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Multiple phase 3 trials presented at ESMO 2026 show that novel antibody-drug conjugates (ADCs) dramatically outperform chemotherapy in HER2-low advanced breast cancer. Trastuzumab rezetecan more than doubled progression-free survival (16.4 vs. 6.8 months), while rolditamig deuderuxtecan tripled it (16.4 vs. 5.5 months), and izalontamab brengitecan doubled PFS in heavily pretreated HR-positive disease. The big question now: how to sequence this growing arsenal of ADCs.
The ESMO 2026 congress spotlighted a surge of new antibody-drug conjugates (ADCs) challenging chemotherapy in HER2-low advanced breast cancer — a subtype that now accounts for the majority of metastatic breast cancer cases. Three phase 3 trials, all conducted in China, reported striking progression-free survival (PFS) gains, adding to the already-approved trastuzumab deruxtecan (T-DXd, Enhertu) and intensifying debate over how to best sequence these agents.
Trastuzumab rezetecan (HORIZON-Breast06) and rolditamig deuderuxtecan (APEX-Breast01) each achieved a median PFS of 16.4 months versus roughly 5.5–6.8 months with chemotherapy in largely chemo-naïve patients. Izalontamab brengitecan (iza-bren; PANKU-Breast01), a first-in-class bispecific EGFR×HER3 ADC, doubled PFS to 8.2 months versus 4.0 months in heavily pretreated HR-positive, HER2-negative patients. All three agents carried significant hematologic toxicity, and overall survival data remain immature.
By the Numbers
Why it matters: With multiple ADCs sharing the same topoisomerase I inhibitor payload and HER2 target, cross-resistance after sequential use is a real concern. Experts are calling for head-to-head trials, biomarker-driven patient selection, and regulatory harmonization so that data from China-only trials can inform global approvals.
