Efficacy and safety of antibody-drug conjugates in advanced colorectal cancer: A systematic review and single-arm meta-analysis of early-phase clinical trials.

Abstract

e15616 Background: Colorectal cancer (CRC) remains the second leading cause of cancer-related mortality worldwide. Despite standard-of-care systemic therapy for metastatic CRC (mCRC), most patients experience disease progression with limited subsequent treatment options. Antibody-drug conjugates (ADCs) deliver cytotoxic payloads directly to tumor cells via tumor-specific monoclonal antibodies and represent a promising therapeutic class. While multiple ADCs are approved for other solid tumors, disease-specific ADC options for CRC remain an unmet need. This meta-analysis evaluates the efficacy and safety of ADCs in advanced CRC. Methods: We systematically searched PubMed, Embase, Cochrane CENTRAL, and ClinicalTrials.gov through December 2025 for clinical trials evaluating ADCs in advanced/metastatic CRC. Primary outcomes included median progression-free survival (mPFS) and median overall survival (mOS). Safety outcomes included any grade and grade ≥3 treatment-related adverse events (TRAEs). Pooled estimates were calculated using random-effects models with 95% confidence intervals (CIs). Statistical analyses were performed using R software. Results: Four early-phase clinical trials comprising 289 patients were included. ADCs evaluated included indusatumab vedotin, labetuzumab govitecan, trastuzumab deruxtecan, and precemtabart tocentecan. Median treatment duration ranged from 6 to 24 weeks across studies. Pooled analysis demonstrated a mPFS of 4.39 months (95% CI: 2.67-6.12; I² = 93.9%, p < 0.0001). Among 168 patients with available OS data, mOS was 10.1 months (95% CI: 3.7-16.4; I² = 96.5%, p < 0.0001). Safety analysis of 203 patients revealed any-grade TRAEs in 99.8% (95% CI: 98.1-100) and grade ≥3 TRAEs in 55.2% (95% CI: 41.6-68.5; I² = 74%, p = 0.009). Conclusions: ADCs demonstrate modest antitumor activity in heavily pretreated advanced CRC with manageable but notable toxicity. The mPFS of 4.39 months and mOS of 10.1 months suggest potential clinical benefit in this population with limited therapeutic options. However, the high incidence of any-grade TRAEs (99.8%) and grade ≥3 TRAEs (55.2%) warrants careful patient selection and monitoring. Significant heterogeneity indicates efficacy varies by ADC platform. Patient selection strategies and randomized controlled trials are warranted to definitively establish the role of ADCs in CRC.