Preliminary results of an open labelled phase 2 study evaluating the safety and efficacy of sorafenib in metastatic advanced thyroid cancer
Masood Ahmed, Yolanda Barbáchano, Angela M. Riddell, Sadie Whittaker, Kate L. Newbold, Kevin Joseph Harrington, Richard Marais, C. M. Nutting · Journal of Clinical Oncology · 2008
6060 Background: Sorafenib exerts both anti-tumour and anti-angiogenic effects from tyrosine kinase inhibition (TKI) of BRAF, VEGF, c-kit and RET. This study is designed to assess the activity and safety profile of sorafenib in advanced/metastatic thyroid cancer patients. Methods: Patients with advanced/metastatic medullary (med) or differentiated (diff) thyroid cancer and age >18, PS 0 -1, iodine refractory measurable disease, no prior treatment with TKI, adequate hepatic, renal and haematological function are eligible. The study is IRB/REC and MHRA approved (Eudract 2006–006615–80). Primary end point is best objective overall response (BOR) following 6 months of study drug as determined by modified RECIST criteria incorporating radiological (CT) and biochemical (tumour marker) responses. Secondary end points include BOR at 3, 9 and 12 months, safety and tolerability, biomarkers, and progression free survival. Results: Since May 2007, 18 (10 Med, 8 Diff) patients recruited to the study have commenced the drug. 10 patients have follow up at 3 months and 2 of these patients have follow up at 6 months. The remainder have been on the drug for < 3 months and can not yet be assessed. At 3 months BOR for 9 patients is stable disease (SD) and one patient has demonstrated a partial response (PR). At 6 months 2/2 pts have SD. Biochemically 7 out of 7 assessable patients have demonstrated a PR. Common adverse events (AEs) include diarrhoea (G1/2=50%), hand foot syndrome (G1/2=39%, G3=17%), other skin toxicity (G1/2=44%, G3=6%), alopecia (G1/2=28%), hypertension (G1/2=22%, G3=6%), infection (G1/2=17%, G3=6%) and nausea (G1/2=17%). Three drug related SAEs have been reported (two hospitalisations for non-neutropenic fever associated with infection and one for prolonged hypocalcaemia). 78% of patients have required a dose reduction from the starting dose of 400 mg b.d. Conclusions: Sorafenib appears tolerable and early results suggest promising efficacy in advanced medullary and differentiated thyroid cancers despite dose reductions. No significant financial relationships to disclose.