Phase II trial of bevacizumab and erlotinib in patients with metastatic renal carcinoma (RCC)

Abstract

4502 Background: Treatment for advanced RCC remains poor, with meaningful responses in a small minority. Most pts with clear cell RCC have loss of VHL protein primarily due to gene mutation, resulting in impaired breakdown of HIF-1proportion and overexpression of HIF-1proportion regulated genes including VEGF, TGF-proportion, EGF, and PDGF. Bevacizumab (Avastin), an anti-VEGF antibody prolongs TTP in second-line therapy of advanced RCC versus placebo. Based on RCC biology, we hypothesized that combined VEGF and EGFR inhibition would enhance biological and clinical effects. Methods: In this phase II trial, we administered bevacizumab with erlotinib (Tarceva), an EGFR antagonist. Eligible pts had metastatic clear cell RCC, and 0 or 1 previous systemic regimens. Additional eligibility criteria: previous nephrectomy (if clinically appropriate); no previous anti-angiogenesis agents or EGFR inhibitors; ECOG PS 0 or 1; adequate organ function; no active CNS metastases; no bleeding abnormalities; no history of thromboembolic disease. All pts received bevacizumab 10mg/kg IV q 2 weeks, and erlotinib 150mg PO daily. Pts were evaluated for response after 8 weeks; treatment continued until tumor progression. Results: Between 2/03 and 11/03, 57 pts were treated: median age 60 years; male/female, 45/12; previous nephrectomy, 53; sites of metastases: lungs 41, liver 17, bone 15, adrenals 10, other 14; previous treatment: none 34, IL2 and/or IFN 18. 40 pts have been evaluated after 8 weeks of therapy. Current response rates: partial response, 10 pts (25%; 95% CI 13%–41%); minor response (20–30% decrease), 6 pts (15%); stable, 19 pts (47%); progression, 5 pts (12%). 27 pts continue treatment after median follow-up of 4.4 months. Actuarial PFS at 6 months is 71%. Treatment was well tolerated; 25 pts (63%) had no grade 3/4 toxicity. Grade 3/4 toxicity: hypertension 11%; diarrhea 9%; rash 7%; nausea/vomiting 7%; pruritus 4%; edema 2%. Conclusions: Bevacizumab/erlotinib treatment has substantial clinical activity in pts with metastatic RCC. The combination seems more active than either agent alone, and supports the concept of combined inhibition of critical pathways. Updated results on 60 pts will be presented. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Genentech Genentech