Bevacizumab with or without erlotinib in metastatic renal cell carcinoma (RCC)

Abstract

4523 Background: Bevacizumab (B) has clinical efficacy in metastatic RCC following cytokine treatment. A single-arm Phase II trial suggested potential clinical benefit of adding erlotinib (E) to B. To further assess this combination in RCC, we conducted a multicenter, randomized, double-blind Phase 2 trial comparing B+E vs B + placebo. Methods: Eligibility criteria included: previously untreated metastatic RCC with >50% clear cell histology; previous nephrectomy; ECOG PS 0 or 1; measurable disease; serum Ca++ ≤ 10 mg/dL; LDH ≤ 1.5 ULN; Hgb ≥ 9 g/dL; and standard exclusion criteria for B. All pts received B 10 mg/kg IV q 2 wk with either E 150 mg po daily or placebo until disease progression or unacceptable toxicity. Tumors were assessed using RECIST every 8 wks. A landmark analysis was performed 9 mo after accrual of the last pt. Objective response rate (ORR) and progression-free survival (PFS) were co-primary endpoints. Secondary endpoints included response duration, overall survival, and safety. Results: 104 pts (53 B, 51 B+E) were enrolled at 20 sites from Mar 2004–Oct 2004. 65 pts have discontinued therapy. 55 have progressed (PFS HR = 0.86, CI 0.5, 1.49). Median follow-up was 9.8 mo. Median survival duration was not reached. Only 1 treatment-related death due to GI perforation occurred (on B+E). Updated safety and survival data will be presented. Conclusions: B+E and B were well tolerated. Adding E does not appear to improve efficacy from B. PFS of 8.5 months with B compares favorably with the historical PFS of ∼ 4.7 mo with interferon alpha (IFN). Results of phase III trials comparing IFN ± B are pending. [Table: see text] [Table: see text]