for nodules in the thyroid. Many nodules are found and not all are cancerous, but they can detect them. Then with extremely sensitive means they can see if it is thyroid cancer.
Talk about Medullary Cancer. What is it and what does it impact?
Dr. Anderson: Medullary thyroid carcinoma has a genetic predisposition where one copy of the RET gene has a mutation that causes the cancer. Some patients are born with the RET mutation but sometimes it is a random event where the medullary thyroid cells have a new mutation of the RET gene ret drives the cancer. Although it is unusual and a subset of thyroid cancer, if RET is mutated we have a clue as to what causes these cells grow into a cancer. This RET mutation is a target of a new drug.
How prevalent is medullary thyroid cancer in the United States and is it hard to detect?
Dr. Anderson: It is extremely rare. You are probably talking between one in fifty thousand to one in a hundred thousand people. For those who have MTC, it is important to be treated with very good multidisciplinary care for not only the surgery to remove the bulk of the cancer but for the endocrinologist to make sure the impaired thyroid function is followed and taken care of. Then if you have metastases there are specific treatments the oncologist can use.
It is a genetic mutation so is there a double-edged sword? It is rare but you know what is driving it so you can look for treatments.
Dr. Anderson: Yes and no. If you are born with the mutation, you should get screened and make sure you are in a medical system that can detect it. There are other kinds of cancers that if you have the RET mutation in your germline DNA. For example you might get another cancer called pheochromocytoma. If it is what we call somatic mutation ( in the tumor DNA only) this gives you a clue as to what treatments to use. This new drug is called LOXO-292 or selpercatinib. Before that we had very non-specific treatments that would for example inhibit growth factors for new blood vessels. They were approved for other uses and had a lot of toxicity. So, it was difficult for patients- and doctors. But once this extremely specific RET inhibitor drug came out, we not only saw responses but with MUCH less toxicity too.
Can you tell me a little bit more about this drug, selpercatinib (LOXO-292)?
Dr. Anderson: It is a drug developed by a small company. I remember going through the first, second, third and fourth-line drugs that were not working very well. When I asked , Vivek Subbiah used LOXO-292 *selpercatinib) M.D. Anderson about getting LOXO-292 for a teenager, Dr. Subbiah said he had just treated a patient who was in hospice and miserable with pain from all the metastasis and after LOXO-292was incredibly effective. Dr. Subbiah was so impressed he recommended the company treat teenagers and we quickly put the amendment through our IRB to get permission for a pediatric patient. It was heart-warming to see the response of the Cleveland Clinic Clinical Research Unit to help get our 17 year old patient on the study and get all the required labs, too. For me it was one of the better experiences I have ever had in oncology: seeing a patient with widely metastatic cancer have his health restored with an oral investigational drug. In this case it was the patient’s liver was full of cancer; it was also widely spread to bones and lungs. Within 1 month the patient went back to high school, gained weight, and became healthy again. So, when you see things like that from just taking pills twice a day it makes you proud to be part of an organized team at Cleveland Clinic that made it possible.
Was the patient out of options?
Dr. Anderson: Yes. It was going to be hospice or try to give him palliative radiation for pain. We had already gone through the standard treatments.
What kind of promise does this drug have and is it just for thyroid cancer or does it hold promise for other genetic cancers?
Dr. Anderson: If the tumor has the right mutation in the RET gene it should work. Some lung cancers and pheochromocytomas have this mutation. I think what we’re seeing is the FDA will eventually approve many drugs based on molecular target and not the type of cancer; this would be a good example of the initial FDA approval.
Could you give me an explanation of how this works in the system, and how the drug works on the cancer to bring it under control?
Dr. Anderson: When you have a mutated gene, it is like an on switch for some cancers. The cancer requires that for growth and for the cells to divide. It tricks the body into getting more nutrients whether it is glucose or things that are needed to grow. If you can flip that switch off then the cancer which is addicted to this mutation all of a sudden can’t grow and it realizes it’s a metabolic mass and it undergoes a process we call apoptosis where the cells die. So, it is a pretty impressive way to target cancer. But it requires an extremely specific mutation to target and protein the drug that interacts with it.
Just to clarify the patient was in the clinical trial.
Dr. Anderson: Yes. He signed the consent form several times first when he turned 18, then as the study had improvements. Yes He was part of the pivotal trial that resulted in FDA approval.
Who are the best candidates for this therapy? Someone who nothing else really worked or does there have to be some genetic testing to ensure they might be a good target?
Dr. Anderson: We have a next generation sequencing (NGS) panel that identifies the RET mutation. If you get a diagnosis of medullary thyroid cancer even though the pathologists say this is under the microscope you need to take the next step and do the molecular test.
When you see the patient for follow ups what goes through your head?
Dr. Anderson: I saw him today. We went through the activities of his daily life. Like any young man, he plays video games, and is attending Kent State. I think he is maturie and has a great life perspective, and is motivated. I can be there for his medical therapy and looking at a scan, but he’ll make a difference for many in the long run because he’s had a close call and it makes you appreciate things so much more.
Is there anything I did not ask you that you want to make sure people know either about the patient or about the drug and treatment for this kind of thyroid cancer?
Dr. Anderson: The world has become a small place and patients talk to each other. It is amazing how much they learn from other patients with rare cancers. I have seen this in the medullary thyroid carcinoma community personally. Sometimes when they need a reality check, a smart first step is a virtual visit. The virtual visits have been one of the things in the past 2-3 years I have enjoyed the most because I can make a big difference in a small amount of time and help other doctors and patients even if they don’t live in Ohio.
That is a huge shift in the way care is administered and are you seeing the benefit?
Dr. Anderson: It has been fun to see how motivated, and not just the patient but their whole family is to help. “Also, the FDA has become more willing to treat and facilitate drug access for children.”
They now have an office called ONC Project Facilitate now where a motivated oncologist, patient, and company can with minimal paperwork get an IND number which allows us to get access to investigational drugs. So, there are more options out there for patients than they know of. What they must do is figure out how to facilitate the process efficiently -and that’s the challenge.
Interview conducted by Ivanhoe Broadcast News.
END OF INTERVIEW
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