Bevacizumab Monotherapy as Salvage Therapy for Advanced Clear Cell Renal Cell Carcinoma Pretreated With Targeted Drugs

Abstract

Bevacizumab has shown benefit in the first-line setting in combination with interferon; however, data on use as monotherapy are limited. In this retrospective analysis of 71 patients we assessed the efficacy of bevacizumab monotherapy in patients whose disease progressed during treatment with other targeted drugs. Bevacizumab monotherapy resulted in prolonged disease control and few discontinuations for adverse events, including for patients who were heavily pretreated.

Background: Bevacizumab has shown benefit in the first-line treatment of metastatic clear cell renal cell carcinoma (ccRCC) in combination with interferon α. In this retrospective analysis we assessed the efficacy of bevacizumab monotherapy in patients whose disease progressed during treatment with vascular endothelial growth factor (VEGF) receptor tyrosine kinase inhibitors, and/or mammalian target of rapamycin inhibitors.

Patients and methods: A retrospective analysis was performed on metastatic ccRCC patients who received bevacizumab monotherapy after their disease progressed during treatment with previous targeted therapies. The primary objective was to assess overall survival (OS) and the secondary objectives includes progression-free survival (PFS), therapy duration, and incidence of serious adverse events assessed during visits to the Memorial Sloan Kettering Cancer Center (MSKCC) urgent care center.

Results: Seventy-one patients were treated with bevacizumab as monotherapy in the salvage setting. Most patients were heavily pretreated with 36 patients (51%) who received bevacizumab as a fourth-line or later agent, and 33 patients (46%) who received at least 2 previous VEGF targeted agents. Eighteen patients (25%) had a Karnofsky Performance Status (KPS) < 80%, and 20 patients (28%) were classified as poor risk according to MSKCC criteria. Median OS was 11.5 months (95% confidence interval [CI], 6.4-17.4), and median PFS was 1.9 months (95% CI, 1.7-4.1). Nine patients (13%) had a prolonged time of therapy of > 12 months. Four patients (6%) discontinued therapy because of adverse events. Poor KPS (< 80%) and MSKCC poor-risk classification were prognostic for poor OS with hazard ratios of 4.09 (P < .001) and 2.84 (P = .021), respectively.

Conclusion: Bevacizumab monotherapy resulted in prolonged disease control and few discontinuations because of adverse events in patients whose disease had progressed during treatment with other targeted therapies, including patients who were heavily pretreated.

Keywords: Kidney cancer; Retrospective analysis; TKI; VEGF; mTOR.