Abstract
5503 Background: E7080 is an oral tyrosine kinase inhibitor targeting VEGFR1-3, FGFR1-4, RET, KIT and PDGFRβ. In phase I studies of E7080 partial responses (PR) were observed in thyroid as well as melanoma, endometrial, and renal cancers. Methods: Between Oct 2, 2008 and Feb 5, 2010, patients (pts) with advanced, RAI-refractory DTC (papillary, follicular or Hurthle Cell) and disease progression demonstrated by RECIST during the prior 12 months were enrolled. Pts may have received prior VEGFR targeted therapy. Pts were treated with a starting dose of E7080 24 mg once daily in 28 day cycles until disease progression or development of unmanageable toxicities. Primary end point was Response Rate (RR) by RECIST. Results: 58 pts were enrolled (med age: 62; M:59%, F:41%) and are evaluable for response. 35% of pts required dose reduction for management of toxicity, and 23% were withdrawn from therapy due to toxicity. The most common adverse events were hypertension 64% (Gr 3: 4%), fatigue 55% (Gr3: 7%), diarrhea 45% (Gr3: 5%), decreased appetite 44% (Gr3: 2%), weight loss 43% (Gr3: 4%), and proteinuria 39% (Gr3: 7%). 5 pts (8.6%) experienced Gr 4 events. Confirmed PRs were observed in 29 pts (RR: 50%, 95% CI: 37-63) based on investigator assessment. 65% of responses were identified at first on-therapy imaging at ~8 wks. For pts who received prior VEGFR-directed treatment (n=17) RR=41%; with no prior VEGFR-directed treatment (n=41) RR=54%. Median PFS is 12.6 mo (95% CI: 10.4-14.1) (based on minimum 8 mo. f/u, with only 34% events observed). Updated PFS will be reported. Conclusions: E7080 administered orally at a dose of 24 mg once daily to patients with RAI refractory DTC is associated with manageable toxicity and a RR of 50%, identifying E7080 as a promising new potential therapeutic agent for treating patients affected with this disease which has very limited therapeutic options at present.
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