Trastuzumab Emtansine (T-DM1) — Drug Monograph

Brand names: Kadcyla

Drug class: Antibody-Drug Conjugate

Mechanism of Action

Conjugate of trastuzumab with the maytansine derivative DM1, linked via a stable thioether linker (MCC). Binds HER2, is internalized, and DM1 is released intracellularly — inhibiting microtubule assembly. Combines the ADCC and signaling-inhibition mechanisms of trastuzumab with the cytotoxic activity of DM1. Importantly, DM1 stays inside the cell (no bystander killing due to non-cleavable linker).

FDA Indications

• HER2-positive, unresectable locally advanced or metastatic breast cancer — previously treated with trastuzumab and a taxane
• HER2-positive early breast cancer — adjuvant treatment of residual invasive disease after neoadjuvant paclitaxel/trastuzumab (KATHERINE trial)

Common Side Effects

• Fatigue
• Nausea
• Musculoskeletal pain
• Thrombocytopenia
• Elevated liver enzymes
• Headache
• Constipation
• Peripheral neuropathy

Clinical Pearl

T-DM1 (Kadcyla) vs. T-DXd (Enhertu) — these are completely different drugs despite both being trastuzumab-based ADCs. Kadcyla is used in HER2-positive breast cancer as a later-line option or adjuvant after neoadjuvant failure. Enhertu (trastuzumab deruxtecan) is a newer, more potent ADC with a cleavable linker (enabling bystander killing) and has largely moved to second-line for metastatic HER2+ and even HER2-low breast cancer.

Related Therapies & Mechanisms

• Datopotamab deruxtecan-dlnk (Datroway) — Antibody-Drug Conjugate · Breast
• Sacituzumab govitecan (Trodelvy) — Antibody-Drug Conjugate · Breast
• Trastuzumab deruxtecan (Enhertu) — Antibody-Drug Conjugate · Breast
• Belantamab mafodotin (Blenrep) — Antibody-Drug Conjugate