Early in 2019, trastuzumab-dttb was approved as a biosimilar to standard trastuzumab for treatment of HER2-expressing breast cancer in the adjuvant setting, metastatic breast cancer, and metastatic gastric cancer or gastroesophageal junction adenocarcinoma in patients who have not received prior treatment for metastatic disease.1
Trastuzumab-dttb is indicated for treatment of the following cancers:
Adjuvant treatment of HER2-overexpressing node-positive or node-negative (estrogen receptor–progesterone receptor–negative or with one high risk feature) breast cancer:
Treatment of metastatic breast cancer:
Treatment of metastatic gastric cancer:
Patients must be selected for therapy based on a U.S. Food and Drug Administration (FDA)-approved companion diagnostic for a trastuzumab product. Health-care professionals should review product labeling for detailed information on the use of trastuzumab-dttb, which should not be substituted for or with ado-trastuzumab emtansine.
Biosimilarity of trastuzumab-dttb has been demonstrated for the condition(s) of use (eg, indication(s), dosing regimen(s), strength(s), dosage form(s), and route(s) of administration described in its full prescribing information. 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-dttb is a biosimilar to the U.S. standard trastuzumab.
Trastuzumab-dttb 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. An interchangeable product may be substituted for a reference product without the involvement of the prescriber.
The recommended dosage and administration of trastuzumab-dttb follows:
Adjuvant treatment of HER2-overexpressing breast cancer:
Administer according to one of the following doses and schedules for a total of 52 weeks of trastuzumab-dttb therapy:
During and following paclitaxel, docetaxel, or docetaxel and carboplatin:
As a single agent within 3 weeks following completion of multimodality, anthracycline-based chemotherapy regimens:
Treatment of Metastatic Breast Cancer:
Treatment of metastatic gastric cancer:
As with standard trastuzumab, the most common expected adverse events with trastuzumab-dttb (≥ 5%) in the adjuvant treatment of breast cancer are headache, diarrhea, nausea, and chills. The most common adverse events in metastatic breast cancer (≥ 10%) are fever, chills, headache, infection, congestive heart failure, insomnia, cough, and rash. The most common adverse events in metastatic gastric cancer (≥ 10%) are neutropenia, diarrhea, fatigue, anemia, stomatitis, weight loss, upper respiratory tract infections, fever, thrombocytopenia, mucosal inflammation, nasopharyngitis, and dysgeusia.
Like standard trastuzumab, the labeling for trastuzumab-dttb contains a boxed warning for increased risks of cardiomyopathy, infusion reactions, pulmonary toxicity, and embryofetal toxicity. Like standard trastuzumab, trastuzumab-dttb carries additional warnings and precautions for exacerbation of chemotherapy-induced neutropenia. The pregnancy status of women must be verified prior to initiation of trastuzumab-dttb.
1. Ontruzant (trastuzumab-dttb) for injection prescribing information, Merck Sharp & Dohme Corp, January 2019. Available at www.accessdata.fda.gov/drugsatfda_docs/label/2019/761100s000lbl.pdf. Accessed September 20, 2019.