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Advances in Systemic Therapy for Metastatic or Advanced Gastric Cancer
Kohei Shitara1, Atsushi Ohtsu1
1From the Department of Gastrointestinal Oncology, National Cancer Center Hospital East, Kashiwa, Chiba, Japan.
Abstract:
In recent years, various new agents have been investigated for the treatment of advanced gastric cancer (AGC). The anti-HER2 antibody trastuzumab has been shown to prolong the overall survival of patients with HER2-positive AGC and has become a standard treatment. However, lapatinib, or ado-trastuzumab emtansine (T-DM1), did not show survival benefit in AGC, although it has shown remarkable efficacy for HER2-positive breast cancer. The efficacy of the anti-vascular endothelial growth factor receptor monoclonal antibody ramucirumab for pretreated gastric cancer is a milestone for antiangiogenic therapy for AGC. Early clinical trials of TAS-118, TAS-102, and STAT3 inhibitors; IMAB362 (anti-Claudin 18.2); and immune checkpoint inhibitors are all encouraging. These findings warrant further evaluation in larger clinical trials.
Insights
New agents show promise for advanced gastric cancer (AGC) treatment. While trastuzumab is standard for HER2-positive AGC, other targeted therapies and immunotherapies are emerging as potential breakthroughs.
Area of Science:
- Oncology
- Gastroenterology
- Pharmacology
Background:
- Advanced gastric cancer (AGC) treatment has seen evolving therapeutic strategies.
- Trastuzumab is a standard therapy for HER2-positive AGC, improving overall survival.
- Previous targeted therapies like lapatinib and T-DM1 have shown limited efficacy in AGC.
Purpose of the Study:
- To review recent advancements in novel therapeutic agents for advanced gastric cancer.
- To evaluate the efficacy of emerging treatments beyond HER2-targeted therapy.
- To highlight promising agents for future clinical trials in AGC management.
Main Methods:
- Review of recent clinical trial data and scientific literature.
- Analysis of efficacy and survival data for various novel agents in AGC.
- Focus on targeted therapies, antiangiogenic agents, and immunotherapies.
Main Results:
- Ramucirumab demonstrated efficacy in pretreated gastric cancer, marking a milestone for antiangiogenic therapy.
- Early trials of TAS-118, TAS-102, STAT3 inhibitors, IMAB362 (anti-Claudin 18.2), and immune checkpoint inhibitors are encouraging.
- Trastuzumab remains a standard for HER2-positive AGC, but other agents show potential for broader application.
Conclusions:
- Several novel agents, including antiangiogenic and immunotherapeutic drugs, show promise for advanced gastric cancer.
- Further large-scale clinical trials are warranted to confirm the efficacy and safety of these emerging treatments.
- The landscape of AGC treatment is expanding with new targeted and immune-based therapeutic options.
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