Thyroid cancer is the 18th most common cancer among women in Europe. There were over 2,700 new cases of thyroid cancer in the UK in 2011 and it is growing by about 100 new cases each year. In 2012 there were 371 deaths from thyroid cancer in the UK. (Statistics from Cancer Research UK.)
Most types of thyroid cancer are highly treatable. Even in more complex cases, the outlook is brighter than for some common cancers and it is possible to live for longer with advanced thyroid cancer and enjoy a good quality of life. However, sometimes the usual therapies may no longer work. Until recently, the options for treating advanced thyroid cancer were limited. Now, however, there is a new class of targeted therapies emerging. These include tyrosine kinase inhibitors (TKIs).
There are currently no licensed targeted therapies for use in thyroid cancer but this is expected to change. Examples include the TKIs sorafenib, vandetanib, cabozantinib and lenvatinib.
What are targeted therapies?
Targeted therapies aim to block cancer cells by interfering with specific molecules in the cells that make them grow and divide, while doing little damage to normal cells. Traditional chemotherapy aims to stop the growth of cancer cells by blocking all rapidly dividing cells.
What are tyrosine kinase inhibitors (TKIs)?
Tyrosine kinase inhibitors (TKIs) are a type of targeted therapy. They inhibit (block) chemical messengers called tyrosine kinases in cancer cells. Blocking these messengers stops the cell from growing and dividing. They are used in the treatment of several types of cancer including liver and kidney cancer as well as thyroid cancer.
Which types of thyroid cancer may be treated with TKI drugs?
Treatment with a TKI may be an option for some types of advanced thyroid cancer, such as differentiated thyroid cancer (papillary and follicular thyroid cancer) that is resistant to radioactive iodine; and metastatic, progressive medullary thyroid cancer.
What is radioiodine refractory differentiated thyroid cancer (RR-DTC)?
Differentiated thyroid cancer is usually treated with surgery and, in some cases, by one or more doses of radioactive iodine (RAI). This is effective in treating most patients. In a small number of cases, however, the thyroid cancer cells lose their ability to take up RAI and therefore the iodine cannot kill off the cancer cells. If this has happened, further RAI treatment won't be of any benefit. This is sometimes called non-RAI-avid disease or RAI refractory disease or 'radioiodine refractory differentiated thyroid cancer' (RR-DTC). In some cases treatment with a TKI may be an option.
Q. What is advanced medullary thyroid cancer?
Patients with medullary thyroid cancer (MTC) are usually treated with total thyroidectomy and may be offered external beam radiation for locally recurrent tumours. Often the disease is confined to the neck. In a small number of cases it spreads beyond the neck. Treatment with a TKI may be an option if the disease has spread outside the thyroid gland and cannot be removed with surgery. RAI has no place in the treatment of MTC.
How do I know if I may need treatment with a TKI?
If your thyroid cancer is progressing, your doctor may discuss other options with you, which may include additional surgery, a repeat dose of radioactive iodine, or in some cases a TKI. Your doctor may also talk to you about any available clinical trials that may be suitable for your situation. Treatment with a TKI is not always appropriate, it will depend on a number of factors including any other medical conditions you may have and how well you feel. If you have any questions about your treatment options do not hesitate to ask your doctor.
What are the main TKI drugs used in the treatment of advanced thyroid cancer in the UK?
TKIs for the treatment of thyroid cancer include:
Sorafenib (Nexavar) has been approved for the treatment of locally advanced or metastatic patients with radioactive iodine-refractory differentiated thyroid cancer. It is available in England via the Cancer Drugs Fund.
Vandetanib (Calpresa) has been approved for the treatment of progressive medullary thyroid cancer. It is available in England via the Cancer Drugs Fund.
Cabozantinib (Cometriq) has been approved for the treatment of progressive medullary thyroid cancer. It is available in England via the Cancer Drugs Fund. It has also recently been approved for use in Wales.
Lenvatinib (Lenvima) has been approved by the Food and Drug Administration (FDA) in the USA and has been submitted to the European Medicines Agency (EMA) for approval. It is not yet available in the UK except via clinical trials. Other TKIs such as selunetemib are undergoing clinical trials in the UK.
What are the side effects?
Some of the most common side effects of TKIs are:
- Loss of appetite
- Nausea or vomiting
- Hypertension (raised blood pressure)
- Hand-foot syndrome (sore and red palms of the hands and soles of the feet)
Not everyone experiences these side effects or to the same degree. They may vary according to the type of TKI being taken. If you are taking a TKI it is important you discuss any side effects with your doctor as there may be ways to manage these. Sometimes it is possible to relieve these effects by changing the dose, or by switching to another TKI.
How is TKI treatment paid for?
All drugs need a licence before doctors can prescribe them on the NHS. After approval by the EMA, new drugs still need to be submitted to the Medicines Healthcare Products Regulatory Agency (MHRA) which assessed and authorises new drugs, and the National Institute for Health and Care Excellence (NICE) which decides which drugs and treatments are available on the NHS in England and Wales.
Decisions on which drugs to licence in Wales and Scotland are made separately by the respective bodies: the All Wales Therapeutics and Toxicology Centre and the Scottish Medicines Consortium. Cabozantinib has recently been approved for use for advanced MTC in Wales although it has been declined in Scotland.
In England, some of drugs that are under submission to MHRA and/or NICE are paid out of the Cancer Drugs Fund (CDF).
What is the Cancer Drugs Fund?
The Cancer Drugs Fund was established in 2010 to enable patients to access drugs that are not routinely available through NHS England.
There is a single, national list of drugs and indications that the CDF will routinely fund and standard operating procedures for administration of the fund. Applications to the fund must be made on behalf of patients by a recognised and accredited cancer specialist and must be supported by the NHS trust/foundation trust's clinical cancer lead.
How can I find out about clinical trials?
Cancer Research UK maintains a clinical trials database which aims to list all cancer trials and studies in the UK.
For more information see: Cancer Research - Clinical Trials
Clinical Trials in the UK Jennifer A. Sipos, Manisha H. Shah
Ther Adv Med Oncol. 2011;2(1):3-16.