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A new recruit in the fight against cancer: Why can trastuzumab emtansine change the treatment landscape for HER2-positive breast cancer?
In the fight against cancer, the medical community is constantly seeking innovative technologies and therapies to improve treatment outcomes. Trastuzumab emtansine (trade name Kadcyla), as an antibody drug combination therapy, is gradually changing the treatment landscape for HER2-positive breast cancer. How does this therapy work? Why can it bring about significant improvement in survival compared with traditional treatment?
Trastuzumab emtansine combines the humanized monoclonal antibody trastuzumab with the anticancer drug DM1 to specifically target cancer cells that overexpress the HER2 receptor.
Mechanism of action of trastuzumab emtansine
Trastuzumab alone can inhibit cancer cell proliferation by binding to the HER2 receptor, while trastuzumab emtansine further enters cancer cells through receptor-mediated endocytosis. Once inside the cell, the drug is broken down in lysosomes, releasing DM1, a cytotoxin that inhibits cell division by binding to microtubules, ultimately leading to cell death.
Achievements in Clinical Trials
In the EMILIA clinical trial, women with HER2-positive breast cancer who had not responded to trastuzumab had better outcomes with trastuzumab emtansine than with lapatinib and capecitabine. The combination had a longer survival gain, extending median overall survival by 5.8 months (30.9 months vs. 25.1 months). This achievement is undoubtedly a ray of hope for many cancer patients.The results of the study showed that the median progression-free survival of patients treated with Trastuzumab emtansine reached 9.6 months, significantly better than the 6.4 months in the control group.
Side Effects and Their Management
Although Trastuzumab emtansine showed good efficacy, a series of side effects inevitably occurred in clinical trials. The most common ones include fatigue, nausea, musculoskeletal pain, and thrombocytopenia. In the EMILIA trial, only 43% of patients using trastuzumab emtansine experienced severe toxic reactions, which was relatively good compared with the control group.
Trastuzumab emtansine's boxed warning highlights the risks of liver damage, heart damage, and harm to pregnant women.
Chemical properties
As an antibody-drug combination therapy, the chemical structure of trastuzumab emtansine contains trastuzumab and multiple DM1 molecules. The link creates a chemical bridge between the antibody and the drug, allowing them to precisely deliver the toxin to cancer cells.
Historical BackgroundIn 2013, trastuzumab emtansine was approved in the United States for the treatment of patients with HER2-positive metastatic breast cancer who had previously received trastuzumab and a taxane. The therapy was fast-tracked for approval under the U.S. FDA’s priority review program, demonstrating its clinical importance.
Economic and social impact
Although Trastuzumab emtansine has shown good efficacy, its price has also caused controversy. In the UK, NICE did not recommend the drug because it was unable to reach an agreement on reasonable pricing. However, with an agreement reached between the two parties, the drug successfully returned to the medical system in 2017.
Future Outlook
As research continues to deepen, Trastuzumab emtansine still has the potential to continue to develop in two main directions. On the one hand, more clinical trials may be conducted in the future to further evaluate its use in first-line treatment; on the other hand, more optimized drug combinations may bring better therapeutic effects.
In this battle against cancer, the importance of Trastuzumab emtansine cannot be ignored. When we look back at the research progress over the years, can we expect that in the future there will be a breakthrough therapy like Trastuzumab emtansine to help more patients get rid of the shadow of cancer?
