Safety Profile of T-DM1 for Metastatic Breast Cancer

Summary and Comment |
July 22, 2014

Safety Profile of T-DM1 for Metastatic Breast Cancer

  1. William J. Gradishar, MD

An analysis of toxicity data from six clinical trials reaffirms the tolerability of this new agent.

  1. William J. Gradishar, MD

The antibody–drug conjugate trastuzumab emtansine (T-DM1) was recently approved by the FDA for patients with HER2-positive metastatic breast cancer previously treated with trastuzumab and taxane. Within treatment pathways, T-DM1 has been positioned as second-line therapy following disease progression on trastuzumab-based therapy. The efficacy results of T-DM1 were impressive, and the adverse effects in individual trials were manageable.

To further define the safety profile of this new agent, investigators conducted an integrated analysis of toxicity data from six industry-supported, randomized, phase II and III trials involving 884 patients with HER2-positive metastatic disease who received T-DM1.

The most common all-grade, adverse events were fatigue (46%), nausea (43%), thrombocytopenia (32%), headache (29%), and constipation (27%). The most commonly reported grade 3 or 4 events, besides fatigue (3.2%), were laboratory abnormalities: thrombocytopenia (grade 3, 9.5%; grade 4, 2.4%), increased serum aminotransferases AST (4.3%) or ALT (3.1%), hypokalemia (3.3%), and anemia (2.9%). Asian patients experienced more grade 3 or 4 events, largely accounted for by more-frequent thrombocytopenia in this population. Discontinuation of T-DM1 therapy occurred in 7.0% of patients, most commonly because of laboratory abnormalities: thrombocytopenia (1.5%), increased AST (0.8%), and increased ALT (0.5%). Three patients with clinical or laboratory evidence of portal hypertension were found to have biopsy-confirmed nodular regenerative hyperplasia. Of the patients with grade 3 or 4 thrombocytopenia, grade 1 nosebleeds were the most common consequence (43.8%). Hypersensitivity or infusion reactions occurred in 6.9% of patients but were largely grade 1 or 2, and only a single grade 3 infusion reaction occurred and resolved on day 1 of the first cycle.


The availability of T-DM1 has expanded the treatment options for patients with progressive HER2-positive, metastatic breast cancer. With a very tolerable safety profile, the investigation of T-DM1 in combination with other agents earlier in metastatic breast cancer and as an adjuvant therapy is likely to broaden its indication in the future.

Editor Disclosures at Time of Publication

  • Disclosures for William J. Gradishar, MD at time of publication Consultant / Advisory board Biologics, Inc. Editorial boards Clinical Breast Cancer; Journal of Clinical Oncology; Oncology Leadership positions in professional societies American Society of Clinical Oncology (Nominating Committee Chair)


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