Lenvatinib Treatment for Deadly Thyroid Cancer

Stops tumor progression in refractory, differentiated thyroid cancer


About 1 percent of all malignancies involve the thyroid, and thyroid cancer is 3 times more common in women.  In Western countries with sufficient levels of iodine in food sources, a notable majority of these cancers are a form of differentiated thyroid cancer called papillary thyroid carcinoma. Fortunately, in adults with papillary thyroid carcinoma, distant metastases are less common.

However, distant metastases--which hitch a ride on the circulatory system (hematogenous spread) and hunker down in anatomic sites like lung and bone--are more common with another type of differentiated thyroid cancer called follicular thyroid carcinoma.

Frightfully, such metastases may be a presenting symptom! Unfortunately, some of these people with follicular thyroid carcinoma fail to respond to radiotherapy (radioiodine) after removal of the thyroid. For such patient populations with refractory, differentiated thyroid cancer, the new drug lenvatinib ​(Lenvima) may help. Of note, lenvatinib comes in capsule form.

More about differentiated thyroid cancer

Both papillary and follicular thyroid carcinoma derive from follicular epithelial cells in the thyroid. They are diagnosed by architectural and nuclear differences. Ninety-five percent of thyroid cancers are sporadic with no familial inheritance detected. External radiation is the only proven risk factor for thyroid cancer and differential thyroid cancer--more specifically papillary thyroid cancer--however iodine excess or deficiency may also play a role.

With thyroid cancer, thyroid nodules or "lumps" are a most common presenting symptom.

 Because such nodules are usually "cold" on thyroid scan, fine needle aspiration (a type of biopsy) is a good way to diagnoses these tumors.

Differentiated thyroid cancer is first treated with surgery, the extent of which--radical or conservative--is controversial and depends on involvement of both the thyroid and lymph nodes.

 In cases of follicular thyroid cancer that is widely invasive (distant metastases), the entire thyroid must be removed in order for radioiodine to take.

Of note, follicular thyroid cancer is most common in people in their 50s and 60s, and once it metastasizes, 10-year survival rate is 10 percent. (Overall, in 2014, 1,890 people in the United States died of thyroid cancer as a whole.)  Moreover, chemotherapy has yet to be proven effective in those with differentiated thyroid carcinoma.

More about lenvatinib

Without getting too specific, lenvatinib is a multitargeting tyrosine kinase inhibitor that inhibits molecular pathways involved in tumor growth and maintenance. In other words, lenvatinib inhibits the growth of tumor cells distant from the thyroid which have defied treatment with radioactive iodine.

In February 2015 after reviewing results from a Phase 3 clinical trial, the FDA approved lenvatinib. Researchers examined 392 people with differentiated thyroid cancer that was refractory to radioiodine.

  More specifically, lenvatinib was administered to 261 participants while 131 participants received placebo. Importantly, this study was designed with a crossover which enabled people with disease progression to switch from placebo to lenvatinib. Because of such crossover, researchers were unable to tease out whether lenvatinib increased overall survival time.

Researchers were, however, able to prove that the median progression-free survival was 18.3 months in the experimental group or those receiving lenvatinib versus 3.6 months in those in the control group who received placebo.

Forty percent of participants taking lenvatinib did experience adverse effects which, in most cases, were controlled by adjusting dosage of the drug. Nevertheless, 14.2 percent of participants taking lenvatinib dropped out of the study, and 6 of 20 deaths that occurred during the study's 14-month span were considered attributable to the drug.

Specifically, here are some of lenvatinib's adverse effects:

  • hypertension (67.8 percent of participants)
  • diarrhea (59.4 percent of participants) 
  • fatigue (59 percent of participants)
  • decreased appetite (50.2 percent of participants)
  • decreased weight (46.4 percent of participants)
  • nausea (41.0 percent of participants)

Overall, results from this trial suggest that in those with deadly differentiated thyroid cancer that is resistant to radiotherapy, lenvatinib may stop the cancer's deadly progression. If you or a loved one is suffering from such deadly disease, findings of this study are encouraging. However, more research needs to be done in order to figure out exactly who needs the drug, what dosages are most effective, and whether stopping progression leads to better quality of life. After all, even the most effective treatments mean little if your quality of life is terrible.

Selected Sources

Book chapter titled "Differentiated thyroid carcinoma" by O. Gimm and H. Dralle from Surgical Treatment: Evidence-Based and Problem-Oriented published in 2001.  Accessed from NCBI Bookshelf on 3/5/2015.

Article titled "Lenvatinib improves survival in refractory thyroid cancer" by S Mayer from The Lancet published in 2015.  Accessed on 3/5/2015.

Article titled "Extent of Surgery for Differentiated Thyroid Cancer: Recommended Guideline" by GA Rahman from Oman Medical Journal published in 2011  Accessed on 3/6/2015.

Article titled "Lenvatinib versus Placebo in Radioiodine Refractory Thyroid Cancer" by M Shlumberger and co-authors from NEJM published in 2015.  Accessed on 3/5/2015.

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