Post-Marketing Surveillance Data Reinforce Trastuzumab Biosimilar Safety in HER2+ Gastric Cancer

Data from a post-marketing surveillance study of the trastuzumab biosimilar CT-P6 (trastuzumab-pkrb, Herzuma) in Japan showed a disease control rate of 82%, progression-free survival of 7.4 months, and “no new safety concerns” in HER2-positive (HER2+) advanced gastric cancer. According to the authors, this post-marketing surveillance study is the first prospective cohort study evaluating real-world safety and effectiveness of CT-P6 in HER2+ advanced gastric cancer.

Trastuzumab, a monoclonal antibody targeting the human epidermal growth factor receptor-2 (HER2), inhibits proliferation of tumor cells overexpressing HER2, and is used to treat HER2+ breast cancer and metastatic gastric cancers. The reference product (Herceptin) was first approved by the US FDA in 1998. The authors noted that therapies targeting HER2 have “markedly improved” clinical outcomes for patients with HER2+ cancers. The biosimilar CT-P6 was approved in the European Union, US, and Japan in 2018 for all indications of the reference product, based on extrapolation from a clinical trial on HER2-positive breast cancer, “highlighting the need for gastric cancer-specific evidence,” according to the authors. In Japan, the post-market surveillance study was required by the Ministry of Health, Labour, and Welfare (MHLW) as a condition for the approval of the biosimilar.

A total of 171 patients with HER2-positive unresectable advanced or recurrent gastric cancer were enrolled in the post-marketing surveillance study. CT-P6 was combined with chemotherapy, primarily fluoropyrimidine and platinum agents. In the majority of patients (59%), CT-P6 with chemotherapy was used as first-line therapy for inoperable tumors.

Adverse events (AEs) occurred in 151 patients (88%), 55 of whom (32%) experienced grade 3 or higher AEs. Infusion reactions occurred in 12% of patients, all of which were related to CT-P6, and none were serious. AEs related to CT-P6 occurred in 67% of patients. AEs occurring in more than 20% of patients included anemia, neutropenia, thrombocytopenia, diarrhea, nausea, anorexia, and peripheral neuropathy, most of which (90%) were related to CT-P6. Cardiac AEs and interstitial lung disease occurred in 4 patients each (2%), and were related to CT-P6.The authors commented that the safety profile of CT-P6 in this study was “consistent with that observed in the clinical trials.”

The objective response rate was 34%, the disease control rate was 82%, and three patients (2%) achieved a complete response. Regression analysis on data from 156 patients treated with CT-P6 in combination with fluoropyrimidine showed several prognostic factors that were significantly associated with shorter progression-free survival, including primary tumor site at the gastroesophageal junction, three or more metastases, no gastrectomy, prior chemotherapy, and no use of platinum agents.

During the one-year observation period, 123 patients (73%) discontinued treatment, 89 (53%) due to disease progression, and 16 patients (9.5%) due to AEs. Thirty patients (18%) continued CT-P6 therapy for the entire year, seven (4%) completed the planned treatment, and eight (5%) underwent conversion surgery following a good tumor response to CT-P6 therapy. The authors concluded that CT-P6 showed “sufficient efficacy and no new safety concerns” in HER2-positive advanced gastric cancer.

Reference

Taniguchi H, Nishikawa K, Haneji T, Izawa N, Imamura H, Yamaguchi H. Prospective cohort study of trastuzumab biosimilar CT-P6 in HER2-positive gastric cancer: Japanese real-world outcomes. Oncol Ther. 2025;13(2):485-503. doi:10.1007/s40487-025-00341-7