This Article Full Text Full Text (PDF) Supplementary Data Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Dickler, M. N. Articles by Hudis, C. A. Search for Related Content PubMed PubMed Citation Articles by Dickler, M. N. Articles by Hudis, C. A.

A Phase II Trial of Erlotinib in Combination with Bevacizumab in Patients with Metastatic Breast Cancer

Authors' Affiliations: ¹ Breast Cancer Medicine Service and ² Departments of Pathology, ³ Radiology, and ⁴ Biostatistics, Memorial Sloan-Kettering Cancer Center, New York, New York; ⁵ University of California San Francisco Comprehensive Cancer Center San Francisco, California, ⁶ Memorial Health University Medical Center, Savannah, Georgia; and ⁷ National Cancer Institute Bethesda, Maryland

Requests for reprints: Maura N. Dickler, Breast Cancer Medicine Service, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, New York, NY 10021. Phone: 646-888-4560; Fax: 646-888-4555; E-mail: dicklerm{at}mskcc.org.

Purpose: To evaluate the efficacy and toxicity of erlotinib plus bevacizumab in patients with metastatic breast cancer (MBC), targeting the epidermal growth factor receptor (EGFR/HER1) and the vascular endothelial growth factor (VEGF) pathway.

Experimental Design: Thirty-eight patients with MBC were enrolled and treated at two institutions with erlotinib, a small molecule EGFR tyrosine kinase inhibitor (150 mg p.o. daily) plus bevacizumab, an anti-VEGF antibody (15 mg/kg i.v. every 3 weeks). Patients had one to two prior chemotherapy regimens for metastatic disease. The primary end point was response rate by Response Evaluation Criteria in Solid Tumors criteria using a Simon 2-stage design. Secondary end points included toxicity, time to progression, response duration, and stabilization of disease of 26 weeks. Correlative studies were done on tumor tissue, including EGFR expression and mutation analysis.

Results: One patient achieved a partial response for 52+ months. Fifteen patients had stable disease at first evaluation at 9 weeks; 4 of these patients had stable disease beyond 26 weeks. Median time to progression was 11 weeks (95% confidence interval, 8-18 weeks). Diarrhea of any grade was observed in 84% of patients (grade 3 in 3%); 76% experienced grade 1 or 2 skin rash, and 18% developed hypertension (grade 3 in 11%). The level of EGFR expression was not predictive of response to therapy.

Conclusions: The combination of erlotinib and bevacizumab was well-tolerated but had limited activity in unselected patients with previously treated MBC. Biomarkers are needed to identify those MBC patients likely to respond to anti-EGFR/HER1 plus anti-VEGF therapy.

This article has been cited by other articles:

				A. Jimeno Eribulin: Rediscovering Tubulin as an Anticancer Target Clin. Cancer Res., June 15, 2009; 15(12): 3903 - 3905. [Abstract] [Full Text] [PDF]