Clinical trial enrollment must become speedier for patients with rare diseases such as anaplastic thyroid cancer, says Maria Cabanillas, M.D.
In rare diseases with limited populations — like anaplastic thyroid cancer — finding and enrolling in a clinical process can be a long and difficult process for patients, says Maria Cabanillas, M.D.
“We need to work very hard to speed this up because these patients need effective therapies, and they need them now,” says Cabanillas, associate professor, department of Endocrine Neoplasia and Hormonal Disorders, Division of Internal Medicine, The University of Texas MD Anderson Cancer Center.
“We have a lot of patients that never even have the opportunity to come in and visit with an anaplastic thyroid cancer expert to determine if they should be enrolled on a clinical trial or be put on a targeted therapy outside of the trial, because the doctors at home tell them that there is no hope and they need to go to hospice. We need to change that.”
To make sure patients with anaplastic thyroid cancer receive effective therapy as quickly as possible, Cabanillas and her colleagues initiated a program called Facilitating Anaplastic Thyroid Cancer Specialized Treatment (FAST). This program coordinates with administrative and clinical staff to ensure that patients with anaplastic thyroid cancer are identified and given rapid access to care. It has improved the average referral-to-disposition for patients with anaplastic thyroid cancer to half a day.
What is the potential for immunotherapy in anaplastic thyroid cancer?
In addition to speeding up the process, new more effective treatments need to be explored, says Cabanillas. Immunotherapy has potential, but it presents a challenge because of the length of time it takes to have an effect. In an interview with CURE, Cabanillas discussed an upcoming clinical trial she is involved in that is combining immunotherapy with targeted therapy, that may offer a solution. She also discusses the challenges that still remain regarding the diagnosis of anaplastic thyroid cancer and what she sees on the horizon.I think immunotherapy in anaplastic thyroid cancer is going to be a challenge, but it is going to be a very good treatment for patients. The trick is to design trials that are going to be successful, knowing that anaplastic thyroid cancer is a very rapidly progressing, aggressive type of thyroid cancer and patients really need to get a response within weeks; they can’t wait months. Immunotherapy usually does take on average 3 or 4 months before it really starts to take effect. These patients don’t have that kind of time.
If we design the trials correctly, knowing this disease very well, we will be successful. Our idea in the study that we’ve designed and we’ve been funded for, is a trial using targeted therapy in conjunction with immunotherapy. The trial will start out by determining what the molecular mutations are in these patients’ tumors, and then they will be assigned a treatment cohort that will include immunotherapy plus the targeted therapy.
What is the status of this trial?
I think that is the way to go for two reasons. One, the targeted therapy buys you some time before the immunotherapy starts to work. That is really what these patients need. Two, we may actually be able to improve the efficacy of immunotherapy by using targeted therapy. This has been shown in a number of different malignancies, including in melanoma, where a BRAF and a MEK inhibitor were shown to improve the effect of the immunotherapy. Right now this trial is written, it has been vetted by the sponsor, and we have a commitment of funding. We anticipate that we will probably start the trial sometime in early 2017. This trial will look at anaplastic thyroid cancer and poorly differentiated thyroid cancer, but its only at MD Anderson.
What do you see on the horizon in the next 10 years for anaplastic thyroid cancer, and what do we need to do to get there?
Our primary focus is to learn how this approach of combining immunotherapy and targeted therapy is going to work in anaplastic thyroid cancer, but we want to get some preliminary data on poorly differentiated thyroid cancer. There are some poorly differentiated thyroid cancers that behave more like anaplastic thyroid cancer.I’ve thought about this question a lot over the past several years. I saw that we are making these great strides in differentiated and medullary thyroid cancer, but there was not much in terms of advancing the field in anaplastic thyroid cancer. Our endpoint is essentially to cure this disease. To achieve this, we started out by thinking about how to enroll these trials. It is very difficult to enroll anaplastic thyroid cancer trials because it’s such a rare tumor and they are elderly patients and they have a lot of different medical problems that they present with. It is a rapidly progressing disease and patients die quickly without any treatment.
What we did at MD Anderson is put together a group of physicians from many different specialties who were interested in seeing these patients and were committed to adding these patients into their clinics very quickly, so we could get them into the system quickly. You don’t have 2, 3 weeks to wait when you have anaplastic thyroid cancer, you need to be seen quickly. We did a quality improvement project where we actually sped that up and got these patients in very quickly.
What we see is that we went from seeing 16 new anaplastic thyroid cancer patients a year in 2012, to a projected of 60 this year. Part of the reason that we have not made progress is because we haven’t been able to enroll the trials. This is one way to speed that up, enroll the trials, and hopefully answer the question quickly of whether this particular treatment is going to work or not, rather than having a study open for five years and finding out that it doesn’t work. We want to know quickly if that works and move on to the next treatment. That is how you can advance the field quickly. I think in 10 years we will actually will have FDA-approved therapies for anaplastic thyroid cancer. I foresee that happening in the next five years.
How is someone diagnosed with anaplastic thyroid cancer, and are there any challenges with that?
We are doing a clinical trial that is opening soon with lenvatinib in anaplastic thyroid cancer. We also have a trial with Tafinlar (dabrafenib) plus Mekinist (trametinib) in anaplastic thyroid cancer. Those we hope to have some favorable outcomes and hopefully one of those two will be approved for this disease. In 10 years I think we are going to know if immunotherapy is an effective therapy and hopefully we will have an approved immunotherapy.The first step is recognizing that something is very wrong. If a patient has a rapidly growing thyroid mass or any mass in the neck, that patient immediately needs to have a biopsy and an ultrasound. If it is suspected that the patient has a thyroid cancer and it is growing that rapidly, that patient’s referral to a center of expertise needs to be expedited.
Anaplastic thyroid cancer is somewhat of a difficult diagnosis to make pathologically, so we like for our thyroid pathologists to review these patients to make sure the diagnosis is correct before we commit a patient to a certain treatment that might not be accurate. For example, anaplastic thyroid cancer can be confused with lymphoma of the thyroid, which has a completely different treatment and a completely different prognosis. We want to be sure they don’t have lymphoma. They can also be confused we metastasis from another organ, such as renal cell carcinoma, breast cancer, or lung cancer. You want to get the diagnosis right.
Once that is confirmed, the patient should really be referred to a center with expertise in anaplastic thyroid cancer to determine if they can be added to a clinical trial and what therapy might be best for them. Then we go from there.