Tuesday, October 2, 2012

Roche's novel antibody drug conjugate T-DMI delivers a blow to GSK's Tykerb (Lapatinib)

At ESMO Roche announced detailed data from the Phase III EMILIA study. The EMILIA study  compared Roche's T-DM1 head to head with the current standard of care (Tykerb + Xeloda) in 991 metastatic HER2+ve breast cancer patients who have undergone previous treatment with Herceptin and Taxane.

Results of the Trial
• Median PFS was 9.6 months in the group receiving T-DM1 and 6.4 months in the group treated with lapatinib plus capecitabine (hazard ratio for progression or death from any cause: 0.65; 95% CI 0.55 to 0.77; >
• The median overall survival at the second interim analysis (331 deaths) was 30.9 months vs. 25.1 months, respectively (HR 0.68; 95% CI, 0.55 to 0.85; P<0 .001=".001" boundary="boundary" crossed="crossed" efficacy.="efficacy." for="for" p="p" stopping="stopping" the="the" this="this">
• Estimated 1-year survival rates were 85.2% in the T-DM1 group and 78.4% in the lapatinib–capecitabine group; rates at 2 years were 64.7% and 51.8%, respectively.

• The objective response rate was 43.6% with T-DM1 vs. 30.8% with lapatinib plus capecitabine (P<0 .001=".001" p="p">
• Results for all other secondary endpoints favoured T-DM1.

• Rates of grade 3 or 4 adverse events were higher with lapatinib plus capecitabine than with T-DM1 (57% vs. 41%). The incidences of thrombocytopenia and increased serum aminotransferase levels were higher with T-DM1, whereas the incidences of diarrhoea, nausea, vomiting, and palmar–plantar erythrodysesthesia were higher with lapatinib plus capecitabine.

Consistent and favourable outcomes seen in patients treated with T-DM1 in this study indicate that it has efficacy in HER2-positive breast cancer, and that its safety profile shows intracellular delivery of a cytotoxic agent specifically to HER2-overexpressing cells improves the therapeutic index by minimising exposure of normal tissue.