Challenges and opportunities for converting renal cell carcinoma into a chronic disease with targeted therapies
4597 Background: Sorafenib and sunitinib are multi-targeted kinase inhibitors (TKI's) with clinical activity in mRCC. Their effect in mRCC pts refractory to prior anti-angiogenic agents is unclear. We investigated the anti-tumor effect of sorafenib and sunitinib in patients with mRCC who failed prior treatment with anti-angiogenic agents. METHODS Pts with mRCC receiving sorafenib and sunitinib on compassionate use trials were identified. Those pts who had received prior treatment with anti-angiogenic agents defined as thalidomide, lenalidomide, M200 (anti-α5β1 integrin monoclonal antibody), bevacizumab, AG013736, sunitinib or sorafenib were selected and their treatment response to current sorafenib or sunitinib evaluated. RESULTS Seventy-two pts (39 receiving sorafenib and 33 receiving sunitinib) were identified. Of these 72 pts, 23 pts (32%) had received prior anti-angiogenic therapy as defined above. Demographics included: 19 male and 4 female, median age 61 years (range 44 to 77). Thirteen pts (57%) are currently evaluable; the remainder are too early for assessment. Twelve pts (92%) demonstrated tumor reduction including 4 pts with objective partial response (PR); 8 pts had stable disease with tumor shrinkage ranging from 4 to 27% and 1 pt had disease progression. Of the 4 PR pts, prior therapy included M200 (1 pt), lenalidomide (2 pts) and sorafenib (1 pt). Of the 13 evaluable pts 4 had failed a prior TKI and received a subsequent TKI and all had evidence of tumor shrinkage to subsequent therapy (sunitinib followed by sorafenib, 1pt - 16% shrinkage, sorafenib followed by sunitinib 2 pts - 33.4% and 24% and AG013736 followed by sunitinib 1 pt - 12% ). CONCLUSION Sorafenib and sunitinib have anti-tumor activity in mRCC pts who have received prior anti-angiogenic agents. [Table: see text].