Arun Singh, MD: The title of today’s webinar is Understanding Your GIST Journey and how QINLOCK, otherwise known as ripretinib, may be able to help. We will be discussing information about GIST and its treatment, which will include taking a close look at QINLOCK, a prescription medicine used to treat adults with GIST who have received 3 or more prior therapies for their disease.
Today, I am joined by Sandra Brackert, who is a nurse practitioner in the UCLA Sarcoma Program. She has extensive experience in taking care of patients with GIST and sarcomas.
Sandra Brackert, NP: Hi, my name is Sandra Brackert, and I’m a nurse practitioner at UCLA in the Sarcoma Program. I’ve been there since 2008, and we specialize in treating patients with GIST, or gastrointestinal stromal tumors. Some of you may go to what’s called a gastroenterologist for treatment, but at UCLA, in the Sarcoma Program, we specialize in treating GIST patients.
Arun Singh, MD: My name is Arun Singh. I’m a medical oncologist at UCLA. I specialize in taking care of patients with GIST and sarcomas. Today, we’re going to discuss some of the basics of GIST, and we’re going to learn a little bit more about this disease and its challenges.
We’re going to talk about some of the treatment options for advanced GIST. We will also talk about the use of QINLOCK, otherwise known as ripretinib. QINLOCK is a different type of tyrosine kinase inhibitor, or TKI for short, designed to treat adults with advanced GIST who have received 3 or more prior lines of treatment for their disease. QINLOCK was approved in 2020.
We’re also going to highlight some of the services and resources to help you on your GIST journey. We’re going to stop periodically to answer some commonly asked questions about this disease and to explain some of the common terms.
It’s important to give you a vocabulary to empower you and to be more knowledgeable about what’s going on with your cancer.
What is GIST?
GIST stands for gastrointestinal stromal tumor. There are about 4,000 to 6,000 cases of GIST per year in the United States; however, the cause of this disease is unknown. There are no known lifestyle factors, such as diet or smoking, that are associated with this disease. The median age of diagnosis is about 60 years old, and it affects men and women approximately equally.
This disease can start anywhere in the GI tract, including the esophagus, stomach, small intestine, colon, and even the rectum. Rarely, GIST can start outside the GI tract, but those are very uncommon situations.
So, how do I evaluate patients with newly diagnosed GIST? There are 2 main things. One, it’s important to test the tumor and look at it under the microscope. It’s important to determine that you actually have GIST and not another type of cancer or sarcoma.
The test will also give us information about how aggressive your GIST is. And this will be used by your oncologist to inform about your treatment. Two, we also need really good imaging to have a clear picture of the tumor and where it is. This will help us determine if the GIST is in 1 location. If it’s in 1 location and it can be removed by surgery, the term for that is “resectable GIST”.
In many cases, GISTs in multiple locations are not resectable. If there are multiple GISTs that affect several organs and if the person has health issues, that can make surgery risky. Also, surgery might not be the best option if the GIST is very large.
Next term is “advanced GIST”. Advanced GIST is defined as GIST that can no longer be treated with surgery alone, or has come back—otherwise known as “recurrent GIST”. We also use the term “metastatic GIST” for GIST that has spread.
GIST is something that you may be living with for a very long time. And, if you have developed advanced GIST, treatment options and needs change over time.
The other thing that’s important are gene mutations and how they impact the outcomes of this disease, as well as the treatment options that are available. That’s what we’re going to discuss next.
Gene mutations and how they affect GIST.
GIST happens when the genes of our body change. Genes make proteins that control how cells work, and mutated genes can cause cells to multiply uncontrollably and become cancerous. Many people have normal genes that we talk about, such as KIT or PDGFRα. And several thousand other genes as well.
However, in GIST, these normal genes, KIT or PDGFRα, have changed or become corrupted, and the term that we use for that change is a “mutation”. These mutations are like “on” switches. It tells a protein called a tyrosine kinase to be on all the time. And this leads to uncontrolled [cell] growth or “proliferations”, the medical term for that, leading to cancer.
We subdivide the mutations into primary or secondary mutations. Primary mutations are the ones that we feel are responsible for starting the growth of GIST tumors. In people with GIST, the most common primary mutations are KIT mutations, in about 70% to 80% of cases.
PDGFRα mutations are found in about 5% to 10% of cases. The other 10% to 15% of mutations are known as wild-type GIST, in which no KIT or PDGFRα mutations are found.
Over time, genes can continue to mutate. These new mutations are called secondary mutations. Secondary mutations can lead to drug resistance. The most common secondary gene mutations in people with GIST are in KIT and PDGFRα, as we’ve mentioned earlier.
Doctors often test for gene mutations found in GIST tumors. Gene mutation testing essentially is taking a piece of your tumor, extracting DNA or RNA from it, and running it on what is called a gene-sequencing machine.
Sometimes we can also do something called “immunohistochemistry”, which is doing special stains on your tumor to see if there are individual proteins present or absent in your particular GIST. Knowing the specific mutation type may help your doctor choose a treatment for you, and it can also help change the dose of the drug that you’re receiving. It’s a really good way to help tailor your treatment.
So, some common questions from people with GIST…
One…
Q: Why did my doctor do my mutation testing twice?
A: There are a few reasons that this may be the case. Over time, your disease can change. That’s because the mutations can change over time. And, for some patients who are developing secondary mutations, it can be important to recheck and to document the new mutations to understand why you may or may not still be responding to therapy.
Also, some patients have multiple deposits of GIST in their abdomen and pelvis. These spots can be different genetically. If you only biopsy one spot, you may not know what’s happening in the other spots, and you only have information on the individual biopsy. Sometimes we can repeat mutation testing if new biopsies are present.
A second question is….
Q: Can different tumors have different mutations?
A: As we discussed, over time, mutations can change; and, for patients who are developing secondary mutations, it can then be important to recheck and to document, to understand why you may or may not still be responding to therapy. The answer is absolutely “yes”—different tumors can have different mutations.
Q: A third question is, the results of my mutation testing included an exon number. What is an exon?
A: An exon is an expressed part of your gene. Further detailed, there are several exons in KIT; for instance, each individual exon can have mutations.
Another way to think about an exon is like a train track or train line. There are different stops on the train line, and the exon number helps to detail exactly where the mutation is.
In GIST, mutations can switch 'on' a kind of protein in the body called a tyrosine . A tyrosine kinase with a mutation is like a light switch that’s stuck in the ‘ON’ position. It sends signals that make cancer cells grow and spread uncontrollably.
