Trastuzumab Deruxtecan: Changing the Destiny of HER2 Expressing Solid Tumors

Area of Science:

• Oncology
• Pharmacology
• Drug Development

Background:

• HER2-targeted therapies have transformed outcomes for HER2-positive breast and gastric cancers.
• HER2 overexpression/mutation drives non-small cell lung cancer (NSCLC) and colorectal cancer, yet lacks approved targeted therapies.
• Trastuzumab deruxtecan (T-DXd) is an antibody-drug conjugate demonstrating efficacy in pre-treated HER2-positive cancers.

Purpose of the Study:

• To review the pharmacologic characteristics and toxicity of Trastuzumab deruxtecan (T-DXd).
• To update on recent clinical trial results for T-DXd in solid tumors, including NSCLC and colorectal cancer.
• To overview ongoing combination therapy research for T-DXd in solid tumors.

Main Methods:

• Literature search of PubMed using terms: T-DXd, breast cancer, gastric cancer, NSCLC, colorectal cancer (search date: March 16, 2021).
• Inclusion of data from ASCO 2020 and ESMO 2020 presentations (oral, abstract, poster).
• Search of ClinicalTrials.gov for ongoing T-DXd trials in solid tumors.

Main Results:

• Trastuzumab deruxtecan (T-DXd) exhibits significant anti-tumor activity in heavily pre-treated HER2-positive breast and gastric cancers.
• Preliminary data indicate promising objective response rates for T-DXd in HER2-positive NSCLC and colorectal cancer.
• T-DXd demonstrates an acceptable safety profile, though serious treatment-emergent adverse events are a concern.

Conclusions:

• Trastuzumab deruxtecan (T-DXd) represents a promising therapeutic option for HER2-positive NSCLC and colorectal cancer.
• Further investigation into T-DXd's efficacy, safety, and combination strategies is warranted.
• Ongoing trials will shape future treatment paradigms for solid tumors with HER2 alterations.