Phase II trial of erlotinib (OSI-774), an epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitor, and bevacizumab, a recombinant humanized monoclonal antibody to vascular endothelial growth factor (VEGF), in patients (pts) with metastatic breast cancer (MBC)

Abstract

2001 Background: Aberrant VEGFR expression in breast tumor cells and EGFR expression in endothelial cells may contribute to tumor growth and progression (Baker, 2002; Kranz, 1999). Preclinical evidence suggests that EGFR blockade may inhibit angiogenesis (Hirata, 2002), and combined blockade of the VEGFR and EGFR pathways may increase anti-tumor activity in xenograft models (Jung, 2002). We performed this two stage phase II study to explore the activity of erlotinib and bevacizumab in MBC, as a phase I/II trial in lung ca showed no pharmacokinetic interaction (Mininberg, ASCO 2003). Methods: Erlotinib (150 mg orally/day) and bevacizumab (15mg/kg IV q3 weeks) is given to pts with measurable MBC following 1–2 prior chemotherapy regimens (CRx). The primary endpoint is response rate; secondary endpoints include safety and time to tumor progression. Markers of the EGFR and VEGFR pathways will be evaluated in archival tumor tissue and in pre/post treatment tumor biopsies in several pts. Levels of circulating endothelial cells, epithelial cells, VEGF and βFGF will be measured in serial plasma samples. Results: Thirteen pts have been enrolled to date: median age 55 (range 35–71); ECOG 1 (0–2); 75% had 2 prior CRx for MBC. Pts received a total of 38 cycles of study therapy, with median of 2 cycles/pt (range 1–9). Response is evaluable in 9 pts (75%), with 3 pts too early for response assessment. One pt had a confirmed PR (11%), 2 had SD at 9 wks (22%), 5 had POD (56%), and 1 (11%) came off study after 1 cycle due to an allergic drug eruption. Two pts (15%) experienced grade (gr) 4 toxicities: pulmonary embolus 1 (8%) and neutropenia 1 (8%). Toxicity potentially related to OSI-774 and/or bevacizumab include: rash (gr 2: 46%), diarrhea (gr 2: 23%), hypertension (gr 3: 15%), nausea/vomiting (gr 3: 8%). Conclusions: Activity in the first stage of this phase II trial justifies expanded study of erlotinib and bevacizumab in MBC. Updated results with additional pts will be presented. Supported by CTEP, NCI and in part by Genentech Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Genentech Genentech, Inc. Genentech