Kadcyla (ado-trastuzumab emtansine)

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

She received first-line chemotherapy with trastuzumab, pertuzumab, and docetaxel, followed by maintenance anti-HER2 therapy and surgery for local disease control. This case may represent an exceptional response to T-DM1 and highlights the potential for durable complete remission in selected patients with HER2-positive metastatic breast cancer. Further investigation is warranted to identify predictive factors for exceptional responses and to determine optimal treatment duration.

P3, N=608, Completed, Daiichi Sankyo | Active, not recruiting --> Completed

Notably, RC48 retained strong activity in BT474-derived sublines resistant to T-DM1, lapatinib, or neratinib, inducing cell cycle arrest, apoptosis, and caspase activation in all resistant models. Together, these findings identify disitamab vedotin as a potent next-generation HER2-targeting ADC with the unique capacity to overcome acquired resistance to HER2-directed therapies. RC48 represents a promising therapeutic strategy for patients with refractory HER2-positive breast cancer and warrants further clinical investigation.

P1/2, N=210, Active, not recruiting, Hoffmann-La Roche | Trial completion date: Jul 2026 --> Jul 2027 | Trial primary completion date: Jul 2026 --> Jul 2027

P2, N=55, Recruiting, Dana-Farber Cancer Institute | Trial completion date: Feb 2027 --> Feb 2029 | Trial primary completion date: Feb 2026 --> Feb 2028

P1/2, N=320, Active, not recruiting, Ascendis Pharma Oncology Division A/S | Recruiting --> Active, not recruiting