5529 Background: Elevated levels of VEGF have been found in thyroid tumor tissue compared to normal thyroid. Axitinib (AG-013736) is a novel small molecule inhibitor of the receptor tyrosine kinases with picomolar potency against VEGFR 1, 2 & 3 and nanomolar potency against PDGFR-beta and KIT. A phase I study in solid tumors identified 5 mg BID as the therapeutic dose. A phase II study in renal cell cancer demonstrated significant efficacy with a response rate (RR) of 46% (Rini et al, ASCO 2005). This study examined the safety and efficacy of AG-013736 (AG) therapy for advanced thyroid cancer. Methods: 32 patients (pts) refractory to or not suitable candidates for Iodine (131I) treatment were treated with AG 5 mg p.o. BID. Eligibility included measurable disease and ECOG performance status (PS) of 0 or 1. A Simon 2 stage minimax design was used (alpha = 0.1; beta = 0.1; null response rate (RR) = 5%; alternative RR = 20%). Results: The median age of 32 enrolled pts was 63 yrs (35–81), 20 (63%) were male, 12 (38%) were female. Histological subtypes include papillary: 19 pts (59%); follicular- 9 pts (28%), medullary- 2 pts (6%) and anaplastic-2 pts (6%). 25 pts (78%) had prior surgery, 19 pts (59%) had prior 131I treatment, 15 pts (47%) had prior RT, 6 pts (19%) had prior Adriamycin. Best response as assessed by RECIST criteria is PR in 3 pts with 38%-48% regression and additional unconfirmed PRs in 3 pts. Two pts (follicular) have PR>12 mos. Response assessments are ongoing. 12 patients have discontinued treatment: 6 pts (19%)-progression, 3 pts-adverse events (AEs) and 3 pts-other. Twenty pts (63%) remain on study. The range for time on study is (6, 469) days. Median progression free survival has not been reached. Preliminary safety data for 17 pts indicate most common treatment emergent AEs as fatigue (9 pts), nausea (5 pts), proteinuria ( 5pts ), dizziness (4pts). Gr. 3 AEs include proteinuria ( 2pts ), cough (1pt), dyspnea (1 pt), abdominal pain (1pt), dysphagia (1pt), fatigue (1pt), muscle weakness (1pt), anorexia (1pt). Gr. 2 hypertension was observed in 2 pts. Conclusions: AG-013736 has substantial anti-tumor activity in advanced thyroid cancer. Therapy is well tolerated with manageable toxicity. Further investigation in this setting is warranted. [Table: see text]
Phase Ii Study of Lenvatinib (Len), a Multi-Targeted Tyrosine Kinase Inhibitor, in Patients (Pts) with All Histologic Subtypes of Advanced Thyroid Cancer (Differentiated, Medullary and Anaplastic)