Recent Progress in Treatment for HER2-Positive Advanced Gastric Cancer
Takeshi Kawakami1, Kentaro Yamazaki1
1Division of Gastrointestinal Oncology, Shizuoka Cancer Center, Shizuoka 411-0934, Japan.
Abstract:
Human epidermal receptor (HER) 2-positive advanced gastric cancer is one of the major subtypes of gastric cancer, accounting for ~20% of all cases. Although combination therapy with trastuzumab and chemotherapy provides meaningful survival benefit, clinical trials targeting HER2 have failed to demonstrate clinical benefits in first- or subsequent-line treatment. Trastuzumab deruxtecan, an antibody-drug conjugate, has shown positive results even in later-line treatment and has become new standard treatment. In first-line therapy, combination therapy with pembrolizumab and trastuzumab plus chemotherapy demonstrated a dramatic response rate. Therefore, the FDA rapidly approved it without waiting for the results of survival time. The emergence of combination therapy including immunotherapy with HER2-targeting agents and the development of HER2 targeting agents with or without immunotherapy have been advancing for treating HER2-positive gastric cancer. In this review, we will discuss the current status of treatment development and future perspectives for HER2-positive gastric cancer.
Insights
New treatments like trastuzumab deruxtecan and immunotherapy combinations show promise for HER2-positive gastric cancer, offering improved outcomes and new standards of care.
Area of Science:
- Oncology
- Gastroenterology
- Pharmacology
Background:
- Human epidermal receptor 2 (HER2)-positive advanced gastric cancer represents a significant subtype, impacting approximately 20% of patients.
- While trastuzumab combined with chemotherapy offers survival benefits, prior HER2-targeted therapies have shown limited success in early or later treatment lines.
- Trastuzumab deruxtecan, an antibody-drug conjugate, has emerged as a new standard, demonstrating efficacy in later-line treatments.
Purpose of the Study:
- To review the current treatment landscape for HER2-positive advanced gastric cancer.
- To discuss recent advancements in therapeutic strategies, including antibody-drug conjugates and immunotherapy combinations.
- To explore future directions and perspectives in managing this specific cancer subtype.
Main Methods:
- Review of clinical trial data and recent literature on HER2-positive gastric cancer treatments.
- Analysis of the efficacy and safety profiles of novel therapeutic agents and combinations.
- Discussion of emerging treatment paradigms, including immunotherapy and antibody-drug conjugates.
Main Results:
- Trastuzumab deruxtecan has established itself as a new standard of care, particularly in later-line treatment settings.
- Combination therapy with pembrolizumab, trastuzumab, and chemotherapy has shown a high response rate in first-line treatment, leading to rapid FDA approval.
- Advancements include the development of novel HER2-targeting agents and combination strategies incorporating immunotherapy.
Conclusions:
- The treatment of HER2-positive gastric cancer is rapidly evolving with the introduction of novel agents and combination therapies.
- Immunotherapy combined with HER2-targeted agents represents a promising frontier for improving patient outcomes.
- Continued research and development are crucial for optimizing treatment strategies and addressing unmet needs in HER2-positive gastric cancer.
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