New FDA Approval: Lenvatinib

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Lenvatinib skeletal



Lenvatinib [Lenvima]


Locally recurrent or metastatic, progressive, radioactive iodine-refractory differentiated thyroid cancer

I’m sorry, what in the heck did you just say?

Lenvatinib can be used to treat the vast majority of thyroid cancers (differentiated thyroid cancers account for about 94% of all thyroid carcinomas according to NCCN)--after they have failed radiation therapy.

How it works:

Inhibits multiple receptor tyrosine kinases (RTKs). Some of these include VEGF, FGF, and PDGF. This is not a cell biology textbook, so look elsewhere for further details on RTKs. Suffice it to say, lenvatinib shuts down several signaling pathways used by the tumor cell. The downstream effects include decreases in angiogenesis, tumor growth, and cancer progression.

Notable Adverse Events:

Like other drugs that impact VEGF (eg. bevacizumab [Avastin]), there is a risk of hypertension, GI perforation/fistula, and proteinuria. With VEGF inhibition, you also have to worry about both thrombotic and hemorrhagic events. These are significant enough that many institutions have a built in monitoring protocol including blood pressure and urinalysis required before administering the drug.

Lenvatinib also adds in the complications of heart failure, QT prolongation, hypocalcemia, and both liver and kidney damage.

Lest you think you’re out of the woods after all of that, lenvatinib displays embryofetal toxicity (thyroid carcinoma is several times more common in women than men, and it absolutely can present during childbearing years).

Current Place in therapy:

Systemic chemotherapy is pretty much used as a last resort for thyroid carcinoma. In general, your steps of therapy are as follows:

  1. Surgical removal

  2. Radioactive iodine

  3. External beam radiation

  4. Systemic chemotherapy-----> Lenvatinib is here

There actually aren't many other systemic drugs used for thyroid cancer (the agents used include Sorafenib [Nexavar], Cabozantinib [Cometriq], and Vandetanib [Caprelsa]). Agents approved for other tumors (ex. Sunitinib [Sutent]) and several investigational drugs are also being looked at.

Also, we should briefly mention that thyroid supplementation (ie. levothyroxine or similar) will be required for basically every thyroid carcinoma. Whether we remove the thyroid surgically or render it useless with radiation/chemo, patients cannot last long without thyroid activity. 

Do you want an Oncology Cheat Sheet? 

It's got all you need to know for the NAPLEX. It's a great way to prepare for an APPE rotation. Keep it on hand when you're practicing and you'll know what to monitor. 

It packs a ton of information in a single page. Dose limiting toxicities, renal and hepatic dosage adjustments, emetogenic potential, likelihood of hair loss, infusion reactions, and much more. 

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