A phase II study of trastuzumab emtansine in patients with human epidermal growth factor receptor 2-positive metastatic breast cancer who were previously treated with trastuzumab, lapatinib, an anthracycline, a taxane, and capecitabine Journal Article


Authors: Krop, I. E.; LoRusso, P.; Miller, K. D.; Modi, S.; Yardley, D.; Rodriguez, G.; Guardino, E.; Lu, M.; Zheng, M.; Girish, S.; Amler, L.; Winer, E. P.; Rugo, H. S.
Article Title: A phase II study of trastuzumab emtansine in patients with human epidermal growth factor receptor 2-positive metastatic breast cancer who were previously treated with trastuzumab, lapatinib, an anthracycline, a taxane, and capecitabine
Abstract: Purpose: To determine whether the antibody-drug conjugate trastuzumab emtansine (T-DM1), which combines human epidermal growth factor receptor 2 (HER2) -targeted delivery of the potent antimicrotubule agent DM1 with the antitumor activity of trastuzumab, is effective in patients with HER2-positive metastatic breast cancer (MBC) who have previously received all standard HER2-directed therapies. Patients and Methods: In this single-arm phase II study, T-DM1 3.6 mg/kg was administered intravenously every 3 weeks to patients with HER2-positive MBC who had prior treatment with trastuzumab, lapatinib, an anthracycline, a taxane, and capecitabine. The primary objectives were overall response rate (ORR) by independent review and safety. Results: Among 110 pretreated patients (median, seven prior agents for MBC; median follow-up, 17.4 months), the ORR was 34.5% (95% CI, 26.1% to 43.9%), clinical benefit rate was 48.2% (95% CI, 38.8% to 57.9%), median progression-free survival (PFS) was 6.9 months (95% CI, 4.2 to 8.4 months), and median duration of response was 7.2 months (95% CI, 4.6 months to not estimable). In patients with confirmed HER2-positive tumors (n = 80 by retrospective central testing), the response rate was 41.3% (95% CI, 30.4% to 52.8%), and median PFS was 7.3 months (95% CI, 4.6 to 12.3 months). Most adverse events were grades 1 to 2; the most frequent grade ≥ 3 events were thrombocytopenia (9.1%), fatigue (4.5%), and cellulitis (3.6%). Conclusion: T-DM1 is well tolerated and has single-agent activity in patients with HER2-positive MBC who have previously received both approved HER2-directed therapies and multiple chemotherapy agents. T-DM1 may be an effective new treatment for this patient population. © 2012 by American Society of Clinical Oncology.
Keywords: adult; protein expression; treatment response; aged; disease-free survival; middle aged; major clinical study; constipation; fatigue; fluorouracil; diarrhea; drug efficacy; drug safety; drug withdrawal; side effect; antineoplastic agents; capecitabine; follow up; progression free survival; liver toxicity; phase 2 clinical trial; anemia; basal cell carcinoma; nausea; thrombocytopenia; vomiting; myalgia; peripheral neuropathy; epidermal growth factor receptor 2; body weight; antineoplastic activity; breast neoplasms; phosphatidylinositol 3 kinase; abdominal pain; arthralgia; backache; coughing; dyspnea; fever; hyperglycemia; pneumonia; hypokalemia; depression; cardiotoxicity; spinal cord compression; neoplasm metastasis; xerostomia; limb pain; sepsis; receptor, erbb-2; taxoids; headache; maximum plasma concentration; liver function test; taxane derivative; drug half life; trastuzumab; anthracycline; breast metastasis; heart left ventricle ejection fraction; muscle spasm; anthracyclines; deoxycytidine; quinazolines; epistaxis; congestive heart failure; lapatinib; ixabepilone; maytansine; cellulitis; decreased appetite; bridged compounds; immunotoxins; molecular targeted therapy; trastuzumab emtansine; antibodies, monoclonal, humanized; infusion related reaction
Journal Title: Journal of Clinical Oncology
Volume: 30
Issue: 26
ISSN: 0732-183X
Publisher: American Society of Clinical Oncology  
Date Published: 2012-09-10
Start Page: 3234
End Page: 3241
Language: English
DOI: 10.1200/jco.2011.40.5902
PUBMED: 22649126
PROVIDER: scopus
DOI/URL:
Notes: --- - "Cited By (since 1996): 9" - "Export Date: 28 January 2013" - "CODEN: JCOND" - "Source: Scopus"
Altmetric
Citation Impact
MSK Authors
  1. Shanu Modi
    171 Modi