MARGETUXIMAB-CMKB INJ,SOLN

Clinical Criteria Summary

• Treatment, in combination with chemotherapy, of 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.

• Dosage form: 250 mg/10 mL single-dose vial.
• Dose: 15 mg/kg IV every 3 weeks (21-day cycle) until disease progression or unacceptable toxicity.
• Initial dose administered over 120 minutes; subsequent doses over a minimum of 30 minutes.
• May be administered immediately after chemotherapy completion on days co-administered with chemotherapy.

• Left ventricular dysfunction (LVD): Withhold for at least 4 weeks for ≥16% absolute decrease in LVEF from pretreatment values, or LVEF below institutional limits of normal (or 50% if no limits) and ≥10% absolute decrease. May resume if LVEF returns to normal limits and absolute decrease ≤15% within 8 weeks. Permanently discontinue if LVEF decline persists >8 weeks or dosing interrupted >3 occasions for LVEF decline.
• Infusion-related reactions: Decrease infusion rate for mild or moderate reactions; interrupt for dyspnea or clinically significant hypotension; discontinue for severe or life-threatening reactions. Consider premedications (antihistamines, corticosteroids, antipyretics) for mild/moderate reactions.
• Exclusions/Not Studied: Patients with pretreatment LVEF <50%, prior history of myocardial infarction or unstable angina within 6 months, or congestive heart failure NYHA class II-IV.

• Common adverse reactions (≥20%): Fatigue/asthenia, nausea, diarrhea, vomiting, decreased hemoglobin, decreased leukocytes, decreased neutrophils, increased aPTT, decreased lymphocytes, increased INR, increased creatinine, increased ALT, increased lipase, increased AST, increased alkaline phosphatase.
• Serious adverse events: Grade 5 fatal events reported (viral and aspiration pneumonia); none considered treatment-related. Permanent discontinuation due to adverse events occurred in 3% of patients (left ventricular dysfunction, infusion-related reaction). Dosage interruptions occurred in 11% of patients.
• Embryo-fetal toxicity: Can cause fetal harm when administered to pregnant women.

• Select patients for treatment based on the presence of ERBB-2 mutation in tumor sample.
• Not included in the VHA clinical pathway for breast cancer due to lack of overall survival benefit compared to trastuzumab + chemotherapy, along with associated toxicity and expense.

Tumor tissue does not overexpress HER2 protein (Defined as IHC 3+ or FISH amplification ratio greater than or equal to 2.0)
Known hypersensitivity to margetuximab or any of its excipients (e.g., polysorbate 80, sucrose)
Untreated and/or unstable brain metastases
Myocardial infarction, unstable angina, stroke, or transient ischemic attack within 6 months of start
Clinically significant cardiac arrhythmia requiring treatment
Uncontrolled hypertension (>180/100 mmHg)
History of congestive heart failure (New York Heart Association Class 2-4)
Baseline left ventricular ejection fraction <50%
Pericarditis, myocarditis or significant pericardial effusion
Severe renal impairment (defined as CrCl less than 29 ml/min)
Moderate or severe hepatic impairment (defined as total bilirubin > 1.5 times the upper limit of normal and any AST)
Pregnancy
Lactating

Diagnosis of metastatic breast cancer
Received 2 or more prior anti-HER2 regimens, with at least one provided in the metastatic setting

Care for the oncologic condition provided by VA or VA Community Care oncology provider
Goals of care and role of Palliative Care consult have been discussed and documented
Eastern Cooperative Oncology Group (ECOG) Performance Status 0 to 1

For patients who may become pregnant: Counseling provided on potential risks vs benefits of treatment and the use of effective contraception during therapy and for 7 months after the last dose of margetuximab