Trastuzumab emtansine: A unique antibody-drug conjugate in development for human epidermal growth factor receptor 2-positive cancer
Clinical Cancer Research, ISSN: 1078-0432, Vol: 17, Issue: 20, Page: 6437-6447
2011
- 404Citations
- 384Captures
- 5Mentions
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Metrics Details
- Citations404
- Citation Indexes400
- 400
- CrossRef365
- Patent Family Citations3
- Patent Families3
- Policy Citations1
- Policy Citation1
- Captures384
- Readers384
- 384
- Mentions5
- References4
- Wikipedia4
- News Mentions1
- News1
Most Recent News
Paving the Way for Better Outcomes in HER2+ Early Breast Cancer Treatment
Optimizing treatment for early-stage human epidermal growth receptor 2 (HER2)-positive (HER2+) breast cancer (BC) requires a nuanced approach, integrating targeted therapies and personalized strategies to
Review Description
Trastuzumab emtansine (T-DM1) is a human epidermal growth factor receptor (HER2)-targeted antibodydrug conjugate, composed of trastuzumab, a stable thioether linker, and the potent cytotoxic agent DM1 (derivative of maytansine), in phase III development for HER2-positive cancer. Extensive analysis of T-DM1 in preclinical studies has shown that T-DM1 combines the distinct mechanisms of action of both DM1 and trastuzumab, and has antitumor activity in trastuzumab- and lapatinib-refractory experimental models. Clinically, T-DM1 has a consistent pharmacokinetics profile and minimal systemic exposure to free DM1, with no evidence of DM1 accumulation following repeated T-DM1 doses. Although a few covariates were shown to affect interindividual variability in T-DM1 exposure and clearance in population-pharmacokinetics analyses, the magnitude of their effect on T-DM1 exposure was not clinically relevant. Phase I and phase II clinical trials of T-DM1 as a single agent and in combination with paclitaxel, docetaxel, and pertuzumab have shown clinical activity and a favorable safety profile in patients with HER2-positive metastatic breast cancer. Two randomized phase III trials of T-DM1 are recruiting patients: EMILIA (NCT00829166) is evaluating T-DM1 compared with lapatinib plus capecitabine, andMARIANNE(NCT01120184) is evaluating T-DM1 plus placebo versus T-DM1 plus pertuzumab versus trastuzumab plus a taxane. Additional combinations of T-DM1 (for example, with GDC-0941) and additional disease settings (early-stage HER2-positive breast cancer) are also under investigation. Data from the phase III trials and other studies of T-DM1-containing agents are eagerly awaited. ©2011 AACR.
Bibliographic Details
http://www.scopus.com/inward/record.url?partnerID=HzOxMe3b&scp=80054092983&origin=inward; http://dx.doi.org/10.1158/1078-0432.ccr-11-0762; http://www.ncbi.nlm.nih.gov/pubmed/22003071; https://aacrjournals.org/clincancerres/article/17/20/6437/76533/Trastuzumab-Emtansine-A-Unique-Antibody-Drug; http://clincancerres.aacrjournals.org/cgi/doi/10.1158/1078-0432.CCR-11-0762; https://syndication.highwire.org/content/doi/10.1158/1078-0432.CCR-11-0762; https://dx.doi.org/10.1158/1078-0432.ccr-11-0762; https://clincancerres.aacrjournals.org/content/17/20/6437
American Association for Cancer Research (AACR)
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