A phase II study of lapatinib and bevacizumab as treatment for HER2-overexpressing metastatic breast cancer Journal Article


Authors: Rugo, H. S.; Jo Chien, A.; Franco, S. X.; Stopeck, A. T.; Glencer, A.; Lahiri, S.; Arbushites, M. C.; Scott, J.; Park, J. W.; Hudis, C.; Nulsen, B.; Dickler, M. N.
Article Title: A phase II study of lapatinib and bevacizumab as treatment for HER2-overexpressing metastatic breast cancer
Abstract: Preclinical data have demonstrated that the combination of antihuman epidermal growth factor receptor-2 (anti-HER2) and antivascular endothelial growth factor (anti-VEGF)-targeted agents has antitumor activity; these data indicate certain patients with HER2-overexpressing breast cancer may derive clinical benefit from this combination. The purpose of this single-arm phase II study was to determine the efficacy and safety of the dual-targeting combination of lapatinib and bevacizumab. Women with HER2-overexpressing advanced breast cancer received 1,500 mg oral lapatinib daily plus 10 mg/kg IV bevacizumab every 2 weeks. The primary endpoint was progression-free survival (PFS) at week 12; secondary endpoints included overall tumor response rate (ORR), clinical benefit rate (CBR), duration of response, time-to-response, PFS, and safety. Circulating tumor cells (CTC) and circulating endothelial cells (CEC) were measured at baseline and during study treatment as potential response markers. Fifty-two patients with stage IV disease were enrolled. The 12-week investigator-assessed PFS rate was 69.2% (95% confidence interval [CI]: 54.9, 81.3). Median PFS was 24.7 weeks (95% CI: 20.4, 35.1), and the CBR was 30.8% (95% CI: 18.7, 45.1). Of 45 patients with measurable disease, 6 were determined to have a partial response per Response Evaluation Criteria in Solid Tumors (ORR: 13.3%; 95% CI: 5.1, 26.8). The most common adverse events (AEs) included diarrhea, rash, and fatigue; most of these were either grade 1 or 2. Clinical responses were correlated with decreases in CTC and CEC. Lapatinib plus bevacizumab was active in patients with HER2-overexpressing breast cancer. The AE profile of the combination was consistent with the known profiles for these agents. © 2011 The Author(s).
Keywords: adult; controlled study; treatment outcome; aged; disease-free survival; middle aged; major clinical study; fatigue; review; bevacizumab; diarrhea; drug dose reduction; drug efficacy; drug safety; drug withdrawal; gastrointestinal hemorrhage; heart left ventricle failure; hypertension; side effect; disease marker; anorexia; gene overexpression; progression free survival; drug eruption; phase 2 clinical trial; breast cancer; gene expression; anemia; nausea; antineoplastic combined chemotherapy protocols; proportional hazards models; epidermal growth factor receptor 2; breast neoplasms; endothelium cell; correlation analysis; multicenter study; cancer cell; drug response; neoplasm metastasis; targeted therapy; receptor, erbb-2; hyperbilirubinemia; headache; tyrosine kinase inhibitor; quinazolines; epistaxis; lapatinib; her2; hydronephrosis; vegf; gastritis; antibodies, monoclonal, humanized; clinical benefit rate; duration of response; time to response
Journal Title: Breast Cancer Research and Treatment
Volume: 134
Issue: 1
ISSN: 0167-6806
Publisher: Springer  
Date Published: 2012-07-01
Start Page: 13
End Page: 20
Language: English
DOI: 10.1007/s10549-011-1918-z
PROVIDER: scopus
PMCID: PMC3397213
PUBMED: 22198412
DOI/URL:
Notes: --- - "Export Date: 1 August 2012" - "CODEN: BCTRD" - "Source: Scopus"
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MSK Authors
  1. Clifford Hudis
    900 Hudis
  2. Maura N Dickler
    261 Dickler
  3. Benjamin Francis Nulsen
    8 Nulsen