Eric J. Sherman, MD, Head and Neck Oncology Service, Memorial Sloan-Kettering Cancer Center, discusses a pilot study of selumetinib-enhanced radioiodine uptake in advanced thyroid cancer.

This study was conducted to determine whether selumetinib could reverse refractoriness to radioiodine in patients with metastatic thyroid cancer. An  iodine-124 positron-emission tomography (I-124 PET scan) was performed before and after selumetinib administration (75 mg twice daily). Sherman says that an I-124 PET scan is an adequate way of measuring change objectively in each lesion.

In the study, 12 patients had an increase in radioactive iodine in their tumors. Eight (of the 12) patients had a significant enough uptake to be treated with radioactive iodine. Sherman believes the data from this pilot study could benefit patients with early disease.

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Dr. Sherman on Selumetinib-Enhanced Radioiodine Uptake 

Eric J. Sherman, MD, Head and Neck Oncology Service, Memorial Sloan-Kettering Cancer Center, discusses the treatment of anaplastic thyroid cancer with intensity-modulated radiation therapy, paclitaxel, and pazopanib.

Anaplastic thyroid cancer is a large area of unmet need, Sherman says, as survival is typically less than six months. A phase II trial is examining the addition of pazopanib, a tyrosine kinase inhibitor, to radiation therapy and paclitaxel in patients with locally advanced anaplastic thyroid cancer or diseases that are metastatic elsewhere. Pazopanib has shown good response in differentiated thyroid cancer, but not in anaplastic thyroid cancer.

The idea behind this new combination is that adding pazopanib to a taxane will increase its benefit and that controlling the disease in the neck will lead to long term benefit. These drugs and radiation have not been used together before and toxicity must be controlled. Sherman says that although this is a phase II trial, overall survival is the primary outcome.

Eric J. Sherman, MD, Head and Neck Oncology Service, Memorial Sloan-Kettering Cancer Center, discusses the treatment of anaplastic thyroid cancer with intensity-modulated radiation therapy (IMRT), paclitaxel, and pazopanib.

Dr. Sherman on Pazopanib in Anaplastic Thyroid Cancer

Eric J. Sherman, MD, Head and Neck Oncology Service, Memorial Sloan-Kettering Cancer Center, discusses the current evidence that is available on the optimal sequencing of vandetanib (Caprelsa) and cabozantinib (XL184) for patients with medullary thyroid cancer (MTC).

Results on the administration of cabozantinib for patients with MTC, from the phase III randomized EXAM trial, were presented at the ASCO annual meeting in June and were the basis for submission to the FDA. This trial showed a significant increase in progression-free survival for cabozantinib over placebo. The trial was designed to allow for an overall survival endpoint; however, data for this endpoint is not yet mature.

Evidence on the exact sequencing of cabozantinib and vandetanib is still early and vague and at this point it is unclear how the two agents should be sequenced, Sherman believes. Evidence from the EXAM trial showed that cabozantinib is effective after progression on vandetanib; however, no evidence is available on the effects of using cabozantinib first.

Dr. Eric Sherman, Memorial Sloan-Kettering Cancer Center, on the optimal sequencing of cabozantinib and vandetanib for patients with medullary thyroid cancer.

Dr. Sherman on Sequencing Cabozantinib and Vandetanib

Eric J. Sherman, MD, Head and Neck Oncology, Memorial Sloan-Kettering Cancer Center, discusses two of the leading concerns for the oral kinase inhibitor vandetanib (Caprelsa), an FDA approved treatment for medullary thyroid cancer.

Following the positive results that eventually led to the approval of vandetanib the FDA expressed two main concerns over the possible side effects and dosing strategy for the agent.

The first concern was over QTc interval prolongation, which may lead to cardiac events. Despite this concern, few patients on the vandetanib trial actually experienced this type of adverse reaction. The possibility of cardiac events led the FDA to require certification before the agent could be prescribed. Sherman notes, the registration process involves a short online course describing recommendations, monitoring, and when to discontinue or adjust therapy.

Secondly, the FDA expressed concerns over the starting dose of 300 mg per day, which was used in the trial and was shown to increase progression-free survival to 22.6 months compared with 16.4 months for placebo. This concern was further substantiated by another phase II trial investigating vandetanib that used a 200 mg daily dose; this trial demonstrated similar positive results.

A 300 mg a day initial dose of vandetanib is currently approved by the FDA with the recommendation to reduce the dose to 200 mg for patients with moderate to severe renal impairment or dose modifications for severe toxicities.

Dr. Eric Sherman, from Memorial Sloan-Kettering Cancer Center, Discusses Vandetanib's Dosage and Precautions

Dr. Sherman on Vandetanib's Dosage and Precautions

Eric J. Sherman, MD, Head and Neck Oncology Service, Memorial Sloan-Kettering Cancer Center, discusses the phase III clinical trial that investigated vandetanib (Caprelsa) a tyrosine kinase inhibitor that is now approved by the FDA for the treatment of symptomatic or progressive medullary thyroid cancer in patients with unresectable locally advanced or metastatic disease.

The randomized phase III study compared vandetanib to placebo. If patients receiving the placebo progressed while on the first-line treatment they were allowed to crossover to the vandetanib arm of the trial. Patients receiving vandetanib saw an increase in progression-free survival but an overall survival (OS) benefit was not demonstrated. The lack of an OS benefit can be contributed to the design and crossover within the trial.

The drug elicited a higher than expected response rate and improved the quality-of-life for patients with symptomatic medullary thyroid cancer.

Dr. Eric Sherman from Memorial Sloan-Kettering Cancer Center Discusses the Vandetanib Trial

Eric J. Sherman, MD

Articles

Dr. Sherman on Selumetinib-Enhanced Radioiodine Uptake

Dr. Sherman on Pazopanib in Anaplastic Thyroid Cancer

Dr. Sherman on Sequencing Cabozantinib and Vandetanib

Dr. Sherman on Vandetanib's Dosage and Precautions

Dr. Sherman Discusses the Vandetanib Trial