more good reports on T-DM1 for Stage IVs

[Lani]

Trastuzumab-DM1 Is Efficacious and Has a Good Safety Profile in Patients With Metastatic Breast Cancer
Positive results of the first-ever phase 2 study of an anti-HER2 antibody-drug conjugate, trastuzumab-DM1 (T-DM1), as first-line therapy in patients with metastatic breast cancer confirm good efficacy and lower toxicity than standard therapy.

Results of the study will be presented by lead investigator Edith Perez, MD, from the Mayo Clinic, Jacksonville, Florida, here at the 35th European Society for Medical Oncology Congress.

Following on from 2 previous single-group phase 2 studies in extensively pretreated patients with HER2-positive metastatic breast cancer, these results are from the first randomized phase 2 study comparing the efficacy and safety of T-DM1 vs trastuzumab plus docetaxel. Patients involved in the trial all had HER2-positive metastatic breast cancer and had not received prior chemotherapy for metastatic disease.

"We are encouraged by the results. The study demonstrated that T-DM1 has very good anti-tumor activity as well as much lower toxicity when evaluated side by side to the older 'standard,' " said Dr. Perez in a press release.

In this ongoing phase 2 trial, 70 women received treatment with trastuzumab plus docetaxel (6 mg/kg intravenously [8 mg/kg in cycle 1] plus docetaxel at 75 or 100 mg/m2 intravenously on day 1 every 3 weeks), and 67 received T-DM1 (3.6 mg/kg intravenously every 3 weeks). Patients remained on treatment until disease progression or unacceptable toxicity.

Progression-free survival and safety were primary endpoints, whereas secondary endpoints included overall response rate, clinical benefit rate, and overall survival.

After a median of 6 months' follow-up, overall response rate was 48% in patients who received T-DM1 compared with 41% in patients in the trastuzumab plus docetaxel group. Most notably, rates of clinically relevant adverse events (grade > 3) were significantly lower in the T-DM1 group (37%) compared with the rate in patients given trastuzumab plus docetaxel (75%).

Commenting on the results, Fabrice André, MD, from Institut Gustave-Roussy, Villejuif, France, said the results confirm that in coming years, chemotherapy could be replaced by a less toxic compound.

"Indeed, these results suggest that, with the same efficacy, T-DM1 could dramatically reduce the toxicities related to chemotherapy," he said in a statement.

T-DM1 is the first of a novel class of antitumor therapy known as antibody-drug conjugates. T-DM1 consists of 2 existing cancer drugs bound together so that both are delivered to the cancer cells. Trastuzumab is a monoclonal antibody that targets cells that overproduce the protein HER2, and DM1 is a chemotherapy agent that targets microtubules.

Progression-free survival, 1-year overall survival rates, mature overall response rates, and duration of response data are expected in 2011. A phase 3 trial, called MARIANNE, has now begun that assesses trastuzumab plus taxane vs T-DM1, with a third option of T-DM1 plus pertuzumab.

A full report will be available over the coming days, when Dr. Perez presents her findings at the conference.

Coauthors L. Dirix, J. Kocsis, L. Gianni, J. Lu, J. Vinholes, and S. Hurwitz received research/contract support from Roche/Genentech covering costs associated with the conduct of this study. V. Ng, C. Linehan, and S. Agresta are employees and stockholders of Roche. All other authors have disclosed no relevant financial relationships. No financial disclosures on Dr. Andre are available at present.

35th European Society for Medical Oncology Congress: Abstract: LBA3. To be presented October 11, 2010.