Indications

• HER2+ Breast Cancer (see Breast Cancer, [[Breast Cancer]])
  • Adjuvant Therapy for HER-2+ Breast Cancer
  • Neoadjuvant Therapy for Early-Stage Locally Advanced, or Inflammatory HER-2+ Breast Cancer: off-label
  • Metastatic HER2+ Breast Cancer: alone or in combination with paclitaxel
• Metastatic HER2+ Gastric Cancer (see Gastric Cancer, [[Gastric Cancer]]): in combination with cisplatin and either capecitabine or 5-fluorouracil

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Contraindications

• Pregnancy (see Pregnancy, [[Pregnancy]]): due to risk of oligohydramnios and oligohydramnios sequence (pulmonary hypoplasia, skeletal malformations, and neonatal death)

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Pharmacology

• Monoclonal Antibody Binds to the Extracellular Domain of the HER2: it mediates antibody-dependent cellular cytotoxicity by inhibiting proliferation of cells which overexpress the HER2 protein

Background on ErbB Family of Receptors

• General Comments: this is a family of closely-related epidermal growth factor receptor tyrosine kinases
  • Human Epidermal Growth Factor Receptor = HER
• Family Members
  • Epidermal Growth Factor Receptor (EGFR): also called HER1 or ErbB-1
  • HER2/neu: also called ErbB-2 or CD340
  • HER3: also called ErbB-3
  • HER4: also called ErbB-4

Metabolism

• Washout: in most cases, trastuzumab concentrations will decrease to approximately 3% (approximately 97% washout) by 7 mo after discontinuation

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Administration

• IV

Dose Adjustment

• Hepatic: none
• Renal: none

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Adverse Effects

Allergic Adverse Effects

Anaphylaxis (see Anaphylaxis, [[Anaphylaxis]])

• Epidemiology: occurs in <1% of cases

Cardiovascular Adverse Effects

Cardiomyopathy/Congestive Heart Failure (CHF) (see Congestive Heart Failure, [[Congestive Heart Failure]])

• Epidemiology: occurs in 4-22% of cases
  • Highest Risk: when used in combination with anthracyclines
• Clinical
  • Systolic Congestive Heart Failure

Pulmonary Adverse Effects

Acute Respiratory Distress Syndrome (ARDS) (see Acute Respiratory Distress Syndrome, [[Acute Respiratory Distress Syndrome]])

• Epidemiology: occurs in <1% of cases

Acute or Subacute Interstitial Pneumonitis (see Interstitial Lung Disease, [[Interstitial Lung Disease]])

• Epidemiology: occurs in 0.5% of cases
• Prognosis: 0.1% mortality rate

Other Adverse Effects

Infusion Reaction

• Epidemiology: occurs in 21-40% of cases
  • Occurs during or within 24 hrs of the first intravenous infusion
• Clinical
  • Angioedema (see Angioedema, [[Angioedema]])
  • Bronchospasm (see Obstructive Lung Disease, [[Obstructive Lung Disease]])
  • Chills
  • Dizziness (see Dizziness, [[Dizziness]])
  • Dyspnea (see Dyspnea, [[Dyspnea]])
  • Fever (see Fever, [[Fever]])
  • Headache (see Headache, [[Headache]])
  • Hypotension (see Hypotension, [[Hypotension]])
  • Nausea/Vomiting (see Nausea and Vomiting, [[Nausea and Vomiting]])
  • Pain
  • Rash
  • Weakness

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References

• Risk of heart failure in breast cancer patients after anthracycline and trastuzumab treatment: a retrospective cohort study. J Natl Cancer Inst. 2012;104(17):1293-1305 [MEDLINE]
• Trastuzumab-Associated Cardiac Events at 8 Years of Median Follow-Up in the Herceptin Adjuvant Trial (BIG 1-01). J Clin Oncol. 2014;32(20):2159-2165 [MEDLINE]