Antibody-Drug Conjugates in Colorectal Cancer: A Scoping Review of Current Evidence and Emerging Clinical Trends
Author(s)
Nallamothu Bhargavi, Ph.D.1, Kapil Maheshchandra KHAMBHOLJA, Ph.D.2, VATSAL AKHILESH CHHAYA, Ph.D.2, Padma Ramasamy, PhD1.
1Medical Writing, Catalyst Clinical Research, Trivandrum, India, 2Medical Writing, Catalyst Clinical Research, Vadodara, India.
1Medical Writing, Catalyst Clinical Research, Trivandrum, India, 2Medical Writing, Catalyst Clinical Research, Vadodara, India.
OBJECTIVES:
Colorectal cancer (CRC) has few targeted treatments beyond anti-EGFR and anti-VEGF therapies. Antibody-drug conjugates (ADCs) provide a targeted approach with potential for improved efficacy and reduced toxicity. However, existing evidence on ADCs in CRC is scattered and not comprehensively reviewed. This scoping review aims to map current data and identify knowledge gaps.
METHODS:
We conducted a scoping review following PRISMA-ScR guidelines to assess the evidence on ADCs in CRC. A comprehensive search of peer-reviewed and grey literature (2015-2025) was performed across PubMed, Embase, and ClinicalTrials.gov. Eligible studies included clinical trials and real-world data involving CRC patients (any stage) treated with ADCs. Extracted data included molecular targets, efficacy (ORR, PFS, OS), safety, and trial design.
RESULTS:
Eighteen studies met inclusion criteria: 12 phase I/II trials, 3 observational studies, and 3 conference abstracts. Most were early-phase, single-arm trials in heavily pretreated metastatic CRC patients (median 2-4 prior therapies). Targets evaluated included HER2, TROP-2, CEACAM5, and C-Met. ADCs such as trastuzumab deruxtecan (HER2), sacituzumab govitecan (TROP-2), and labetuzumab govitecan (CEACAM5) showed ORRs of 7%-45% and PFS of 2-6 months. Common adverse events included neutropenia, diarrhea, and fatigue, with some dose-limiting toxicities leading to treatment discontinuation. Results indicate variable but promising activity in biomarker-defined CRC subgroups.
CONCLUSIONS:
Early-phase studies suggest modest clinical benefit of ADCs in heavily pretreated CRC, particularly in HER2-, TROP-2-, and CEACAM5-positive cases. The data underscore the need for better biomarker-driven selection, rational combinations, and earlier-line evaluation to define their role in CRC management.
Colorectal cancer (CRC) has few targeted treatments beyond anti-EGFR and anti-VEGF therapies. Antibody-drug conjugates (ADCs) provide a targeted approach with potential for improved efficacy and reduced toxicity. However, existing evidence on ADCs in CRC is scattered and not comprehensively reviewed. This scoping review aims to map current data and identify knowledge gaps.
METHODS:
We conducted a scoping review following PRISMA-ScR guidelines to assess the evidence on ADCs in CRC. A comprehensive search of peer-reviewed and grey literature (2015-2025) was performed across PubMed, Embase, and ClinicalTrials.gov. Eligible studies included clinical trials and real-world data involving CRC patients (any stage) treated with ADCs. Extracted data included molecular targets, efficacy (ORR, PFS, OS), safety, and trial design.
RESULTS:
Eighteen studies met inclusion criteria: 12 phase I/II trials, 3 observational studies, and 3 conference abstracts. Most were early-phase, single-arm trials in heavily pretreated metastatic CRC patients (median 2-4 prior therapies). Targets evaluated included HER2, TROP-2, CEACAM5, and C-Met. ADCs such as trastuzumab deruxtecan (HER2), sacituzumab govitecan (TROP-2), and labetuzumab govitecan (CEACAM5) showed ORRs of 7%-45% and PFS of 2-6 months. Common adverse events included neutropenia, diarrhea, and fatigue, with some dose-limiting toxicities leading to treatment discontinuation. Results indicate variable but promising activity in biomarker-defined CRC subgroups.
CONCLUSIONS:
Early-phase studies suggest modest clinical benefit of ADCs in heavily pretreated CRC, particularly in HER2-, TROP-2-, and CEACAM5-positive cases. The data underscore the need for better biomarker-driven selection, rational combinations, and earlier-line evaluation to define their role in CRC management.
Conference/Value in Health Info
2025-11, ISPOR Europe 2025, Glasgow, Scotland
Value in Health, Volume 28, Issue S2
Code
CO11
Topic
Clinical Outcomes
Topic Subcategory
Clinical Outcomes Assessment
Disease
Oncology