Neoadjuvant antibody–drug conjugate regimens without concurrent chemotherapy versus standard chemotherapy in early HER2-positive breast cancer: A systematic review and meta-analysis of randomized trials.

e12644 Background: Standard neoadjuvant therapy for HER2-positive early breast cancer combines multi-agent chemotherapy with HER2-targeted antibodies and is associated with substantial toxicity. HER2-directed antibody–drug conjugates (ADCs) may enable de-escalation. We compared efficacy and toxicity of neoadjuvant ADC-based regimens given without concurrent chemotherapy versus standard chemotherapy-based regimens, including by platinum use in the control arm. Methods: We searched PubMed, Embase, Cochrane CENTRAL, Scopus, and Web of Science through December 18, 2024 for randomized controlled trials in early/locally advanced HER2-positive breast cancer. Eligible trials compared neoadjuvant ADC-based regimens without concurrent chemotherapy versus standard chemotherapy-based regimens. Outcomes were pathologic complete response (pCR; per trial definition), grade ≥3 adverse events (AEs), and treatment discontinuation. Odds ratios (ORs) were pooled and heterogeneity was summarized with I². Results: Nine randomized trials (n = 2,021; mean age 50.7±13.7) were included. There was no significant difference in pCR between groups (OR 0.93, 95% CI 0.62–1.40; I² = 59.8%). ADC-based regimens were associated with fewer grade ≥3 AEs (OR 0.30, 95% CI 0.11–0.84; I² = 91.5%). Treatment discontinuation did not differ (OR 1.10, 95% CI 0.39–3.12; I² = 85.8%). Findings were consistent when stratified by platinum use in the control regimen. Conclusions: In HER2-positive early breast cancer, neoadjuvant ADC-based regimens without concurrent chemotherapy achieve pCR comparable to standard chemotherapy while substantially reducing severe toxicity without increasing discontinuation, independent of platinum use. Confirmation in phase III trials with mature survival endpoints is needed.