Trastuzumab deruxtecan: Redefining precision oncology across HER2-driven cancers

Area of Science:

• Oncology
• Pharmacology
• Biotechnology

Background:

• Trastuzumab deruxtecan (T-DXd) is an antibody-drug conjugate (ADC) targeting HER2-expressing cancers.
• It features a potent topoisomerase I inhibitor linked to an anti-HER2 antibody, enabling a bystander effect.
• T-DXd demonstrates efficacy in tumors with varying HER2 expression levels.

Purpose of the Study:

• To review the mechanism of action of T-DXd.
• To summarize pivotal clinical evidence supporting its use.
• To outline emerging applications and future prospects of T-DXd in oncology.

Main Methods:

• Review of clinical trial data and scientific literature.
• Analysis of T-DXd's mechanism of action, including its drug-to-antibody ratio and bystander effect.
• Evaluation of T-DXd's efficacy across multiple cancer types.

Main Results:

• T-DXd shows significant improvements in progression-free and overall survival in HER2-positive breast cancer compared to T-DM1.
• It is the first ADC approved for HER2-positive gastric cancer and shows activity in HER2-low subgroups.
• Clinically meaningful responses observed in HER2-mutant NSCLC and HER2-positive colorectal cancer, highlighting its role as a precision medicine.

Conclusions:

• Trastuzumab deruxtecan represents a transformative therapy for HER2-driven cancers.
• Its efficacy extends beyond HER2 amplification, including HER2-low and HER2-mutant settings.
• Future directions include combination strategies, biomarker selection, and expanded global access.