Memorial Sloan-Kettering Cancer Center (US): Selumetinib in thyroid cancer

Dr. James A. Fagin, Chief of the Endocrinology Service at Memorial Sloan-Kettering Cancer Center in New York City, has pioneered research in cells, mice and most recently a clinical study that could lead to a new treatment option for patients with thyroid cancer.

Many patients with advanced thyroid cancer have tumours that are difficult to treat because they are unable to absorb radioactive iodine, the most effective therapy for this disease. Dr. Fagin, together with Dr. Alan Ho and other colleagues, designed and ran a Phase II investigator-sponsored clinical study under a Cooperative Research and Development Agreement (CRADA) with the National Cancer Institute (NCI) in the US. This pilot study showed that an investigational drug called selumetinib can reverse radioiodine resistance in some patients with advanced thyroid cancer, leading to radioiodine uptake, tumour shrinkage and clinical responses. Re-incorporation of radioiodine, a proven standard of care, would not be possible without selumetinib pre-treatment in these cases. The clinical results were presented at ASCO 2012 and published in the New England Journal of Medicine in February 2013.

The results of this pilot investigator-sponsored study resulted in AstraZeneca opening a larger randomized clinical study of registration-intent. This study is now recruiting newly diagnosed patients with differentiated thyroid cancer at high risk of primary treatment failure. The opportunity to intervene earlier in the cancer disease process may lead to higher remission rates, which in turn may prevent thyroid cancer from spreading and becoming more advanced. This study is due to read out in March 2019. AstraZeneca are also actively engaged in supporting new clinical opportunities for selumetinib in advanced thyroid cancer, to build on the data from Dr. Ho’s pilot study.

This investigation into a new patient treatment strategy would not have been possible without the close collaboration between AstraZeneca and the investigators at Memorial Sloan-Kettering.

MSKCC blog article: Drug Reverses Radioiodine Resistance in Some People with Advanced Thyroid Cancer

Selumetinib (AZD6244, ARRY-142886) is a potent and selective MEK1/2 inhibitor. In August 2016, AstraZeneca announced results from the Phase III SELECT-1 trial of the MEK 1/2 inhibitor, selumetinib, in combination with docetaxel chemotherapy as 2nd-line treatment in patients with KRAS mutation-positive (KRASm) locally-advanced or metastatic non-small cell lung cancer (NSCLC).