Overview of Trastuzumab Biosimilars in HER2-Positive Breast Cancer

Authors of a systematic review summarized the results of 21 published studies on the efficacy, safety, and cost-benefit ratio of trastuzumab biosimilars in human epidermal growth factor receptor 2 (HER2)-positive breast cancer.

Authors of a systematic review summarized the results of 21 published studies on the efficacy, safety, and cost-benefit ratio of trastuzumab biosimilars in human epidermal growth factor receptor 2 (HER2)-positive breast cancer.

The HER2 Receptor and Trastuzumab Use in HER2-positive Breast Cancer

HER2 is a cell surface receptor activated by epidermal growth factor that upon activation, promotes cell growth and proliferation. HER2 is overexpressed in about 20% to 25% of breast cancer cases, the reviewers said, and HER2 overexpression is associated with more aggressive disease, higher recurrence rate, and poorer disease-free and overall survival compared to HER2-negative breast cancers.

Trastuzumab is a monoclonal antibody targeting the HER2 receptor and is used to treat HER2-positive breast cancers and metastatic gastric cancers. It inhibits the proliferation of cells overexpressing HER2 and also recruits immune cells to tumor regions with overexpression of HER2. Trastuzumab has been in use since its approval by the FDA in 1998 and European Medicines Agency (EMA) in 2000, and “as with most biologics, trastuzumab has a high price compared to traditional cytotoxic chemotherapy,” the reviewers wrote.

Trastuzumab Biosimilars

According to the authors, there are 5 trastuzumab biosimilars currently available in the US, which were approved starting in 2017. At least 9 additional biosimilars are currently being developed, mostly in phase 1 studies. The 5 currently available are SB3 (Ontruzant), CT-P6 (trastuzumab-pkrb, Herzuma), ABP 980 (Kanjinti), PF-05280014 (Trazimera), and trastuzumab-dkst (Ogivri).

No Significant Differences in Efficacy and Safety Compared to the Reference Product in Clinical Studies

The authors reviewed clinical efficacy and safety studies on trastuzumab biosimilars in HER2-positive breast cancer, both available biosimilars and those still in development. Of the 21 studies, 3 were phase 3 studies on biosimilars still in development.

They noted that the sample sizes and methodology in these studies were “satisfactory,” and that the majority of studies were carried out in China, the Republic of Korea, and India. The most common primary endpoint in these studies was complete response rate; additional endpoints included disease-free survival, overall survival, and time to cessation of treatment.

Summarizing the efficacy results of the studies, the reviewers wrote, “there were no statistically significant differences between the above-mentioned parameters, thus confirming the assumption that biosimilars are not inferior to the reference product.”

The authors also reported there were “no obvious differences in clinical safety” between trastuzumab biosimilars and the originator, as the types and frequency of both serious and mild side effects were not different between reference product and biosimilar study arms. Furthermore, the incidence of anti-drug antibodies was not higher in biosimilar groups compared to reference product groups.

Cost Savings Associated With Trastuzumab Biosimilars

The authors cited 2 studies that estimated potential cost savings associated with using trastuzumab biosimilars in place of the reference product in Europe. One study that modeled cost savings across 28 countries in Europe, with a rate of transition from originator to biosimilars of 20% the first year followed by 5% each subsequent year estimated savings of €0.91-2.27 billion over 5 years. They added that this cost savings could allow 55,000 to 116,000 additional patients to be treated with trastuzumab biosimilars. They suggested that future cost-effectiveness analyses will be important to “raise the awareness of healthcare providers about these emerging and cost-effective treatments.”

The Future of Trastuzumab in HER2-positive Breast Cancer

Finally, the reviewers described in vitro-transcribed messenger RNA (IVT-mRNA), a technological advance which may be important for future treatment of breast cancer. Although the technique has only been studied in animal models so far, they commented that endogenous production of antibodies via IVT-mRNA “eliminates many of the previously described difficulties of antibody production.”

The authors concluded that trastuzumab biosimilars, both those approved and those still being investigated, have demonstrated similar efficacy and safety to the originator. Since the originator is available for both intravenous and subcutaneous administration but trastuzumab biosimilars are only available for the intravenous route, the development of trastuzumab biosimilars for subcutaneous administration “will be a step forward in the treatment of patients, as a large number of them are expected to choose this route of administration.” The potential approval of new trastuzumab biosimilars in the pipeline “is expected to save hundreds of thousands of lives worldwide each year, as an increasing number of patients will be able to access these modern treatments.”


Triantafyllidi E, Triantafillidis JK. Systematic Review on the Use of Biosimilars of Trastuzumab in HER2+ Breast Cancer. Biomedicines. 2022;10(8):2045. doi: 10.3390/biomedicines10082045