Faculty Collaboration Database

Dual HER2 inhibition in combination with anti-VEGF treatment is active in heavily pretreated HER2-positive breast cancer. Ann Oncol 2013 Dec;24(12):3004-11

Date

10/26/2013

Pubmed ID

24158411

Pubmed Central ID

PMC3841018

DOI

10.1093/annonc/mdt395

Scopus ID

2-s2.0-84888816383 (requires institutional sign-in at Scopus site)   26 Citations

Abstract

BACKGROUND: Preclinical data indicate that dual HER2 inhibition overcomes trastuzumab resistance and that use of an HER2 inhibitor with an anti-angiogenic agent may augment responses.

PATIENTS AND METHODS: We conducted a dose-escalation, phase I study of a combination of trastuzumab, lapatinib and bevacizumab. The subset of patients with metastatic breast cancer was analyzed for safety and response.

RESULTS: Twenty-six patients with metastatic breast cancer (median = 7 prior systemic therapies) (all with prior trastuzumab; 23 with prior lapatinib; one with prior bevacizumab) received treatment on a range of dose levels. The most common treatment-related grade 2 or higher toxicities were diarrhea (n = 11, 42%) and skin rash (n = 2, 8%). The recommended phase 2 dose was determined to be the full Food and Drug Administration (FDA) approved doses for all the three agents (trastuzumab 8 mg/kg loading dose, 6 mg/kg maintenance dose, intravenously every 3 weeks; lapatinib 1250 mg daily, bevacizumab 15 mg/kg intravenously every 3 weeks). The overall rate of stable disease (SD) ≥6 months and partial or complete remission (PR/CR) was 50% (five patients with SD ≥6 months; seven PRs (including one unconfirmed); one CR). The rate of SD ≥6 months/PR/CR was not compromised in patients who had previously received study drugs, those with brain metastases, and patients treated at lower dose levels.

CONCLUSIONS: The combination of trastuzumab, lapatinib and bevacizumab was well-tolerated at maximally approved doses of each drug, and its activity in heavily pretreated patients with metastatic breast cancer suggests that it warrants further investigation.

CLINTRIALSGOV ID: NCT00543504.

Author List

Falchook GS, Moulder SL, Wheler JJ, Jiang Y, Bastida CC, Kurzrock R

Author

Razelle Kurzrock MD Center Associate Director, Professor in the Medicine department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Adult
Aged
Antibodies, Monoclonal, Humanized
Antineoplastic Combined Chemotherapy Protocols
Bevacizumab
Brain Neoplasms
Breast Neoplasms
Carcinoma, Ductal, Breast
Dose-Response Relationship, Drug
Drug Administration Schedule
Drug Resistance, Neoplasm
Female
Humans
Maximum Tolerated Dose
Middle Aged
Quinazolines
Receptor, ErbB-2
Receptors, Vascular Endothelial Growth Factor
Trastuzumab
Treatment Outcome