How is the drug name pronounced?
What cancer(s) does this drug treat?
Metastatic Breast Cancer
Margenza is approved for:
- Patients with breast cancer that tests positive for the HER2 molecule and has spread to other parts of the body (metastasized), and who have received two or more prior treatments that target the HER2 molecule, at least one of which was for their advanced disease. In such cases, Margenza is given in combination with chemotherapy.
Limitations of Use
Age: The safety and efficacy of Margenza in patients under 18 years of age have not been established.
Pregnancy/Breastfeeding: Margenza can cause harm to a fetus, and is not recommended for use during pregnancy. Women are advised to use contraception during treatment with Margenza and for at least 4 months after the last dose of Margenza. Women who receive Margenza while pregnant or within 4 months before conception should be monitored for any signs of an insufficient volume of the amniotic fluid. The risks associated with Margenza treatment during breastfeeding are not known and cannot be ruled out. Due to the potential for adverse reactions in the breastfed child, the treatment needs of the mother must be carefully weighed against the benefits of breastfeeding during treatment with Margenza and within 4 months after the last dose of Margenza.
Drug interactions: Treatment with anthracycline-based chemotherapy (e.g., doxorubicin) should be avoided for up to 4 months after stopping Margenza. Patients who receive anthracycline-based chemotherapy less than 4 months after stopping Margenza may be at increased risk to develop heart problems.
What type of immunotherapy is this?
- Cell growth inhibitor
How does this drug work?
- Human epidermal growth factor receptor 2 (HER2)
Margenza is an antibody that was made in the laboratory and designed to attach to a protein molecule called HER2. HER2 is present on the surface of some normal cells in the body, and it is also present in much higher quantities on the surface of breast cancer cells. Higher-than-normal amounts of HER2 on cancer cells make these cells the main target of Margenza.
Margenza and other antibodies have an overall “Y” shape. The two tips of the upper arms of the “Y” shape are the parts of the antibody that can very precisely bind to their targets. For Margenza, the tips of the upper arms bind to HER2. The stem of Margenza’s “Y” shape can attract immune cells or other parts of the immune system.
Margenza works to kill HER2-positive cancer cells in at least two ways.
Cancer cell growth inhibition
When HER2 on the surface of cells binds to itself or to other HER2-related proteins, it sends signals into the cell. These signals cause the cell to multiply, or in other ways promote the cell’s survival (such as by causing cancer cells to produce molecules that enhance the growth of blood vessels, which help feed the tumor and support its growth). Higher-than-normal amounts of HER2 allow cancer cells to grow and multiply out of control. Binding of Margenza to HER2 blocks HER2 from pairing up and sending these signals into the cancer cells, preventing the cells from persisting and multiplying. In addition, Margenza prevents cancer cells from “shedding” the HER2 molecules on their cell membranes. This may increase the action of Margenza on HER2-positive breast cancer cells.
Antibody-dependent cell-mediated cytotoxicity (ADCC)
When bound to HER2 on the surface of cancer cells, the stem of Margenza can also attract and bind immune cells (like NK cells). This allows Margenza to act as a bridge between the target cell and the immune cell. The immune cell then releases molecules that can kill the cell that Margenza is bound to. Margenza is very similar to trastuzumab (Herceptin), but Margenza’s stem has been modified in the laboratory to increase the ADCC activity of Margenza compared to trastuzumab.
How is this drug given to the patient?
Margenza is administered through a tube in the vein (intravenous infusion or i.v.). The first dose of Margenza is given over the course of 2 hours. Subsequent doses of Margenza are delivered over the course of at least half an hour every 3 weeks until the disease progresses or the side effects become unmanageable. On days when both Margenza and chemotherapy are to be administered, Margenza may be administered immediately after chemotherapy completion.
Prior to the starting treatment with Margenza, patients undergo a thorough assessment of the condition of their heart. Patients will also have their hearts monitored every 3 months during treatment with Margenza and upon completion of Margenza treatment.
What are the observed clinical results?
Metastatic Breast Cancer
In a clinical trial, 536 patients with with breast cancer that had spread to other parts of the body and tested positive for the HER2 molecule, and who had received prior treatment that targeted the HER2 molecule, were either treated with Margenza or trastuzumab (Herceptin), alongside chemotherapy (investigator’s choice of capecitabine, eribulin, gemcitabine, or vinorelbine).
What are the potential side effects?
The most common side effects of Margenza in combination with chemotherapy include weakness, fatigue, nausea, vomiting, constipation, diarrhea, headache, fever, hair loss, abdominal pain, muscle and joint pain, pain in the extremities, nerve damage (numbness, weakness, and pain in the hands and feet), hand-foot syndrome (tingling, tenderness, redness, swelling and pain primarily on the palm of the hand and sole of the foot), rash, coughing, difficulty breathing, and infusion-related reactions.
Margenza can cause heart problems – in particular, decreased function of the heart’s left ventricle, which is responsible for pumping oxygenated blood to the vital organs of the body. Prior to starting treatment with Margenza, patients undergo a thorough assessment of the condition of their heart. Patients also have their hearts monitored every 3 months during treatment with Margenza and upon completion of Margenza treatment. Treatment with Margenza is discontinued if severe heart issues occur.
Infusion-related reactions are side effects related to receiving an infusion. Most infusion-related reactions typically occur within 24 hours of the first or second infusion. Symptoms may include fever, chills, joint pain, dizziness, nausea, vomiting, headache, sweating, fast heartbeat, low blood pressure, ichting, rash, and difficulty breathing. A healthcare provider should be immediately notified if symptoms occur. Patients who have experienced infusion-related reactions may be treated with antihistamines, corticosteroids, and a fever reducer shortly before administration of subsequent doses of Margenza.
Patients should report any symptoms to their healthcare provider, who can then initiate actions to limit or reverse the side effects. For a more complete list of possible side effects, see the full prescribing information.
Links to drug website
- [Abstract GS1-02: Phase 3 SOPHIA study of margetuximab + chemotherapy vs trastuzumab + chemotherapy in patients with HER2+ metastatic breast cancer after prior anti-HER2 therapies: second interim overall survival analysis. Rugo, HS et al. Cancer Research (2020) ](<* https://cancerres.aacrjournals.org/content/80/4_Supplement/GS1-02>)