Trastuzumab biosimilar on par with reference agent in HER2-positive gastric cancer

CT-P6, a trastuzumab biosimilar approved for the treatment of human epidermal growth factor receptor 2 (HER2)-positive advanced gastric cancer (AGC), is as efficacious as reference trastuzumab in terms of response rates, progression-free (PFS) and overall survival (OS), a study has shown.

“Biosimilar trastuzumab can suitably and safely replace trastuzumab as a reference for the treatment of HER2-positive AGC,” the researchers said.

The medical records of 102 patients with HER2-positive AGC treated with first-line trastuzumab-based chemotherapy were reviewed retrospectively. Patients received either reference (n=72) or biosimilar (n=30) trastuzumab. The researchers then compared treatment outcomes between the two groups.

The objective response rate was comparable between the reference and biosimilar groups (52.8 percent vs 56.8 percent; p=0.72). [Am J Clin Oncol 2022;45:61-65]

No statistically significant between-group differences were also noted for PFS (median 6.9 vs 5.4 months; p=0.98) or OS (median 12.3 months vs not reached; p=0.42). Likewise, safety profiles were similar between reference and biosimilar trastuzumab.

“[T]argeted cancer drugs such as trastuzumab are relatively more expensive compared with other chemotherapy drugs. Despite its clinical benefits, this high price can represent a substantial barrier to trastuzumab treatment, especially in a financially constrained environment,” the researchers said. [Pharmaceuticals (Basel) 2014;7:943-953]

“Since the price of biosimilars is generally lower than that of the reference products, the cost saved by switching patients to biosimilars could enable improved access to these clinically effective drugs,” they added.

So far, five trastuzumab biosimilars have been approved by the US Food and Drug Administration: trastuzumab-anns, trastuzumab-dkst, trastuzumab-dttb, trastuzumab-pkrb, and trastuzumab-qyyp. [www.fda.gov/drugs/biosimilars/biosimilar-product-information]

CT-P6 or trastuzumab-pkrb, produced by the South Korean biotechnology company Celltrion, has exhibited similar pharmacodynamics and efficacy to reference trastuzumab in several clinical trials. [Cancer Chemother Pharmacol 2019;84:839-847; J Clin Oncol 2013;31(suppl):629; Breast 2017;32:S68-S69; Lancet Oncol 2017;18:917-928]

“Trastuzumab biosimilars have been studied only in patients with breast cancer, and extrapolation has been granted from early breast cancer to metastatic breast cancer and metastatic gastric cancer,” the researchers said.

“Extrapolation is an established regulatory principle that refers to the approval of a biosimilar for use in an indication held by the reference product, not directly studied in a comparative clinical trial with a biosimilar,” they added. [www.fda.gov/drugs/biosimilars/biosimilar-development-review-and-approval]

In addition, a recent study has demonstrated the efficacy of CT-P6 in patients with HER2-positive AGC when used in combination with pembrolizumab and chemotherapy. [J Clin Oncol 2020;38(suppl):3081]

The present study was limited by its retrospective nature, small sample size, and inconsistent follow-up echocardiography following trastuzumab treatment. Echocardiography was conducted to assess cardiac function when heart failure (HF) was suspected. Patients with no HF symptoms but had decreased cardiac function might have been missed.

“The results of [the current] study will help investigators in planning clinical studies in patients treated with biosimilar trastuzumab,” the researchers said. “Further prospective studies with large numbers of patients are, however, needed to validate these results.”