Selpercatinib Receives Full FDA Approval to Treat RET-Linked Thyroid Cancer

Giovanna Whitting

Giovanna Whitting received selpercatinib to treat her thyroid cancer as part of a clinical trial when she was 16 years old. Today, she is a healthy, happy college student.

On June 12, 2024, the US Food and Drug Administration (FDA) granted full approval to the targeted therapy selpercatinib (Retevmo®) for treating adult and pediatric patients 2 years and older with advanced or metastatic thyroid cancers that have certain changes in a gene called RET

Selpercatinib had already received accelerated approval from the FDA in 2020 for treating RET-related lung cancer and thyroid cancers in patients 12 and older. Memorial Sloan Kettering Cancer Center (MSK) head and neck medical oncologist Eric Sherman, MD, played a key role in the development of selpercatinib for thyroid cancer. Its approval for lung cancer was based on clinical trials led by thoracic oncologist Alexander Drilon, MD, Chief of MSK’s Early Drug Development Service. 

“Selpercatinib has shown a benefit for the treatment of RET-mutant medullary thyroid cancer compared to older drugs that had been approved for this indication,” Dr. Sherman says. “In addition, it appears to cause fewer severe side effects.”

What Are the Latest Treatment Options for Thyroid Cancer? 

Not all patients with thyroid cancer need targeted therapies like selpercatinib. When these tumors are detected early, they often can be successfully treated with surgery to remove part or all of the thyroid gland, radioactive iodine therapy, or a combination of the two. Some patients may not need these treatments at all, and may instead choose active surveillance, which means the cancer is carefully monitored with scans and other tests. 

But for thyroid cancers that are more advanced or that come back after treatment, selpercatinib provides an important treatment option for cancers linked to the RET gene, Dr. Sherman says. 

How Does the RET Gene Cause Thyroid Cancer? 

Some thyroid cancers have what are called RET fusions. With these changes, part of the gene RET gets rearranged and attaches itself to another gene. That can drive cells to grow out of control and lead to cancer.  

Dr. Eric Sherman

Selpercatinib provides an important treatment option for cancers linked to the RET gene, says Dr. Eric Sherman.

RET fusions are found in about 10 percent of thyroid tumors that originate in follicular cells. This includes anaplastic thyroid cancer, the most aggressive and difficult-to-treat form of the disease. 

Another type of thyroid tumor, called medullary cancer, has a different kind of change to the RET gene. Rather than a fusion, it has a mutation, or change in the gene’s sequence. RET mutations are found in more than half of all medullary thyroid cancers. 

Medullary thyroid cancer is rare and aggressive. It often runs in families, because the RET mutations can be inherited and passed down from parent to child. All people with the inherited form of the disease have the RET mutation.

How Does Selpercatinib Work to Treat Thyroid Cancer? 

 “Selpercatinib works on both types of RET mutations,” Dr. Sherman says. “But at the same time, it’s very specific at blocking the RET protein, and only the RET protein.” 

 He contrasts the effectiveness of selpercatinib with earlier drugs shown to block RET, like cabozantinib (Cometriq®) and vandetanib (Caprelsa®). “Those were what we called ‘dirty’ kinase inhibitors, because they hit a lot of different protein targets,” he explains. “These drugs were sometimes effective, but they had a lot of side effects.” 

“Because selpercatinib is a ‘cleaner’ drug, it works better,” he adds. “And we can give it at higher doses because it typically doesn’t have serious side effects compared to the other drugs” 

How Thyroid Cancer With Other Gene Mutations Are Treated at MSK 

Nonmedullary thyroid cancer (for example, papillary thyroid cancer) may have other gene alterations that can be targeted in a similar fashion with targeted therapies. The most common gene that’s implicated in thyroid cancers is BRAF. Drugs that target BRAF may be used to treat thyroid cancer, either alone or in combination with other drugs. These drugs may also be used in other ways, such as to restore the sensitivity of the thyroid cancer cells to radioactive iodine. 

Additionally, thyroid cancers caused by gene changes called NTRK fusions can be treated with drugs that targeted those mutations. MSK researchers are actively investigating ways to treat other types of mutations or molecular changes that can be found in thyroid cancers as well.

Thanks to MSK-IMPACT®, the molecular test that looks for mutations in more than 500 cancer-related genes, patients can be matched with the best targeted therapies for their cancers. “We use MSK-IMPACT to sequence every advanced thyroid cancer as soon as possible when patients come to us,” Dr. Sherman says. “We’ve learned a lot about the changes that drive these cancers, which will lead to more treatments in the future.” 

Dr. Sherman has provided services to FORE Biotherapeutics (uncompensated), Eisai, Eli Lilly, and Regeneron Pharmaceuticals Inc.