Reference, Biosimilar Trastuzumab Have Similar Antitumor Activity When Combined With Subdomain II Antibody

It is understood that the human epidermal growth factor receptor (HER) plays a key role in the proliferation and survival of cancer cells, and trastuzumab, which targets HER2, binds to subdomain IV of the HER2 extracellular domain.

Pertuzumab (Perjeta), subdomain II—targeting therapeutic antibody, binds to a different region of the same protein and blocks ligand-dependent heterodimerization of HER2 with other members of the HER family, blocking major signaling pathways and resulting in arrested cell growth and apoptosis.

On the basis of the APHINITY trial, the combination of pertuzumab, trastuzumab, and chemotherapy was granted approval in 2017 for the treatment of patients with HER2-positive early breast cancer at a high risk for recurrence.

Multiple biosimilars of trastuzumab are now FDA and EMA approved on the basis of their high similarity to the reference trastuzumab, and recently, researchers reported the results of a study that assessed one of those biosimilars, Samsung Bioepis’ Ontruzant, in combination with a subdomain II—targeting agent.¹

The study was a similarity assessment of in vitro antitumor activity between the biosimilar and the reference, and it was performed on HER2-overexpressing breast cancer and gastric cancer cells through an analysis of HER2 dimerization, cell proliferation, survival activities, and antibody-dependent cellular cytotoxicity in the presence of a subdomain II—targeting antibody.

The investigators found that the biosimilar and the reference in combination with a subdomain II—targeting antibody had similar in vitro inhibition rates for HER2 and HER3 heterodimerization.

The cancer cells’ growth inhibition rate was similar, whether the biosimilar or the reference was used in combination with the second agent. Cell killing activity, assessed by an antibody-dependent cellular cytotoxicity assay in the presence of the subdomain II—targeting antibody, was shown with both the reference and the biosimilar trastuzumab.

The researchers concluded that the biosimilar and the reference show high similarity in their in vitro antitumor activity when combined with a subdomain II—targeting antibody.

Reference

1. Lee JH, Paek K, Kim E, Kim I, Jeong J, Kim S. Comparison of in vitro antitumor activity between SB3 (trastuzumab biosimilar, Ontruzant) and Herceptin combined with an antibody for subdomain II of HER2 in HER2-positive cancer cells. Presented at: Presented at: the American Society of Clinical Oncology Annual Meeting 2019; May 31-June 4, 2019; Chicago, Illinois. Abstract e14001.