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<p>HER2-targeted antibody-drug conjugates (ADCs) have achieved clinically meaningful activity in several human epidermal growth factor-2 (HER2)-positive malignancies. However, the efficacy of these agents in HER2-positive colorectal cancer (CRC) remains incompletely understood.To address this gap, we conducted a systematic review and meta-analysis to compare treatment outcomes of HER2-targeted ADC therapy in patients with HER2-positive CRC versus those with HER2-positive tumors of other origins. Five prospective clinical studies evaluating HER2-targeted ADCs in HER2-positive malignancies were included. Outcomes assessed included disease control rate (DCR), objective response rate (ORR), partial response (PR), stable disease (SD), and progressive disease (PD). Pooled odds ratios (ORs) with 95% confidence intervals (CIs) were calculated using fixed-effects models due to low heterogeneity. Four studies incorporating 45 patients with HER2-positive CRC and 107 patients with HER2-positive non-CRC tumors were included in the DCR analysis. No significant difference in DCR was observed between CRC and non-CRC cohorts (OR = 0.63, 95% CI: 0.25–1.57; <i>p</i> = 0.32), with minimal heterogeneity (Q(3) = 1.09, <i>p</i> = 0.78; I² = 0%). Five studies including 65 CRC patients and 189 non-CRC patients were analyzed for ORR. HER2-positive CRC patients exhibited a significantly lower ORR compared with patients with other HER2-positive malignancies (OR = 0.42, 95% CI: 0.20–0.88; <i>p</i> = 0.02), indicating that CRC patients were less than half as likely to achieve an objective response. Heterogeneity was negligible (Q(4) = 1.82, <i>p</i> = 0.77; I² = 0%). Four studies also assessed PR, SD, and PD. A trend toward reduced PR rates in CRC patients was observed but did not reach statistical significance (OR = 0.41, 95% CI: 0.16–1.07; <i>p</i> = 0.07; I² = 0%). Rates of SD were comparable between CRC and non-CRC cohorts (OR = 1.63, 95% CI: 0.74–3.61; <i>p</i> = 0.23; I² = 0%). Funnel plot analyses and statistical testing revealed no evidence of significant publication bias. While ADC therapy achieves disease control in HER2-positive CRC comparable to that in other HER2-positive malignancies, objective and partial response rates appear significantly lower. These findings suggest intrinsic differences in ADC sensitivity between CRC and other HER2-driven tumors and underscore the need for CRC-specific ADC development and biomarker-driven patient selection.</p>

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The therapeutic potential of antibody-drug conjugates in advanced colorectal cancer: a systematic review and meta-analysis

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年5月19日

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  • Daniel Sur,
  • Ionut-Constantin Coroama,
  • Alecsandra Gorzo,
  • Denise Smith,
  • Cristian Virgil Lungulescu,
  • Adina Turcu-Stiolica

摘要

HER2-targeted antibody-drug conjugates (ADCs) have achieved clinically meaningful activity in several human epidermal growth factor-2 (HER2)-positive malignancies. However, the efficacy of these agents in HER2-positive colorectal cancer (CRC) remains incompletely understood.To address this gap, we conducted a systematic review and meta-analysis to compare treatment outcomes of HER2-targeted ADC therapy in patients with HER2-positive CRC versus those with HER2-positive tumors of other origins. Five prospective clinical studies evaluating HER2-targeted ADCs in HER2-positive malignancies were included. Outcomes assessed included disease control rate (DCR), objective response rate (ORR), partial response (PR), stable disease (SD), and progressive disease (PD). Pooled odds ratios (ORs) with 95% confidence intervals (CIs) were calculated using fixed-effects models due to low heterogeneity. Four studies incorporating 45 patients with HER2-positive CRC and 107 patients with HER2-positive non-CRC tumors were included in the DCR analysis. No significant difference in DCR was observed between CRC and non-CRC cohorts (OR = 0.63, 95% CI: 0.25–1.57; p = 0.32), with minimal heterogeneity (Q(3) = 1.09, p = 0.78; I² = 0%). Five studies including 65 CRC patients and 189 non-CRC patients were analyzed for ORR. HER2-positive CRC patients exhibited a significantly lower ORR compared with patients with other HER2-positive malignancies (OR = 0.42, 95% CI: 0.20–0.88; p = 0.02), indicating that CRC patients were less than half as likely to achieve an objective response. Heterogeneity was negligible (Q(4) = 1.82, p = 0.77; I² = 0%). Four studies also assessed PR, SD, and PD. A trend toward reduced PR rates in CRC patients was observed but did not reach statistical significance (OR = 0.41, 95% CI: 0.16–1.07; p = 0.07; I² = 0%). Rates of SD were comparable between CRC and non-CRC cohorts (OR = 1.63, 95% CI: 0.74–3.61; p = 0.23; I² = 0%). Funnel plot analyses and statistical testing revealed no evidence of significant publication bias. While ADC therapy achieves disease control in HER2-positive CRC comparable to that in other HER2-positive malignancies, objective and partial response rates appear significantly lower. These findings suggest intrinsic differences in ADC sensitivity between CRC and other HER2-driven tumors and underscore the need for CRC-specific ADC development and biomarker-driven patient selection.