Trastuzumab

Trastuzumab, sold under the brand name Herceptin among others, is a monoclonal antibody used to treat breast cancer. Specifically it is used for breast cancer that is HER2 receptor positive. It may be used by itself or together with other chemotherapy medication. Trastuzumab is given by slow injection into a vein and injection just under the skin.RET inhibitors: Vandetanib (also VEGFR and EGFR). Entrectinib (ALK, ROS1, NTRK).c-MET inhibitor: Cabozantinib (also VEGFR2).'-mexi-' (melanoma): Ecromeximab§ Trastuzumab, sold under the brand name Herceptin among others, is a monoclonal antibody used to treat breast cancer. Specifically it is used for breast cancer that is HER2 receptor positive. It may be used by itself or together with other chemotherapy medication. Trastuzumab is given by slow injection into a vein and injection just under the skin. Common side effects include fever, infection, cough, headache, trouble sleeping, and rash. Other severe side effects include heart failure, allergic reactions, and lung disease. Use during pregnancy may harm the baby. Trastuzumab works by binding to the HER2 receptor and slowing down cell duplication. Trastuzumab was approved for medical use in the United States in 1998. It is on the World Health Organization's List of Essential Medicines, the most effective and safe medicines needed in a health system. As of 2014, the wholesale price in the developing world is between US$1,800 and US$1,955 per 440 mg vial. In the United Kingdom a 150 mg vial costs the NHS £407.00. A biosimilar was approved in the United States in 2018. The safety and efficacy of trastuzumab-containing combination therapies (with chemotherapy, hormone blockers, or lapatinib) for the treatment of metastatic breast cancer. The overall hazard ratios for overall survival and progression free survival were 0.82 and 0.61, respectively. It was difficult to accurately ascertain the true impact of trastuzumab on survival, as in three of the seven trials, over half of the patients in the control arm were allowed to cross-over and receive trastuzumab after their cancer began to progress. Thus, this analysis likely underestimates the true survival benefit associated with trastuzumab treatment in this population. In these trials, trastuzumab also increased the risk of heart problems, including heart failure and left ventricular ejection fraction decline. In early stage (curable) HER2-positive breast cancer, trastuzumab-containing regimens improved overall survival (HR = 0.66) and disease-free survival (HR = 0.60). Increased risk of heart failure (RR = 5.11) and decline in left ventricular ejection fraction (RR = 1.83) were seen in these trials as well. Two trials involving shorter term treatment with trastuzumab did not differ in efficacy from longer trials, but produced less cardiac toxicity. The original studies of trastuzumab showed that it improved overall survival in late-stage (metastatic) HER2-positive breast cancer from 20.3 to 25.1 months. In early stage HER2-positive breast cancer, it reduces the risk of cancer returning after surgery. The absolute reduction in the risk of cancer returning within 3 years was 9.5%, and the absolute reduction in the risk of death within 3 years was reduced by 3%. However, it increases serious heart problems by an absolute risk of 2.1%, though the problems may resolve if treatment is stopped. Trastuzumab has had a 'major impact in the treatment of HER2-positive metastatic breast cancer.' The combination of trastuzumab with chemotherapy has been shown to increase both survival and response rate, in comparison to trastuzumab alone. It is possible to determine the 'erbB2 status' of a tumor, which can be used to predict efficacy of treatment with trastuzumab. If it is determined that a tumor is overexpressing the erbB2 oncogene and the patient has no significant pre-existing heart disease, then a patient is eligible for treatment with trastuzumab. It is surprising that although trastuzumab has great affinity for HER2 and high doses can be administered (because of its low toxicity), 70% of HER2+ patients do not respond to treatment. In fact resistance to the treatment develops rapidly, in virtually all patients. A mechanism of resistance involves failure to downregulate p27 (Kip1) as well as suppressing p27 translocation to the nucleus in breast cancer, enabling cdk2 to induce cell proliferation. The optimal duration of add-on trastuzumab treatment after surgery for early breast cancer is currently unknown. One year of treatment is generally accepted based on current clinical trial evidence that demonstrated the superiority of one-year treatment over none. However, a small Finnish trial also showed similar improvement with nine weeks of treatment over no therapy. Because of the lack of direct head-to-head comparison in clinical trials, it is unknown whether a shorter duration of treatment may be just as effective (with fewer side effects) than the currently accepted practice of treatment for one year. Debate about treatment duration has become a relevant issue for many public health policy makers because administering trastuzumab for a year is very expensive. Consequently, some countries with a taxpayer-funded public health system, such as New Zealand, chose to fund limited adjuvant therapy. However, subsequently New Zealand has revised its policy and now funds trastuzumab treatment for up to 12 months.