Presurgical bevacizumab in patients with metastatic clear cell renal cell carcinoma: A phase II study.

5104 Background: The increasing use of targeted therapies in metastatic renal cell carcinoma (mRCC) has raised questions about the timing of cytoreductive nephrectomy. We initiated a phase II trial to evaluate the safety and efficacy of presurgical bevacizumab (bev) in newly diagnosed patients (pts) with mRCC, with the hope of improving clinical outcomes and to obtain tissue for correlative studies.,Pts with conventional-type mRCC with PS 0/1, resectable primary tumor and no brain metastasis received bev 10 mg/kg iv q2wks (plus erlotinib 150 mg daily for the first 25 pts) for 8 wks, followed 4 weeks later by cytoreductive nephrectomy. Primary endpoints: progression free survival (PFS) and safety. Secondary endpoints: response rate (RR), overall survival (OS) and correlative studies. Responding or stable pts resumed bev 4 weeks postoperatively. Response was defined by RECIST. PFS was measured from registration to date of progressive disease (PD) or death from any cause. Overall survival (OS) was measured from registration to date of death from any cause.,Forty-eight of fifty pts have been enrolled. Two pts did not receive study drug and were excluded from the analyses. Median age was 61 (range 35-83). 89% had at least two sites of metastatic disease. 83% had intermediate risk disease, and 17% had poor risk disease. Among the 46 pts who received at least one dose of study drug, 1 achieved a complete response in his target lesion (cCR) but stability in a bone lesion, 4 achieved a partial response (PR), and 27 achieved stable disease (SD). Seven patients did not undergo nephrectomy. Three patients died in the perioperative period. The response rate (cCR + PR) was 10.9% (95% C.l., 3.6-23.6). The clinical benefit rate (cCR + PR + SD) was 69.6% (95% C.I.,54-82.3%). Thirty pts developed PD or died, with median PFS of 6.0 mos (95% C.I,4.9-16.5). Sixteen pts died, with median OS of 25.4 mos (95% C.I.,13.3-Not Estimable). Common adverse events included hypertension, diarrhea, anemia, and abdominal pain. There were no major perioperative complications clearly attributable to study drug.,Presurgical treatment of mRCC patients with bevacizumab is safe and feasible. Clinical outcomes were acceptable considering the relatively high disease burden of the study population. [Table: see text].