A trastuzumab biosimilar was found to have similar safety and efficacy with the reference product (Herceptin) in patients with advanced gastric cancer, a population previously excluded from bioequivalence studies for trastuzumab biosimilars.
A retrospective study has demonstrated equivalent safety and efficacy between Celltrion Healthcare’s trastuzumab biosimilar CT-P6 (Herzuma, trastuzumab-pkrb) and Herceptin (reference trastuzumab) in patients with advanced gastric cancer (AGC).
Published in American Journal of Clinical Oncology, the study from the Republic of Korea is the first to directly compare the efficacy and safety of a trastuzumab biosimilar with the reference product in patients with AGC.
Herzuma has been approved for use in the Republic of Korea, the United States, and the European Union for the treatment of human epidermal growth factor receptor 2 (HER2)-positive breast and gastric cancers. Prior to the present analysis, studies assessing the biosimilarity of trastuzumab biosimilars with Herceptin had only focused on patients with breast cancer.
The United States currently has 5 FDA-approved trastuzumab biosimilars and the European Union has 6 approved by the European Medicines Agency. Extrapolation has allowed for these biosimilars to have indications for gastric cancers despite them not having been tested in these patients.
In 2020, there were more than 1 million new cases of gastric cancer, which is often diagnosed at an advanced stage. In addition, HER2 is overexpressed or amplified in 20% to 25% of gastric and gastroesophageal junction cancers. Cytotoxic chemotherapy is considered the standard of care for palliative treatment, and trastuzumab combined with platinum-based chemotherapy is considered frontline therapy for HER2-positive AGC.
The investigators examined 102 patients 18 years or older with HER2 overexpression or HER2-amplified AGC who received first-line trastuzumab-based chemotherapy between February 2011 and December 2020 at the Gachon University Gil Medical Center in the Republic of Korea. The patients could not have received chemotherapy, except for adjuvant chemotherapy completed at least 6 months prior to study enrollment.
In total, 72 patients were given the reference product and 30 patients were administered the biosimilar. Trastuzumab was administered intravenously at an 8-mg/kg dose on day 1 of the first chemotherapy cycle, followed by 6-mg/kg doses every 3 weeks for up to 8 cycles. The median number of chemotherapy cycles was similar between the groups.
The mean age of the patients was 63 years for the reference group and 66 years for the biosimilar group. Men accounted for 81.9% and 96.7%, respectively.
Two patients in the reference group and none in the biosimilar group achieved a complete response. The overall response rate of the groups was not significantly different, at 52.8% in the reference group vs 56.7% in the biosimilar group (P = .720). The disease control rates were 69.4% and 73.3% (P = .695), respectively.
The median follow-up times for progression-free survival were 48.0 months and 7.2 months in the reference and biosimilar groups, respectively. Overall, 81 patients, 64 from the reference group and 17 from the biosimilar group, had their cancer progress or died during the follow-up period. The median overall survival was 12.3 months (95% CI, 9.3-21.7) in the reference group and was not reached (95% CI, 8.2-lower limit could not be calculated) in the biosimilar group (P = .42 for both). The outcomes were not statistically significantly different between the groups.
The proportion of the patients who reported at least 1 adverse event (AE) and grade 3 or worse treatment-related AEs was similar between both groups, with the most commonly reported AEs being related to hematological toxicities, including anemia, leukopenia, neutropenia, and thrombocytopenia.
Although heart failure was reported in 9 patients in the reference group and 3 patients in the biosimilar group, no grade 3 or 4 heart failure was reported. Among the entire cohort, only 27 (37.5%) patients in the reference group and 12 (40.0%) patients in the biosimilar group experienced a decrease in left ventricular ejection fraction.
The study had several limitations, including that the retrospective design meant that some AEs may have gone unreported. Additionally, the population was small, the study focused on a single center, and echocardiography was not routinely performed in patients during follow-up, suggesting that larger prospective studies are needed to confirm the present study’s findings and cardiovascular safety.
Park J-H, Yeo JH, Kim YS, et al. Efficacy and safety of trastuzumab biosimilar (CT-P6) compared with reference trastuzumab in patients with HER2-positive advanced gastric cancer. Am J Clin Oncol. 2022;45(2):61-65. doi:10.1097/COC.0000000000000887