Kadcyla (ado-trastuzumab emtansine)

In this cN + cohort, approximately one in six patients eligible for AST had residual disease only in the axilla. Less-invasive axillary staging procedures were associated with a low estimated theoretical risk of missed AST eligibility. However, these findings should be interpreted in light of the modest sample size.

Trastuzumab deruxtecan demonstrated substantial real-world activity after prior T-DM1 exposure, but PFS was significantly shorter compared with T-DM1 naive patients, even after rigorous adjustment for measured confounding. These findings highlight the clinical relevance of antibody drug conjugate sequencing and support prospective studies to define the optimal positioning of T-DXd in HER2 positive mBC treatment algorithms.

P=N/A, N=50, Active, not recruiting, Nagoya City University | Trial completion date: Dec 2025 --> Dec 2026 | Trial primary completion date: Dec 2025 --> Dec 2026

P2, N=37, Recruiting, Dana-Farber Cancer Institute | N=55 --> 37

[225Ac]Ac-Macropa-pertuzumab-PEG6-DM1 is more potent than pertuzumab-PEG6-DM1 against trastuzumab or T-DM1-resistant BC necessitating clinical investigation.

P2, N=920, Active, not recruiting, Hoffmann-La Roche | Recruiting --> Active, not recruiting

The combination of mobocertinib at 80 mg and T-DM1 at 3.6 mg/kg was found feasible and demonstrated potential efficacy for HER2-mutant solid tumors.

Combining T-DXd with SRS demonstrated a favorable safety profile without increasing the risk of radionecrosis. Furthermore, this combination was associated with superior intracranial control, encompassing both local and distant outcomes, supporting the potential of T-DXd combined with SRS as an effective and well-tolerated approach for HER2-positive or -low BCBM.

This review systematically outlines the evolution of HER2 expression profiles, the mechanism of action and limitations of trastuzumab, and focuses on analyzing the breakthrough role of ADCs centered on trastuzumab emtansine (T-DM1) and T-DXd in HER2-low tumors, key clinical evidence, and adverse reaction management. Additionally, it explores the application prospects of combination strategies involving ADCs with chemotherapy and immunotherapy. Finally, the article summarizes challenges facing the current treatment paradigm and outlines future directions for standardized testing and novel therapeutic development.

This review provides a comprehensive overview of the toxicity profiles and underlying mechanisms of HER2-targeted ADCs, with a focus on representative agents such as trastuzumab emtansine (T-DM1) and trastuzumab deruxtecan (T-DXd). Furthermore, we discuss emerging approaches to improve ADC safety through structural optimization, including advances in antibody engineering, linker design, and payload selection. This review aims to guide clinicians and researchers in improving the safety and clinical utility of HER2-targeted ADCs in breast cancer treatment.

Owing to active renal lesions, the patient was treated with prednisolone and cyclophosphamide, which resulted in clinical remission. This case was considered to have T-DM1-associated IgA vasculitis. Although rare, an awareness of the possibility of serious adverse effects associated with drug administration is important.

P2, N=131, Active, not recruiting, Memorial Sloan Kettering Cancer Center | Trial completion date: Feb 2026 --> Feb 2027 | Trial primary completion date: Feb 2026 --> Feb 2027