Vandetanib is approved in the US for medullary thyroid cancer

About 44,600 new cases of thyroid cancer were diagnosed in the US last year, with about 1,690 of those resulting in death, according to the US National Cancer Institute. Medullary thyroid cancer is estimated to represent up to 5% of all thyroid cancers, with about 2,200 patients being diagnosed last year with that form of the disease.

Multi-targeted tyrosine kinase inhibitors dominate the thyroid cancer pipeline (see: Pipeline Insight: Cancer Overview Malignant Melanoma, Neuroendocrine Tumors and Thyroid Cancer). There are four late-stage drugs which are forecast to achieve sales of $97m by 2019. It has long been thought likely that at least one of the late-stage drugs will be the first agent approved specifically for medullary thyroid cancer.

Likelihood has now become reality as the FDA has approved orphan drug vandetanib for the treatment of thyroid cancer.

The safety and effectiveness of AstraZeneca's vandetanib were established in a single, 331-patient randomized international Phase III ZETA study designed to measure progression free survival in patients with late-stage medullary thyroid cancer.

The results showed a median PFS of 16.4 months in the placebo arm and at least 22.6 months in the vandetanib arm. Final progression-free survival in patients treated with vandetanib has yet to be disclosed; moreover, overall survival data re not currently available.

Despite these two issues, vandetanibdoes represent an advance in the treatment of thyroid cancer, but not without a price. Vandetanib's labeling comes with a black-box warning of QT prolongation, torsades de pointes and sudden death. Because of those risks, AstraZeneca was required to implement a risk evaluation and mitigation strategy (REMS) plan for vandetanib,.

While the majority of medullary thyroid cancer cases are sporadic, approximately 20% to 25% are hereditary, caused by inherited mutations in the RET proto-oncogene, which drives the growth of malignant cells. Approximately 25-60% of sporadic MTCs have a somatic mutation of the gene as well.

Vandetanib inhibits RET, as well EGFR and VEGFR, which are involved in cell proliferation and angiogenesis in a number of different tumour types.

Vandetanib is also in Phase II development for the common forms of thyroid cancer (follicular and papillary).