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

Epidermal growth factor receptor expression in renal cell carcinoma: Rationale for therapy with sidling blockade

“…In a recent report Hainsworth et al [12] noted that the combination of bevacizumab and erlotinib produced a regression rate of over 20% in patients with metastatic renal cell carcinoma, supporting the suggestion that there may be interactions. This study is being replicated in a randomized placebo controlled phase II trial in untreated patients with metastatic clear cell cancer.…”

Novel kinase inhibitors in renal cell carcinoma: Progressive development of static agents

“…The data reported by Hainsworth et al [39] also raise questions about the best potential approaches of conducting combination studies of cytostatic agents (with each other as well as cytotoxic agents). Given the paucity of available resources, one approach should be to at least pursue modestly sized randomized phase II study designs in an attempt to identify combinations that should be moved forward into phase III studies.…”

“…However, both studies with EGFR inhibitors were small single-arm phase II trials; hence, both trials as designed could have missed clinically relevant benefit. The loss of pVHL function can increase transforming growth factor (TGF)-α (the ligand for EGFR) and VEGF production; hence, Hainsworth et al [39] hypothesized that combining an EGFR and a VEGF inhibitor might lead to superior outcomes. They conducted a phase II trial of erlotinib, administered orally at 150 mg/d, in combination with bevacizumab, administered at 10 mg/kg every 2 weeks.…”

Angiogenesis and angiogenic inhibitors in renal cell carcinoma

“…This is based on preclinical data from human RCC xenograft models in which this combination has demonstrated tumor growth inhibition [47]. A phase II clinical trial in metastatic RCC with bevacizumab (10 mg/kg intravenously every 2 weeks) in combination with erlotinib (150 mg/d orally) reported a 25% partial response rate [48]. Another multicenter, randomized, double-blind, phase II trial showed an overall response rate of 14% for this combination and no statistical difference in PFS [49•].…”