Pharma Strategy Blog

Medullary thyroid cancer is difficult to treat, but recent results with a compound known as XL184 have shown some early and encouraging responses.  They were reported at the EORTC-NCI-AACR meeting in Geneva last week.  XL184 (Exelixis), targets cell growth and migration, as well as blood vessel growth (angiogenesis), through inhibition of MET kinase, VEGFR and RET kinase.

In a phase I study, 84 patients with a variety of advanced tumours that were not amenable to standard therapy were administered XL184 for either the first five days of a 14-day cycle or daily throughout the cycle. The group included 36 patients with advanced medullary thyroid cancer, for which no treatment is known to work.  Response to the drug was assessed at 28 days and subsequently every eight weeks. 

The impact on tumour shrinkage was noticeable in the medullary thyroid cancer patients, where the overall disease control rate (ie the percentage of patients with either a partial response to the drug or prolonged stable disease for more than three months) was an amazing 84% in the 25 patients who have been followed for at least three months.

In addition, partial response, where tumours shrink by at least 30%, was achieved in 55% of the 22 patients with measurable disease who have been followed for at least three months. Most of the others experienced prolonged stable disease beyond three months, and for most of these patients there was actually tumour shrinkage.

Three of the medullary thyroid cancer patients had unmeasurable disease. Tumour biomarkers such as plasma calcitonin and CEA dropped significantly after therapy in most of the patients.

Of the 84 patients, including patients with diverse cancers, disease stabilisation for at least three months was seen in 28 cases. In 16 of those cases, the disease was stable for six months or more, the study found. The most common adverse effects of the drug included diarrhea (24%), nausea (18%) and fatigue (15%). 

These results have put the drug’s development on a fast track,
prompting the accelerated initiation of a large phase III trial.