Trastuzumab (Herceptin)

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

Contraindications

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

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

Administration

  • IV

Dose Adjustment

  • Hepatic: none
  • Renal: none

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

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]