Toxicity decreased with trastuzumab-DM1 vs. trastuzumab plus docetaxel

ESMO 35th Congress

MILAN — Trastuzumab-DM1 proved encouraging as a first-line therapy in patients with HER2-positive metastatic breast cancer when compared with trastuzumab plus docetaxel, according to Edith Perez, MD.

“This is the first ever presentation of an anti-HER2 antibody-drug conjugate used as first-line therapy for patients with advanced breast cancer,” Perez, HemOnc Today Editorial Board member, said in a press release. “We are encouraged by the results. The study demonstrated that trastuzumab-DM1 has very good anti-tumor activity as well as much lower toxicity when evaluated side by side to the older standard. This trial represents the logical step — moving the drug up to patients with newly diagnosed HER2-positive metastases.”

For the randomized trial, Perez and colleagues assigned 137 women to trastuzumab plus docetaxel or trastuzumab-DM1. All participants had HER2-positive metastatic breast cancer and had no prior chemotherapy.

After a median of 6 months follow-up, overall response rate was 48% in patients assigned trastuzumab-DM1 compared with 41% in those assigned trastuzumab plus docetaxel. More importantly, the rates for clinically relevant adverse events were only 37% in women assigned trastuzumab-DM1 compared with 75% in women assigned traztuzumab plus docetaxel.

A larger, phase 3 trial, MARIANNE, is currently underway. PFS, OS at 1 year, mature ORR and duration of response data are expected in 2011.

According to Perez, “This trial evaluates taxane plus trastuzumab against T-DM1 as administered in this study — with a third option being T-DM1 plus pertuzumab — another novel anti-HER2 agent,” said Perez. “I feel privileged to continue our collaborative work to help bring new and better therapeutic options for patients.”

The results are important for two reasons: Firstly, they confirm that in coming years chemotherapy could be replaced by a less toxic compound. Indeed, in the present study, the rates of serious adverse events were much lower in patients given trastuzumab-DM1 compared with the chemotherapy arm. These results suggest that, with the same efficacy, trastuzumab-DM1 could dramatically reduce the toxicities related to chemotherapy. The second important implication of this study is that it proves the concept that linking a monoclonal antibody to a cytotoxic drug leads to an anticancer effect. This could have several implications beyond drugs that target HER2.

– Fabrice André, MD
Institute Gustave Roussy, Villejuif, France

For more information:

Perez EA. #LBA3. Presented at: the 35th Congress of the ESMO; Oct. 8-12, 2010; Milan, Italy.

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