Investigational drug slows metastatic breast cancer progression

Jun 11 2012

By Laura Cowen

Trastuzumab emtansine (T-DM1) significantly delays disease progression compared with standard therapy in women with human epidermal growth factor receptor (HER)-2-positive metastatic breast cancer, show study data presented at the American Society of Clinical Oncology Annual Meeting in Chicago, Illinois, USA.

The experimental antibody-drug conjugate T-DM1, not yet approved by the US Food and Drug Administration and only available in clinical trials, delayed disease progression by more than 3 months compared with a standard regimen combining capecitabine and lapatinib.

"The drug worked. It was significantly better than a very effective approved therapy for HER2 overexpressing metastatic breast cancer," said lead study author Kimberly Blackwell (Duke University, Durham, North Carolina, USA) in a press statement.

Blackwell and team randomly assigned 978 patients with histopathologically confirmed HER2-positive metastatic breast cancer to receive treatment with intravenous T-DM1 (3.6 mg/kg every 3 weeks) or oral capecitabine (1000 mg/m² twice daily, days 1‑14 every 3 weeks) plus lapatinib (1250 mg daily) until disease progression or unmanageable toxicity.

After a median follow-up period of just over 1 year, the median progression-free survival time was significantly longer for the patients who received T-DM1 compared with those who received capecitabine plus lapatinib, at 9.6 versus 6.4 months. This was equivalent to a "clinically meaningful" 35% reduction in risk for disease progression, the researchers note.

At 2 years, 65.4% of the T-DM1 patients were alive, compared with 47.5% of the capecitabine plus lapatinib patients. This statistically significant difference did not, however, reach the interim efficacy boundary. A second survival analysis planned for later in the study will provide additional information, say the researchers.

T-DM1 was well tolerated with the most common grade 3 or above adverse events being thrombocytopenia (12.9 vs 0.2% for capecitabine plus lapatinib) and elevation in liver function tests.

These side effects resolved when patients took a break from the drug, Blackwell said. Furthermore, dose reductions were greater for patients in the capecitabine plus lapatinib group than in the T-DM1 group, at 53.4% for capecitabine and 27.3% for lapatinib, compared with 16.3% for T-DM1.

This could be because patients who received capecitabine plus lapatinib experienced more diarrhea (20.7 vs 1.6%), palmar plantar erythrodysesthesia (16.4 vs 0.0%), and vomiting (4.5 vs 0.8%) than those who received T-DM1.

"As a clinician who takes care of a lot of breast cancer patients, I'm pleased that this drug has very little dose-limiting toxicity. Patients don't lose their hair from this drug. For patients facing metastatic breast cancer, this is a breakthrough," Blackwell concluded.

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