Predicting Therapeutic Response to Antibody-Drug Conjugates Using Targeted PET Imaging: A Systematic Review

Area of Science:

• Oncology
• Radiology
• Pharmacology

Background:

• Antibody-drug conjugates (ADCs) show expanding clinical utility but have heterogeneous treatment responses.
• Predictive biomarkers for ADC therapy are limited.
• Positron emission tomography (PET) imaging can non-invasively assess whole-body target antigen availability, crucial for ADC efficacy.

Purpose of the Study:

• To systematically review the literature evaluating the relationship between PET-measured tumor antigen expression and therapeutic response to ADCs targeting the same antigen.

Main Methods:

• A systematic literature search was conducted using PubMed, EMBASE, and Web of Science databases.
• PRISMA guidelines were followed for study selection and data extraction.
• Two independent reviewers screened articles, with disagreements resolved by consensus.

Main Results:

• Seven trials were included, investigating ADCs targeting HER2, Nectin-4, mesothelin, and STEAP1.
• Higher PET uptake of target antigens correlated with a greater likelihood of treatment response in HER2- and Nectin-4-targeted trials.
• Included trials were generally small with a moderate risk of bias.

Conclusions:

• Targeted PET imaging demonstrates potential as a predictive biomarker for ADC treatment response.
• Further clinical trials with standardized protocols and harmonized designs are necessary for clinical integration.