A phase II trial of erlotinib in combination with bevacizumab in patients with metastatic breast cancer Journal Article
| Authors: | Dickler, M. N.; Rugo, H. S.; Eberle, C.; Brogi, E.; Caravelli, J.; Panageas, K. S.; Boyd, J.; Yeh, B.; Lake, D. E.; Dang, C.; Gilewski, T. A.; Bromberg, J. F.; Seidman, A. D.; D'Andrea, G.; Moasser, M. M.; Melisko, M.; Park, J. W.; Dancey, J.; Norton, L.; Hudis, C. A. |
| Article Title: | A phase II trial of erlotinib in combination with bevacizumab in patients with metastatic breast cancer |
| Abstract: | Purpose: To evaluate the efficacy and toxicity of erlotinib plusbevacizumab 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 patientswith 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 regimensfor metastatic disease. The primary end point wasresponse 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 waswell-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. © 2008 American Association for Cancer Research. |
| Keywords: | immunohistochemistry; vasculotropin; adult; clinical article; controlled study; protein expression; treatment outcome; treatment response; aged; middle aged; clinical trial; drug tolerability; fatigue; bevacizumab; doxorubicin; erlotinib; cancer combination chemotherapy; cancer growth; diarrhea; drug dose reduction; drug efficacy; drug withdrawal; hypertension; paclitaxel; adjuvant therapy; antineoplastic agent; biological marker; metastasis; controlled clinical trial; multiple cycle treatment; phase 2 clinical trial; breast cancer; stomatitis; vomiting; antineoplastic combined chemotherapy protocols; dehydration; myalgia; epidermal growth factor receptor; cyclophosphamide; pathology; mutational analysis; breast neoplasms; docetaxel; monoclonal antibody; arthralgia; lymphocytopenia; pruritus; rash; antibodies, monoclonal; multicenter study; thrombosis; breast tumor; acne; gefitinib; loperamide; taxane derivative; toxicity; trastuzumab; anthracycline; dyspepsia; dry eye; dry skin; quinazolines; tetracycline; epistaxis; vasculotropin antibody; proteinuria; quinazoline derivative; epidermal growth factor receptor antibody; skin allergy; low back pain |
| Journal Title: | Clinical Cancer Research |
| Volume: | 14 |
| Issue: | 23 |
| ISSN: | 1078-0432 |
| Publisher: | American Association for Cancer Research |
| Date Published: | 2008-12-01 |
| Start Page: | 7878 |
| End Page: | 7883 |
| Language: | English |
| DOI: | 10.1158/1078-0432.ccr-08-0141 |
| PUBMED: | 19047117 |
| PROVIDER: | scopus |
| PMCID: | PMC2748748 |
| DOI/URL: | |
| Notes: | --- - "Cited By (since 1996): 24" - "Export Date: 17 November 2011" - "CODEN: CCREF" - "Source: Scopus" |
