Bevacizumab monotherapy as salvage therapy for patients with advanced clear cell renal cell carcinoma pretreated with targeted drugs.

Abstract

468 Background: Bevacizumab targets vascular endothelial growth factor (VEGF) and has showed benefit in first-line treatment of metastatic clear cell renal cell carcinoma (ccRCC) in combination with interferon α (Lancet 370: 2103). This retrospective analysis assessed the efficacy of bevacizumab monotherapy after progression on targeted drugs such as VEGFr tyrosine kinase inhibitors (TKI), and/or mTOR inhibitors. Methods: A retrospective analysis was performed on patients with metastatic ccRCC who received bevacizumab monotherapy at MSKCC after progression on prior targeted therapies. Primary end point is overall survival and secondary endpoints include progression free survival, time on therapy, and toxicity analysis. Results: 71 patients were treated with bevacizumab monotherapy in the salvage setting. Patients were heavily pretreated with 36 (51%) patients receiving bevacizumab as a fourth-line agent or later and 33 (46%) patients received at least 2 prior VEGF targeted agents. Seventeen (24%) patients had a KPS <80% and 20 (28%) patients were in the poor prognosis MSKCC risk group. Overall median OS was 11.5 months (95% CI, 6.4-17.4 months) and overall median PFS was 1.9 months (95% CI, 1.7-4.1). Nine (13%) patients had a prolonged time on therapy of >12 months. At last analysis, 8 (11%) patients remained on therapy. Therapy was discontinued for progression of disease (n=56, 89%), adverse events (n=4, 6%), or unknown/unrelated reasons (n=3, 5%). Univariate analysis showed KPS (<80% vs. ≥80%) and MSKCC Risk Factor Classification (poor vs. favorable) as prognostic for poor outcome with hazard ratios of 3.97 (95% CI, 2.09-7.52, p<0.001) and 2.84 (95% CI, 1.17-6.89, p=0.021), respectively. No significant differences in OS were seen when comparing number of lines of prior therapy or lines of prior VEGF targeted therapy. Conclusions: Bevacizumab monotherapy resulted in prolonged disease control in a subset of patients with few discontinuations for adverse events in patients after progression on other targeted therapies, including those who were heavily pretreated. The number of prior VEGF targeted TKI therapies did not correlate with response to bevacizumab, which may reflect a difference in targeting the receptor vs. ligand.