Medical Editor: John P. Cunha, DO, FACOEP
What Is Margenza?
Margenza (margetuximab-cmkb) is a HER2/neureceptor antagonist indicated, in combination with chemotherapy, to treat adult patients with metastatic HER2-positive breast cancer who have received two or more prior anti-HER2 regimens, at least one of which was for metastatic disease.
What Are Side Effects of Margenza?
Side effects of Margenza in combination with chemotherapy include:
- fatigue,
- weakness,
- nausea,
- diarrhea,
- vomiting,
- constipation,
- headache,
- fever,
- hair loss,
- abdominal pain,
- numbness and tingling in extremities,
- joint or muscle pain,
- cough,
- decreased appetite,
- shortness of breath,
- infusion-related reactions,
- hand-foot syndrome (palmar-plantar erythrodysesthesia), and
- extremity pain
Dosage for Margenza
Margenza is administered as an intravenous infusion at 15 mg/kg over 120 minutes for the initial dose, then over a minimum of 30 minutes every 3 weeks for all subsequent doses.
Margenza In Children
The safety and effectiveness of Margenza have not been established in pediatric patients.
What Drugs, Substances, or Supplements Interact with Margenza?
Margenza may interact with other medicines such as:
- anthracyclines
Tell your doctor all medications and supplements you use.
Margenza During Pregnancy and Breastfeeding
Tell your doctor if you are pregnant or plan to become pregnant before using Margenza; it may harm a fetus. The pregnancy status of females of reproductive potential should be verified prior to initiation of Margenza. Women who received Margenza during pregnancy or within 4 months prior to conception should be monitored for too little amniotic fluid (oligohydramnios). Females of reproductive potential are advised to use effective contraception during treatment and for 4 months following the last dose of Margenza. It is unknown if Margenza passes into breast milk or how it would affect a nursing infant. Consult your doctor before breastfeeding.
Additional Information
Our Margenza (margetuximab-cmkb) Injection, for Intravenous Use Side Effects Drug Center provides a comprehensive view of available drug information on the potential side effects when taking this medication.
This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.
This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.
SLIDESHOW
Breast Cancer Awareness: Symptoms, Diagnosis, and Treatment See SlideshowSIDE EFFECTS
The following adverse reactions are discussed in greater detail in other sections of the label:
- Left Ventricular Dysfunction [see WARNINGS AND PRECAUTIONS]
- Embryo-Fetal Toxicity [see WARNINGS AND PRECAUTIONS]
- Infusion-Related Reactions [see WARNINGS AND PRECAUTIONS]
Clinical Trials Experience
Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect rates observed in practice.
The safety of MARGENZA was evaluated in HER2-positive breast cancer patients who received two or more prior anti-HER2 regimens in SOPHIA [see Clinical Studies].
Patients were randomized (1:1) to receive either MARGENZA 15 mg/kg every 3 weeks plus chemotherapy or trastuzumab plus chemotherapy. Among patients who received MARGENZA, 40% were exposed for 6 months or longer and 11% were exposed for greater than one year.
Serious adverse reactions occurred in 16% of patients who received MARGENZA. Serious adverse reactions in > 1% of patients included febrile neutropenia (1.5%), neutropenia/neutrophil count decrease (1.5%) and infusion related reactions (1.1%). Fatal adverse reactions occurred in 1.1% of patients who received MARGENZA, including viral pneumonia (0.8%) and aspiration pneumonia (0.4%).
Permanent discontinuation due to an adverse reaction occurred in 3% of patients who received MARGENZA. Adverse reactions which resulted in permanent discontinuation in > 1% of patients who received MARGENZA included left ventricular dysfunction and infusion related reactions.
Dosage interruptions due to an adverse reaction occurred in 11% of patients who received MARGENZA. Adverse reactions which required dosage interruption in > 5% of patients who received MARGENZA included infusion related reactions.
Table 1 summarizes the adverse reactions in SOPHIA.
Table 1 : Adverse Reactions (>10%) in Patients with Metastatic HER2-Positive Breast Cancer Who Received MARGENZA in SOPHIA
| Adverse Reaction | MARGENZA + Chemotherapy (n = 264) | Trastuzumab + Chemotherapy (n = 266) | ||
| All Grades (%) | Grade 3 or 4 (%) | All Grades (%) | Grade 3 or 4 (%) | |
| General disorders and administration site conditions | ||||
| Fatigue/Asthenia | 57 | 7 | 47 | 4.5 |
| Pyrexia | 19 | 0.4 | 14 | 0.4 |
| Gastrointestinal disorders | ||||
| Nausea | 33 | 1.1 | 32 | 0.4 |
| Diarrhea | 25 | 2.3 | 25 | 2.3 |
| Vomiting | 21 | 0.8 | 14 | 1.5 |
| Constipation | 19 | 0.8 | 17 | 0.8 |
| Abdominal paina | 17 | 1.5 | 21 | 1.5 |
| Skin and Subcutaneous tissue | ||||
| Alopecia | 18 | 0 | 15 | 0 |
| Palmar-plantar erythrodysesthesia | 13 | 0 | 15 | 3 |
| Nervous System Disorders | ||||
| Headacheb | 19 | 0 | 16 | 0 |
| Peripheral neuropathyc | 16 | 1.1 | 15 | 2.3 |
| Respiratory, thoracic and mediastinal disorders | ||||
| Cough | 14 | 0.4 | 12 | 0 |
| Dyspnea | 13 | 1.1 | 11 | 2.3 |
| Metabolism and nutrition disorders | ||||
| Decreased appetite | 14 | 0.4 | 14 | 0.4 |
| Musculoskeletal and connective tissue disorders | ||||
| Arthralgia/Myalgia | 14 | 0.4 | 12 | 0.8 |
| Extremity pain | 11 | 0.8 | 9 | 0 |
| a Includes abdominal pain, abdominal discomfort, lower abdominal pain and upper abdominal pain b Includes headache and migraine c Includes peripheral neuropathy, peripheral sensory neuropathy, peripheral motor neuropathy, and neuropathy | ||||
Clinically relevant adverse reactions in ≤10% of patients who received MARGENZA in combination with chemotherapy included: dizziness and stomatitis (10%) each, decreased weight, dysgeusia, rash, and insomnia (6%) each, hypertension (5%), and syncope (1.5%).
Table 2 summarizes the laboratory abnormalities in SOPHIA.
Table 2 : Select Laboratory Abnormalities (>20%) That Worsened from Baseline in Patients with Metastatic HER2-Positive Breast Cancer Who Received MARGENZA in SOPHIA
| Laboratory Abnormality | MARGENZA + chemotherapy1 | Trastuzumab + chemotherapy1 | ||
| All Grades (%) | Grade 3 or 4 (%) | All Grades (%) | Grade 3 or 4 (%) | |
| Hematology | ||||
| Decreased hemoglobin | 52 | 3.2 | 43 | 2.4 |
| Decreased leukocytes | 40 | 5 | 36 | 3.2 |
| Decreased neutrophils | 34 | 9 | 28 | 9 |
| Increased aPTT | 32 | 3.4 | 34 | 4.3 |
| Decreased lymphocytes | 31 | 4.4 | 38 | 4.4 |
| Increased INR | 24 | 1.2 | 25 | 0.4 |
| Chemistry | ||||
| Increased creatinine | 68 | 0.4 | 60 | 0 |
| Increased ALT | 32 | 2 | 30 | 0.8 |
| Increased lipase | 30 | 6 | 24 | 3.2 |
| Increased AST | 23 | 2 | 22 | 0.8 |
| Increased alkaline phosphatase | 21 | 0 | 23 | 0.8 |
| 1 The denominator used to calculate the rate varied from 229 to 253 based on the number of patients with a baseline value and at least one post-treatment value. aPTT: activated partial thromboplastin time; INR: prothrombin international normalized ratio; ALT: alanine aminotransferase; AST: aspartate aminotransferase | ||||
Immunogenicity
As with all therapeutic proteins, there is potential for immunogenicity with MARGENZA. The detection of antibody formation is highly dependent on assay sensitivity and specificity. Additionally, the observed incidence of antibody (including neutralizing antibody) positivity in an assay may be influenced by several factors including assay methodology, sample handling, timing of sample collection, concomitant medications, and underlying disease. For these reasons, comparison of the incidence of antibodies to MARGENZA in the studies described below with the incidence of antibodies in other studies or to other products may be misleading.
In SOPHIA, samples were obtained from patients on MARGENZA for immunogenicity testing at baseline, every 2 cycles, and at end of study therapy. All patients enrolled in SOPHIA received trastuzumab previously, and treatment-emergent anti-margetuximab antibodies were observed in 4 patients (1.7%). Of these 4 patients, anti-margetuximab antibodies were detected prior to Cycle 7 of MARGENZA dosing in 1 patient, and more than 2 months after the last MARGENZA dose in 3 patients. In the infusion substudy, treatment-emergent anti-margetuximab antibodies were observed in 2 patients (3.8%). Of these 2 patients, anti-margetuximab antibodies were detected prior to Cycle 3 of MARGENZA dosing in 1 patient, and more than 6 months after the last MARGENZA dose in 1 patient. Due to the limited number of patients who developed antimargetuximab antibodies during treatment with MARGENZA, the impact of anti-margetuximab antibodies on the PK, safety and efficacy of MARGENZA is unknown.
Read the entire FDA prescribing information for Margenza (Margetuximab-cmkb Injection, for Intravenous Use)
