A phase 1 study of weekly dosing of trastuzumab emtansine (T-DM1) in patients with advanced human epidermal growth factor 2-positive breast cancer Journal Article
| Authors: | Beeram, M.; Krop, I. E.; Burris, H. A.; Girish, S. R.; Yu, W.; Lu, M. W.; Holden, S. N.; Modi, S. |
| Article Title: | A phase 1 study of weekly dosing of trastuzumab emtansine (T-DM1) in patients with advanced human epidermal growth factor 2-positive breast cancer |
| Abstract: | BACKGROUND: We conducted a phase 1, multicenter, open-label, dose-escalation study (TDM3569g) to assess the safety, tolerability, and pharmacokinetics of single-agent trastuzumab emtansine (T-DM1) administered weekly and once every 3 weeks in patients with HER2-positive metastatic breast cancer previously treated with trastuzumab. The weekly dose results are described here. METHODS: Patients were administered escalating doses of T-DM1 weekly, starting at 1.2 mg/kg. Additional patients were enrolled at the maximum tolerated dose (MTD) to better characterize tolerability and pharmacokinetics. RESULTS: Twenty-eight patients received weekly T-DM1, and the MTD was determined to be 2.4 mg/kg. In general, T-DM1 was well tolerated, requiring few dose modifications or discontinuations because of adverse events (AEs). Grade ≥3 AEs were reported in 19 patients (67.9%); treatment-related AEs occurred in 25 (89.3%) patients. Exposure to weekly T-DM1 was dose-proportional at ≥1.2 mg/kg, and accumulation of T-DM1 and total trastuzumab was observed. Objective partial tumor responses were reported in 13 (46.4%) patients; the median duration of response was 18.6 months, and the 6-month clinical benefit rate was 57.1%. CONCLUSION: The results suggest that a weekly dose of T-DM1 2.4 mg/kg has antitumor activity and is well tolerated in patients with HER2-positive metastatic breast cancer. © 2012 American Cancer Society. |
| Keywords: | epidermal growth factor; adult; controlled study; treatment response; aged; middle aged; unclassified drug; constipation; drug tolerability; fatigue; neutropenia; area under the curve; diarrhea; drug safety; drug withdrawal; hepatic encephalopathy; side effect; treatment duration; antineoplastic agents; liver dysfunction; anorexia; neutrophil count; pain; sensory neuropathy; breast cancer; anemia; steady state; bleeding; leukopenia; lung disease; nausea; thrombocytopenia; vomiting; peripheral neuropathy; calcium blood level; antineoplastic activity; breast neoplasms; arthralgia; chill; drug dose escalation; drug fever; dyspnea; pneumonia; lung embolism; confusion; drug induced headache; gastrointestinal toxicity; drug distribution; multicenter study; immunogenicity; xerostomia; drug clearance; glucose blood level; open study; receptor, erbb-2; alkaline phosphatase blood level; maximum plasma concentration; metastasis potential; eye disease; liver function test; maximum tolerated dose; phase 1 clinical trial; drug half life; dry eye; sodium blood level; influenza; epistaxis; uric acid blood level; maytansine; dysgeusia; cellulitis; osteomyelitis; immunotoxins; her2-positive; trastuzumab emtansine; potassium blood level; antibodies, monoclonal, humanized; antibody-drug conjugate; t-dm1; epidermal growth factor 2 |
| Journal Title: | Cancer |
| Volume: | 118 |
| Issue: | 23 |
| ISSN: | 0008-543X |
| Publisher: | Wiley Blackwell |
| Date Published: | 2012-12-01 |
| Start Page: | 5733 |
| End Page: | 5740 |
| Language: | English |
| DOI: | 10.1002/cncr.27622 |
| PROVIDER: | scopus |
| PUBMED: | 22648179 |
| DOI/URL: | |
| Notes: | --- - "Export Date: 3 December 2012" - "CODEN: CANCA" - "Source: Scopus" |
