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.
authors.affiliation: Helen Diller Family Comprehensive Cancer Center, University of California San Francisco, 1600 Divisadero St., 2nd Floor, Box 1710, B-608, San Francisco, CA 94143, USA. hrugo@medicine.ucsf.edu
authors.forename: Hope S
authors.initials: HS
authors.lastname: Rugo
authors.forename: A Jo
authors.initials: AJ
authors.lastname: Chien
authors.forename: Sandra X
authors.initials: SX
authors.lastname: Franco
authors.forename: Alison T
authors.initials: AT
authors.lastname: Stopeck
authors.forename: Alexa
authors.initials: A
authors.lastname: Glencer
authors.forename: Soumi
authors.initials: S
authors.lastname: Lahiri
authors.forename: Michael C
authors.initials: MC
authors.lastname: Arbushites
authors.forename: Janet
authors.initials: J
authors.lastname: Scott
authors.forename: John W
authors.initials: JW
authors.lastname: Park
authors.forename: Clifford
authors.initials: C
authors.lastname: Hudis
authors.forename: Ben
authors.initials: B
authors.lastname: Nulsen
authors.forename: Maura N
authors.initials: MN
authors.lastname: Dickler
mesh_terms: D061067:Antibodies, Monoclonal, Humanized / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D000068258:Bevacizumab; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D018572:Disease-Free Survival; D005260:Female; D015870:Gene Expression; D006801:Humans; D000077341:Lapatinib; D008875:Middle Aged; D009362:Neoplasm Metastasis; D016016:Proportional Hazards Models; D011799:Quinazolines / Q000008:administration & dosage; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000235:genetics / Q000378:metabolism*; D016896:Treatment Outcome
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D000068258:Bevacizumab; D000077341:Lapatinib; D011799:Quinazolines; D018719:Erb-b2 Receptor Tyrosine Kinases; C508053:ERBB2 protein, human