In recent times, the Russia-Ukraine war has affected the hearts of millions of people. Russia has adopted a precise strike strategy to target military targets in Ukraine, trying to avoid harming innocent people. This has given everyone more understanding while condemning Russia's invasion of the sovereign country of Ukraine.
Just like after the human body suffers from cancer, chemotherapy is a helpless move. However, while ordinary chemotherapy drugs attack cancer, they also have an "indiscriminate attack" on the body, causing great pain to patients and causing many patients to change their mind when talking about "chemotherapy."
If there are "precision attack" drugs for cancer, the damage of chemotherapy drugs to normal cells can be greatly reduced. In recent years, in the field of breast cancer treatment, ADC drugs that conform to the concept of "precision treatment" have emerged.
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01 Understanding ADC drugs
ADC is an antibody-drug conjugate (Antibody-drug Conjugate), which consists of three parts: monoclonal antibodies, cytotoxic drugs, and connectors.
Antibody conjugate drugs are like nuclear missiles equipped with automatic positioning systems. It has two core functional components: the first is an antibody (with positioning function), and the second is a powerful chemotherapeutic drug (nuclear warhead). The two are combined together through a special linker, combining the targeting properties of antibody drugs and the powerful killing power of chemotherapy drugs.
Just like a nuclear missile can accurately deliver a nuclear warhead to the target and detonate through the navigation system, after the antibody-conjugated drug enters the body, the antibody part recognizes the special proteins on the surface of the cancer cells, thereby delivering powerful chemotherapy drugs to the tumor in a targeted manner. part, so that while killing cancer cells, you can try to avoid harming normal cells.
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Currently, the ADC drugs that have been clinically used include T-DM1 (trastuzumab-metansin conjugate).
02 Introduction T-DM1
T-DM1 is an upgraded version of Herceptin. Popularly understood, it is Herceptin loaded with chemotherapy drugs.
As we all know, Herceptin (Trastuzumab Trastuzumab) is a targeted drug for the treatment of HRE2-positive breast cancer. On the basis of Herceptin, the small molecule cytotoxin DM1, a microtubule inhibitor chemotherapy drug, is loaded to form a T-DM1 complex, which achieves precise super-energy strikes in killing cancer cells.
At present, T-DM1 has been widely used clinically. is suitable for: (1) HER2-positive metastatic breast cancer, patients who have previously received trastuzumab and a taxane separately or in combination. ; (2) For HER2-positive early breast cancer, trastuzumab is used during adjuvant chemotherapy if pCR has not been achieved using neoadjuvant chemotherapy.
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3 The recommended status of T-DM1 in major guidelines
KATHERINE study is an international, multi-center, randomized, phase III clinical trial, including a total of 1486 patients, as a neoadjuvant use of trastuzumab HER2-positive breast cancer that has not achieved pCR after treatment will be randomly assigned in a 1:1 ratio to receive 14 cycles of T-DM1 treatment or 14 cycles of trastuzumab treatment. The primary endpoint is iDFS (invasive disease-free survival), and secondary endpoints include DFS, OS, and DRFI (distant recurrence interval). The results of the
study show that compared with trastuzumab, T-DM1 can reduce the risk of recurrence or death by 50%, improve 3-year DFS by 11.3%, and improve the freedom from invasion in patients with HER2-positive early breast cancer with residual disease after neoadjuvant treatment. breast cancer recurrence survival rate, and no new safety issues emerged.
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Due to the good performance of T-DM1 in the KATHERINE study, major guidelines have strongly recommended T-DM1.
1. In the NCCN guidelines, T-DM1 is considered as one of the first-line options for HER2-positive advanced breast cancer.
2. In the NCCN guidelines, T-DM1 is recommended as a category 1 adjuvant treatment for HER2-positive breast cancer with residual disease after neoadjuvant treatment.
3. According to the 2021 CSCO guidelines, only trastuzumab is used in the neoadjuvant setting for HER2-positive breast cancer, and for people who have not reached pCR, T-DM1 is recommended first, level I.
4. In the CSCO guidelines, T-DM1 is used as a second-line option for HER2-positive breast cancer after resistance to the first-line Herceptin regimen.
4 Adverse Reactions
The adverse reactions of T-DM1 are generally controllable. The most common side effects are: nausea, vomiting, thrombocytopenia, anemia, elevated liver enzymes, etc. The incidence rate is less than 5%. As long as the use is closely monitored, it is still possible. Relatively safe.
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The Russian-Ukrainian war is still going on, and the war between humans and cancer is far from over. They are killing each other. We look forward to the day in the near future when we can shake hands and make peace.
Reference:
1. Trastuzumab Emtansine for Residual Invasive HER2-Positive Breast Cancer. N Engl J Med 2019; 380:617-628
2. Pathological complete response and long-term clinical benefit in breast cancer: the CTNeoBC pooled analysis. Lancet. 2014 Jul 12;384(9938):164-72.
3. "2021 CSCO Breast Cancer Guidelines", Chinese Society of Clinical Oncology
4. NCCN Breast Cancer Guidelines Version 1.2019
