Targeted Therapy Shows Benefit in Rare Type of Thyroid Cancer

Adapted from the NCI Cancer Bulletin.

Treatment with the multitargeted agent vandetanib (Caprelsa®) improved progression-free survival in patients with medullary thyroid cancer (MTC), according to findings from a randomized clinical trial. Earlier this year, the Food and Drug Administration (FDA) approved vandetanib for the treatment of patients with MTC based on initial findings from the phase III trial. MTC is a rare cancer, accounting for only 5 percent of all thyroid cancer cases, and radiation and chemotherapy have limited effects once the cancer progresses to an advanced stage.

The trial's results were published online October 24, 2011 in the Journal of Clinical Oncology.

At 24 months of follow-up, median progression-free survival had not yet been reached for patients who received vandetanib, reported Samuel Wells, M.D., of the Medical Oncology Branch in NCI's Center for Cancer Research and his colleagues. Estimated progression-free survival for the patients treated with vandetanib was 30.5 months, compared with 19.3 months for patients who received a placebo.

The double-blinded trial enrolled 331 patients with MTC who were randomly assigned to receive vandetanib or a placebo. All patients had locally advanced disease or distant metastases. If there was evidence that their disease was progressing, patients in the placebo arm could opt to receive open-label vandetanib.

In addition to the improvement in progression-free survival, the objective response rate was higher and several other disease-related measures were better in the vandetanib arm than in the placebo arm. One of the drug's targets is RET kinase, and the measurable response rate appeared to be higher in patients with RET mutations than in those without mutations. Because so few patients were defined as not having a RET mutation, the response rate in RET mutation-negative patients remains uncertain.

Because 52 patients in the placebo arm received open-label vandetanib, the authors explained, it may not be possible for the trial to show an improvement in overall survival.

A number of side effects were more common in patients who received vandetanib, including diarrhea, nausea, and hypertension; 12 percent of patients stopped taking the drug because of side effects.

Vandetanib's side-effect profile should influence which patients with MTC receive the drug, wrote Benjamin Solomon, M.B.B.S., Ph.D., and Danny Rischin, M.D., of the Peter MacCallum Cancer Center in Australia in an accompanying editorial. The 8 percent of patients treated with vandetanib who had QTc prolongation, a type of heart rhythm disturbance, is "particularly concerning," they continued. Because of the risk of QTc prolongation, vandetanib is only available under a Risk Evaluation and Mitigation Strategy.

Patients with advanced MTC who are not exhibiting symptoms should simply be monitored for evidence of disease progression, Drs. Solomon and Rischin advised. "In contrast, patients who are symptomatic, have a high disease burden, or have rapidly progressing disease stand to benefit the most from treatment with vandetanib."