The role of ado-trastuzumab emtansine in current clinical practice

Objective

This review reflects the literature from 2019 to 2020 on ado-trastuzumab emtansine’s (T-DM1) therapeutic use, clinical controversies, and newest perspectives on use.

Data sources: PubMed was used as a database. Search “ado-trastuzumab emtansine” on June 11th, 2020 resulted in 57 publications: 20 clinical trials, two metanalysis, six randomized controlled studies, 13 reviews, and two systematic reviews. Of the 57 publications, 34 were descriptive of the topic in question and were used for this review.

Data summary: T-DM1 is now used for patients with HER2 breast cancer who have residual disease post surgery after neoadjuvant chemotherapy (KATHERINE trial). Initial success prompted KRISTINE trial, which investigated whether T-DM1 can be used as a neoadjuvant therapy. While it did have fewer adverse events, T-DM1 was inferior to chemotherapy in treating early breast cancer. Noted shortcomings of the drug were toxicity limited C_max, slow rate of internalization, lack of payload bystander effects, and number of resistance mechanisms. Proposed solutions were pre-treatment with metformin to augment drug internalization by the cell, use of second generation anti-HER2 antibody-drug conjugates to overcome developing resistance, payload swapping to increase bystander effect.

Conclusions

While T-DM1 has fewer side-effects, it is inferior to chemotherapy in early breast cancer treatment. More research should be done to overcome resistance pathways, identify rate-limiting intracellular processing pathways, improve bystander, and enhance internalization of the drug. Until more research is done, T-DM1 will continue to be used in HER2 positive breast cancer as well as a few other HER2 expressing tumors that fail to respond to neoadjuvant therapy.