Treating HER2-Positive Gastric Cancer with Trastuzumab Deruxtecan
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Reviewed & Translated by Dat Tien Nguyen, B.A, ScM.
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Posted on August 13th, 2025
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Gastric cancer is one of the most prevalent cancers in Vietnam, and it is associated with significant quality of life deterioration. Previous studies had found that between 5% and 17% of gastric cancer tumors express human epidermal growth factor receptor 2 (HER2). The pharmaceutical companies Daiichi Sankyo and AstraZeneca had co-funded a study to take advantage of this new therapeutic target - using trastuzumab deruxtecan to treat gastric cancer.
The phase 2 clinical study included 494 participants who had been diagnosed with unresectable or metastatic cancer. 60% of the participants have their tumor located in the stomach, and the remaining located in the gastroesophageal junction. Tumor analysis was performed to ensure that all of the patients were HER2 positive, with around 84% of the participants having an immunohistochemical score of IHC 3+.
The patients were randomly assigned to be treated intravenously with either the standard combination therapy or the experimental trastuzumab deruxtecan. The combination therapy included ramucirumab, an antibody that slows down angiogenesis by targeting vascular endothelial growth factor receptors, and paclitaxel, an anti-tubulin agent that interferes with cell division. The experimental agent, trastuzumab deruxtecan is a conjugated compound with parts. It is composed of an antibody targeting HER-2, which guides the active subunit - an agent that neutralizes nucleic acid replication by inhibiting unwinding by topoisomerase - to the HER2-positive tumor.
After more than 33 months, the researchers found that trastuzumab deruxtecan reduce the risk of death and disease progression by around 25%. More of the patients treated with trastuzumab deruxtecan experience tumor shrinkage than those treated with the ramucirumab-paclitaxel combination. Side effects were similar between the two groups, with patients treated with trastuzumab deruxtecan reported a higher frequency of nausea, vomiting, elevated liver enzyme, leukopenia, and thrombocytopenia. The authors noted that previous study had found trastuzumab deruxtecan increase the risk of interstitial lung diseases and pneumonitis, which is captured in the result of this study.
The phase 2 clinical study included 494 participants who had been diagnosed with unresectable or metastatic cancer. 60% of the participants have their tumor located in the stomach, and the remaining located in the gastroesophageal junction. Tumor analysis was performed to ensure that all of the patients were HER2 positive, with around 84% of the participants having an immunohistochemical score of IHC 3+.
The patients were randomly assigned to be treated intravenously with either the standard combination therapy or the experimental trastuzumab deruxtecan. The combination therapy included ramucirumab, an antibody that slows down angiogenesis by targeting vascular endothelial growth factor receptors, and paclitaxel, an anti-tubulin agent that interferes with cell division. The experimental agent, trastuzumab deruxtecan is a conjugated compound with parts. It is composed of an antibody targeting HER-2, which guides the active subunit - an agent that neutralizes nucleic acid replication by inhibiting unwinding by topoisomerase - to the HER2-positive tumor.
After more than 33 months, the researchers found that trastuzumab deruxtecan reduce the risk of death and disease progression by around 25%. More of the patients treated with trastuzumab deruxtecan experience tumor shrinkage than those treated with the ramucirumab-paclitaxel combination. Side effects were similar between the two groups, with patients treated with trastuzumab deruxtecan reported a higher frequency of nausea, vomiting, elevated liver enzyme, leukopenia, and thrombocytopenia. The authors noted that previous study had found trastuzumab deruxtecan increase the risk of interstitial lung diseases and pneumonitis, which is captured in the result of this study.