Trastuzumab deruxtecan for the treatment of HER2-positive advanced gastric cancer: a clinical perspective.
Masahiko AokiSatoru IwasaNarikazu BokuPublished in: Gastric cancer : official journal of the International Gastric Cancer Association and the Japanese Gastric Cancer Association (2021)
Human epidermal growth factor receptor 2 (HER2)-positive gastric cancer is a subtype for which new drugs and specific treatment strategies should be developed. Trastuzumab deruxtecan (T-DXd) is a novel HER2-targeted antibody-drug conjugate containing topoisomerase I inhibitor as a payload. In the randomized phase 2 study (DESTINY-Gastric01) for HER2-positive advanced gastric or gastroesophageal junction cancer (AGC), patients treated with T-DXd showed a significantly higher response rate compared with the chemotherapy of physician's choice, associated with remarkably prolonged progression-free and overall survival. T-DXd also exhibits anti-tumor activity to HER2-negative tumor cells close to HER2-positive cells (so-called bystander killing effect). T-DXd was effective even for HER2-low expressing breast and gastric cancer in several clinical studies. Taking advantage of these strong points and synergism with other cytotoxic, molecular-targeted and immunological agents, it is expected that T-DXd will bring further progression in treatment both for strongly and weakly HER2 positive AGC in various treatment settings including perioperative chemotherapy.
Keyphrases
- epidermal growth factor receptor
- open label
- emergency department
- endothelial cells
- induced apoptosis
- tyrosine kinase
- patients undergoing
- randomized controlled trial
- double blind
- clinical trial
- lymph node
- signaling pathway
- cell death
- placebo controlled
- drug delivery
- cell proliferation
- endoplasmic reticulum stress
- drug induced
- metastatic breast cancer
- phase iii
- pi k akt
- anti inflammatory
- decision making
- free survival
- cell cycle arrest