ON DECEMBER 14, 2018, trastuzumab-pkrb (Herzuma) was approved as a biosimilar to trastuzumab for patients with HER2-overexpressing breast cancer.1 Trastuzumab-pkrb is indicated for adjuvant treatment of HER2-overexpressing breast cancer and metastatic HER2-overexpressing breast cancer.2 Health-care professionals should review the product labeling for detailed information on the use of trastuzumab-pkrb.
Patients should be selected for treatment based on a U.S. Food and Drug Administration (FDA)-approved companion diagnostic for a standard trastuzumab product. HER2 testing should be performed using FDA-approved tests by laboratories with demonstrated proficiency. Trastuzumab-pkrb should not be substituted for or with trastuzumab emtansine.
Approval Process
BIOSIMILARITY OF trastuzumab-pkrb has been demonstrated for the condition(s) of use. The approval was based on comparisons of extensive structural and functional product characterization, animal data, human pharmacokinetic, clinical immunogenicity, and other clinical data demonstrating that trastuzumab-pkrb is biosimilar to the U.S. standard trastuzumab.
Trastuzumab-pkrb has been approved as a biosimilar, not as an interchangeable product. As defined by the FDA, a biosimilar “is a biological product that is highly similar to and has no clinically meaningful differences from an existing FDA-approved reference product.”
To satisfy the criteria of having no clinically meaningful differences, a manufacturer of a biosimilar product must demonstrate the absence of such differences from the reference product in terms of safety, purity, and potency (safety and effectiveness). This is generally demonstrated through human pharmacokinetic and pharmacodynamic studies; an assessment of clinical immunogenicity; and, if needed, additional clinical studies.
Recommended Dosing
THE RECOMMENDED dosage and administration of trastuzumab-pkrb follow:
Adjuvant Treatment of HER2-Overexpressing Breast Cancer: The initial dose is 4 mg/kg over a 90-minute intravenous (IV) infusion, then 2 mg/kg over a 30-minute IV infusion weekly for 12 weeks (with paclitaxel or docetaxel) or 18 weeks (with docetaxel and carboplatin). One week after the last weekly dose of trastuzumab-pkrb, 6 mg/kg as an IV infusion should be given over 30 to 90 minutes every 3 weeks, to complete a total of 52 weeks of therapy. (Product labeling for paclitaxel, docetaxel, and carboplatin should be consulted for recommended dosing.)
Metastatic HER2-Overexpressing Breast Cancer: The initial dose is 4 mg/kg as a 90-minute IV infusion followed by subsequent weekly doses of 2 mg/kg as 30-minute IV infusions.
Safety
AS WITH STANDARD trastuzumab, common expected side effects of trastuzumab-pkrb for the treatment of HER2-positive breast cancer include headache, diarrhea, nausea, chills, fever, infection, congestive heart failure, insomnia, cough, and rash. Serious expected side effects of trastuzumab-pkrb include worsening of chemotherapy-induced neutropenia.
As with standard trastuzumab, the labeling for trastuzumab-pkrb contains a boxed warning for increased risks of cardiomyopathy, infusion reactions, pulmonary toxicity, and embryofetal toxicity, as well as additional warnings and precautions for exacerbation of chemotherapy-induced neutropenia. The pregnancy status of women must be verified prior to the initiation of trastuzumab-pkrb. ■
REFERENCES
1. U.S. Food and Drug Administration: FDA approves Herzuma as a biosimilar to Herceptin. Available at www.fda.gov/Drugs/InformationOnDrugs/ApprovedDrugs/ ucm628724.htm. Accessed March 7, 2019.
2. Herzuma (trastuzumab-pkrb) for injection, prescribing information, Celltrion, Inc, December 21, 2018. Available at www.accessdata.fda.gov/drugsatfda_docs/label/2018/761091s000lbl.pdf. Accessed March 7, 2019.
