Two new ADCs outperform chemo in HER2-low breast cancer — but questions remain about their place in a crowded field

Two phase 3 trials presented at the European Society for Medical Oncology (ESMO) 2026 congress in Madrid delivered striking results for patients with HER2-low metastatic breast cancer. Rolditamig deuderuxtecan (TQB2102), a first-in-class biparatopic HER2-targeted ADC, tripled median progression-free survival (PFS) from 5.5 to 16.4 months versus chemotherapy in the APEX-Breast01 trial. Separately, trastuzumab rezetecan more than doubled PFS from 6.8 to 16.4 months in the HORIZON-Breast06 trial, with results simultaneously published in JAMA.

Both drugs showed consistent benefits across hormone receptor (HR)-positive and HR-negative subgroups, with particularly notable gains in the harder-to-treat HR-negative population. Overall survival data remain immature for both agents, though early trends favor the ADCs. The ADC field is rapidly expanding, but experts caution that without head-to-head trials against the current standard of care — trastuzumab deruxtecan (T-DXd, Enhertu) — the clinical positioning of these new agents remains uncertain.

By the Numbers:

• Rolditamig deuderuxtecan (APEX-Breast01): PFS 16.4 vs. 5.5 months (HR 0.29); ORR 68.8% vs. 31%
• Trastuzumab rezetecan (HORIZON-Breast06): PFS 16.4 vs. 6.8 months (HR 0.27); ORR 75.5% vs. 41.2%
• 12-month OS with trastuzumab rezetecan: 90.6% vs. 81.4%
• ILD incidence: ~2.2–2.5% with both ADCs

Why it matters: HER2-low breast cancer represents a large and historically undertreated patient population. These results signal a growing roster of ADC options — but oncologists will need biomarker-driven data and sequencing strategies to determine which patients benefit most from which agent.