What is targeted therapy?
Molecular targeted therapy means that the drug enters the body and specifically selects the cancer-causing sites at the molecular level to combine and act, causing the specific death of tumor cells without affecting the normal tissue cells around the tumor. Therefore, molecular targeted therapy is also called “biological missile”, which generally only has inhibitory effect on tumor and less side effects on normal tissues.
Does targeted therapy belong to chemotherapy?
Targeted therapy is essentially a kind of biological therapy, not chemotherapy, and there is an essential difference between the two. The chemotherapy drugs in the traditional sense mainly refer to cytotoxic drugs, which are chemicals with killing effect, besides having killing effect on tumor cells, they are also toxic to many normal tissue cells that also divide vigorously, such as: white blood cells, platelets, gastrointestinal mucosa, hair follicles and so on. Therefore, chemotherapy often causes some related side effects, such as: decrease in white blood cells, decrease in platelets, nausea and vomiting, hair loss, etc. Targeted therapy drugs theoretically target only tumor cells and have no effect or less effect on normal tissues, so they tend not to have chemotherapy-related side effects.
What are the types of molecular targeted therapeutic drugs used in clinical practice?
According to the target and nature of drug action, the main molecular targeted therapeutic drugs can be divided into the following categories.
(i) small molecule epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors, such as gefitinib and erlotinib.
(ii) Anti-epidermal growth factor receptor monoclonal antibodies, such as cetuximab.
(iii) Monoclonal antibodies against the proto-oncogene human epidermal growth factor receptor 2, such as trastuzumab.
(iv) Anti-vascular endothelial growth factor receptor (VEGFR) inhibitors, such as bevacizumab.
⑤ mammalian rapamycin target protein kinase inhibitor, everolimus.
(vi) Anti-CD20 monoclonal antibodies, such as rituximab.
What is HER-2? How is it detected and interpreted?
The Chinese name for HER-2 (C-erbB2) is human epidermal growth factor receptor-2. The main methods currently used to detect HER-2 are immunohistochemistry (IHC) and fluorescence immunohybridization (FISH), both of which have advantages and disadvantages. iHC method detects HER-2 protein with specific antibodies, while FISH method detects HER-2 gene amplification. iHC test IHC is simple, popular and inexpensive, but the results are more influenced by the specimen, reagents and technique, and are sometimes prone to false results; FISH is complex, expensive and not available in many hospitals, but the results are more accurate and objective. In general, all breast cancer specimens are tested for HER-2 by IHC method and the results are classified as -, +, ++, ++++, etc. – and + are usually defined as HER-2 negative, ++++ is defined as HER-2 positive (overexpression), while for +++, HER-2 may be negative or positive and needs to be FISH method for further verification. The results of the FISH method can be quantified and divided into no amplification and amplification, with patients without amplification defined as HER-2 negative and amplified patients defined as HER-2 positive.
What is the significance of HER-2 positivity?
HER-2 positivity is a bad indicator of increased risk of breast cancer recurrence and metastasis or poor outcome of some treatments. Such patients are usually given adjuvant chemotherapy after surgery, and chemotherapy combined with anti-HER-2 drugs such as trastuzumab can further improve the outcome.
Why do I need repeat HER-2 testing?
HER-2 test results are influenced by many factors, such as specimen fixation and sampling. In addition, the level of testing varies from one provider to another, which may lead to inconsistent results. Moreover, even for the same patient, the HER-2 results may vary from one tumor specimen to another, especially when the tumor has metastasized, the HER-2 results may change and the results may be different from those of the primary tumor. Therefore, repeat HER-2 testing is necessary in many cases and may give patients new opportunities for treatment and survival.
Which patients need to be treated with trastuzumab (Herceptin)?
Patients with HER-2-positive breast cancer may need to be treated with trastuzumab. HER-2 positivity includes HER-2 overexpression or amplification, i.e. HER-2 +++ by IHC or HER-2 gene amplification by FISH. About 25% of breast cancer patients are HER-2 positive, and these patients need to receive trastuzumab in two main situations: one is after radical surgery, and chemotherapy is used at the same time or after the end of chemotherapy, which is postoperative adjuvant therapy to prevent tumor recurrence; the other is after tumor recurrence and metastasis, which is usually combined with chemotherapy or endocrine therapy, with the purpose of The second one is used after tumor recurrence and metastasis, usually in combination with chemotherapy or endocrine therapy, in order to control tumor development, reduce the threat of tumor to life and prolong the survival of patients.
What is the efficacy of trastuzumab (Herceptin)?
The efficacy of trastuzumab is closely related to HER-2 status, with HER-2-positive patients having a significantly better outcome than negative patients. Therefore, trastuzumab treatment is not currently recommended for HER-2 negative patients. In HER-2 positive breast cancer patients, the use of trastuzumab can significantly improve the treatment outcome. Of course, the effectiveness of trastuzumab alone is low, below 20%, but in combination with chemotherapy or endocrine therapy, the effectiveness often exceeds 50%. In early stage patients without recurrence or metastasis, the use of trastuzumab for 1 year after surgery can significantly reduce the risk of recurrence by about 50%.
What are the side effects of trastuzumab (Herceptin)?
Trastuzumab is different from chemotherapy in that it has milder side effects. About 40% of patients will experience flu-like symptoms, such as fever and chills, for the first time, which are usually mild and mostly resolve on their own, especially for the first time, and need to be monitored closely. Trastuzumab is not recommended to be used again in the future once allergy has occurred.
Trastuzumab has a certain effect on the heart, with an incidence of 2% to 5%, most of which is only manifested by abnormalities in test indicators, and the patients themselves have no symptoms. It is generally recommended that cardiac function should be evaluated before and every 3-4 months during the course of drug use. Mild cardiotoxicity often resolves on its own after discontinuation and does not require special treatment, and most of them do not affect the continued use of trastuzumab in the future. Symptomatic cardiotoxicity is rare, but once it occurs, future use of trastuzumab is not recommended.
How is trastuzumab (Herceptin) used?
Trastuzumab is administered by intravenous infusion and the dose needs to be calculated based on the patient’s weight. The standard regimen currently recommended is an initial 4 mg/kg IV, followed by 2 mg/kg IV once a week. There is also a 3-week dosing regimen that is equivalent to weekly dosing, but with fewer and more convenient infusions for the patient, which is: 8 mg/kg IV initially, followed by 6 mg/kg IV every 3 weeks, once every 3 weeks.
Trastuzumab is currently available in China as a 440 mg lyophilized powder injection plus 20 ml of sterile water for injection containing special preservative ingredients. the solution configured with sterile water for injection delivered in trastuzumab packages can be stored for 28 days at 2-8°C and can be drawn several times for multiple use to avoid waste.
Is it impossible to stop using trastuzumab (Herceptin) once it has been used?
Trastuzumab is generally used in two situations, and the recommended duration of use varies. For patients with early stage post-operative breast cancer, the current recommended duration of treatment with trastuzumab to prevent recurrence is 1 year. For patients who have metastasized, there is in principle no limit to the duration of treatment and trastuzumab can be used continuously for a long time as long as the disease is controlled and trastuzumab has no significant side effects. Even if tumor progression occurs during trastuzumab treatment, it is currently believed that trastuzumab can be continued, as long as the combined chemotherapy or endocrine therapy regimen is changed.
Are there other targeted anti-HER-2 drugs available?
There are two main classes of anti-HER-2 drugs: antibodies, mainly trastuzumab, and small molecule compounds, represented by lapatinib. There are also a variety of other targeted anti-HER-2 therapeutic agents that have shown good therapeutic effects and may be available in the near future. These mainly include the antibody-based drug T-DM1, and the small molecule compounds Neratinib (HKI-272) and Afatinib (BIBW2992).
What are the side effects of Lapatinib?
Lapatinib is an oral drug with mild side effects, mainly rash, diarrhea and mild impaired liver function. Cardiac toxicity can occur in rare patients, but is less frequent and less severe than that of trastuzumab (Herceptin), and cardiac function often returns to normal on its own after stopping lapatinib.
What other targeted therapies can be used to treat breast cancer?
In addition to anti-HER-2 targeted drugs, there are many other drugs with other targets of action that can be used to treat breast cancer. Most of them are in the clinical research stage and are not yet widely used. Only bevacizumab and everolimus have been approved in some countries for the treatment of breast cancer.
What is the principle of action of bevacizumab?
Bevacizumab belongs to the category of anti-angiogenic drugs, and also belongs to a large group of tumor-targeted therapeutic drugs. It mainly inhibits tumor angiogenesis and interferes with tumor nutrient supply to “starve” the tumor. When tumor grows to a certain size, many small blood vessels will be created to provide more nutrition and oxygen for tumor growth. Therefore, controlling tumor neovascularization can theoretically achieve the ability to control tumor growth and metastasis. Bevacizumab is a monoclonal antibody against vascular endothelial growth factor, which is the key promoter of angiogenesis.
How does bevacizumab work?
Bevacizumab has shown some efficacy in the treatment of breast cancer. The efficacy of monotherapy in breast cancer is limited at 5% to 10%, but the combination with chemotherapy or other targeted therapies may further improve the efficacy. The more common combination drugs include chemotherapy drugs such as paclitaxel and vincristine and targeted drugs such as trastuzumab.
What are the side effects of bevacizumab?
The side effects of bevacizumab are mainly hypertension, proteinuria, bleeding disorders and thrombosis, which need to be closely monitored during use, especially for patients with related medical history.
Can all breast cancers be treated with targeted therapy?
The mechanism of action of targeted therapy is to target the target and then deliver a blow, therefore, only breast cancer with the corresponding target will be effective for the corresponding targeted therapy. Only when the right patient is selected and the right targeted therapy drug is used, it is possible to achieve the highly effective and less toxic therapeutic effect of targeted therapy. Therefore, targeted drugs are not effective for all breast cancers and should not be used blindly, otherwise it will delay the treatment time and also waste the treatment cost.