Trastuzumab (Herceptin)

General information

Class/mechanism: HER2/neu receptor antagonist, humanized IgG1 kappa monoclonal antibody. Trastuzumab binds to the extracellular domain of HER2/erbB2 (human epidermal growth factor receptor 2), which is overexpressed in certain malignancies. Trastuzumab helps to mediate antibody-dependent cellular cytotoxicity (ADCC) preferentially against cells that overexpress HER2.
Route: IV
Extravasation: neutral

For conciseness and simplicity, HemOnc.org currently will focus on treatment regimens and not list information such as: renal/hepatic dose adjustments, metabolism (including CYP450), excretion, monitoring parameters (although this will be considered for checklists), or manufacturer. Instead, for the most current information, please refer to your preferred pharmacopeias such as Micromedex, Lexicomp, UpToDate (courtesy of Lexicomp), or the prescribing information.

Special considerations

• Trastuzumab use is contraindicated during pregnancy.

Diseases for which it is established

• HER2+ breast cancer
• HER2+ colon cancer
• HER2+ gastric cancer

Diseases for which it is used

• Endometrial cancer
• HER2+ esophageal cancer
• HER2+ tumors (site-agnostic)

Patient drug information

• Trastuzumab (Herceptin) manufacturer's patient website
• Trastuzumab (Herceptin) patient drug information (Chemocare)
• Trastuzumab (Herceptin) patient drug information (UpToDate)

History of changes in FDA indication

HER2+ breast cancer

• 1998-09-25: Initial FDA approval as a single agent for treatment of patients with metastatic breast cancer whose tumors overexpress the HER2 protein and who have received one or more chemotherapy regimens for their metastatic disease. (Based on Cobleigh et al. 1999)
• 2002-08-28: Approved in combination with paclitaxel for treatment of patients with metastatic breast cancer whose tumors overexpress the HER2 protein and who have not received chemotherapy for their metastatic disease. (Approval extended to first-line metastatic setting; based on Slamon et al. 2001)
• 2006-11-16: Label revised: trastuzumab as part of a treatment regimen containing doxorubicin, cyclophosphamide, and paclitaxel is indicated for the adjuvant treatment of patients with HER2-overexpressing, node-positive breast cancer. (Approval extended to adjuvant setting; based on BCIRG 006, HERA, NCCTG N9831, NSABP B-31)
• 2008-01-18: Labeling simplified: indicated for the treatment of HER2 overexpressing breast cancer. (Approval extended to all settings)

HER2+ gastric/gastroesophageal cancer

• 2010-10-20: Approved in combination with cisplatin and a fluoropyrimidine (capecitabine or 5-fluorouracil), for the treatment of patients with HER2 overexpressing metastatic gastric or gastroesophageal (GE) junction adenocarcinoma, who have not received prior treatment for metastatic disease. (New disease entity; based on ToGA)

History of changes in EMA indication

• 2000-08-28: Initial market authorization as Herceptin. Herceptin is indicated for the treatment of patients with metastatic breast cancer whose tumours overexpress HER2: in combination with paclitaxel for the treatment of those patients who have not received chemotherapy for their metastatic disease and for whom an anthracycline is not suitable.
• 2000-08-28: Herceptin is indicated for the treatment of patients with metastatic breast cancer whose tumours overexpress HER2: as monotherapy for the treatment of those patients who have received at least two chemotherapy regimens for their metastatic disease. Prior chemotherapy must have included at least an anthracycline and a taxane unless patients are unsuitable for these treatments. Hormone receptor positive patients must also have failed hormonal therapy, unless patients are unsuitable for these treatments.
• 2006-05-22: Extension of indication for use in patients with HER2-positive with HER2-positive early breast cancer.
• 2010-01-19: Extension of indication for use in combination with capecitabine or 5-fluorouracil and cisplatin for the treatment of patients with HER2-positive metastatic adenocarcinoma of the stomach or gastro-esophageal junction who have not received prior anti-cancer treatment for their metastatic disease.
• 2011-04-20: Extension of indication to include concurrent use of Herceptin with chemotherapy in the adjuvant treatment of patients with HER2-positive early breast cancer as part of a treatment regimen consisting of doxorubicin and cyclophosphamide followed by combination with paclitaxel or docetaxel, or as part of a treatment regimen in combination with docetaxel and carboplatin.
• 2011-12-19: Extension of indication to include treatment of patients with HER2-positive early breast cancer in combination with neoadjuvant chemotherapy, followed by adjuvant trastuzumab monotherapy, for locally advanced (including inflammatory) breast cancer or tumours greater than 2 cm in diameter.

History of changes in PMDA indication

• 2008-02-29: New indication and dosage for use as a postoperative adjuvant chemotherapy in patients with HER2-overexpressing breast cancer.
• 2011-03-10: New additional indication and a new dosage for the treatment of unresectable advanced or recurrent gastric cancer with HER2 overexpression.
• 2011-11-25: New additional indication and a new dosage for the treatment of breast cancer with HER2 overexpression.
• 2021-11-25: New indication and a new dosage for the treatment of unresectable advanced or recurrent HER2-positive salivary gland tumors.
• 2022-03-28: New indication and a new dosage for the treatment of unresectable advanced or recurrent HER2-positive colon or rectal cancer that has progressed after cancer chemotherapy.

Also known as

• Brand names: Biceltis, CANMab, Herceptin, Herclon, Hertraz