Kadcyla (ado-trastuzumab emtansine)

P3, N=1635, Active, not recruiting, Daiichi Sankyo | Trial completion date: Dec 2030 --> Jun 2028 | Trial primary completion date: Dec 2025 --> Jul 2025

T-DM1 shows dose-dependent hepatotoxicity, while cytochrome P450 3A4 (CYP3A4) inhibitors may increase hepatic accumulation of trastuzumab deruxtecan (T-DXd). Trastuzumab mainly induces hepatocellular and cholestatic injury, whereas T-DM1 involves both HER2-dependent and independent pathways. Diagnosis relies on causality assessment, and most cases are reversible with liver function monitoring and timely dose adjustment.

P3, N=562, Not yet recruiting, SWOG Cancer Research Network

P3, N=365, Active, not recruiting, Sichuan Kelun-Biotech Biopharmaceutical Co., Ltd. | Trial primary completion date: Nov 2025 --> Nov 2026

The use of antibody-drug conjugates (ADCs) specific to human epidermal growth factor receptor 2 (HER2), such as ado-trastuzumab emtansine (T-DM1), trastuzumab deruxtecan (Enhertu, T-DXd), and trastuzumab duocarmazine (SYD985), to treat breast cancer patients has been associated with a variety of toxicities including corneal epithelial keratitis. Incubation of normal human corneal epithelial cell lines with trastuzumab or T-DXd demonstrated the capacity for receptor-mediated endocytosis of HER2-targeted therapies by epithelia in the eye. Our findings of HER2 expression in normal human corneal epithelium suggest that the ocular adverse events associated with HER2-targeted ADCs may be driven, at least in part, by an on-target effect.

PHERGain-2 shows meaningful HRQoL preservation, expected HP/T-DM1 toxicity, and an outstanding pCR rate comparable with standard chemotherapy plus HP regimens in this patient population.

P2, N=50, Completed, University College, London | Active, not recruiting --> Completed | Trial completion date: May 2026 --> Nov 2025 | Trial primary completion date: May 2026 --> Nov 2025

Delayed bleeding during T-DM1 therapy may reflect a combination of hematological suppression and vascular vulnerability. Therefore, vigilant surveillance and cautious postoperative rehabilitation are warranted.

P2, N=111, Active, not recruiting, Dana-Farber Cancer Institute | N=82 --> 111

P2, N=38, Active, not recruiting, National Cancer Institute (NCI) | Trial completion date: Mar 2026 --> Mar 2027

T-DM1 biosimilar showed outcomes consistent with those reported for the originator in real-world settings, supporting its broader adoption in both early and advanced HER2-positive breast cancer. Its affordability may improve access and outcomes in resource-limited settings.

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.