Saturday, March 31, 2012

EMILIA Study Results: Roche's Trastuzumab Emtansine (T-DM1) Delays Metastatic Breast Cancer Progression

Trastuzumab Emtansine (T-DM1) increases progression-free survival (PFS) in metastatic breast cancer patients compared to patients who received lapatinib (Tykerb; GlaxoSmithKline Plc) and  capecitabine (Xeloda; Roche) combination, Roche made the announcement today in a press release.  The overall surivival (OS) data is not mature yet.


T-DM1 is an armed antibody (aka antibody drug conjugate, ADC) which contains a potent chemotherapy drug maytansine linked via a linker to the Her2 receptor specific drug trastuzumab (Herceptin).  T-DM1 has an advantage over trastuzumab because it allows targeting and killing of cancer cells with lower Her2 expression.  The conjugation technology is licenced from ImmunoGen

About EMILIA  (TDM4370g/BO21977) Study
  • Phase 3 open-label trial
  • Patientswith Her2-positive metastatic breast cancer previously treated with trastuzumab and taxane-based chemotherapy whose disease had worsened.
  • Total participants = 991.
  • Trastuumab emtansine arm: T-DM1 alone 3.6 mg/kg every three weeks.
  • Lapatinib and  capecitabine arm: 1250 mg lapatinib daily and 2000 mg/m2 Xeloda on days 1-14 every three weeks.
  • Endpoints: "The co-primary efficacy endpoints of the study are PFS (as assessed by an independent review committee) and OS.  Other study endpoints include safety profile, one-year and two-year survival rates, PFS as assessed by investigator, overall response rate, duration of response and quality of life." -- from Roche press release

Two related phase 3 trials:
  1. MARIANNE is comparing three different regimens (trastuzumab emtansine alone, trastuzumab emtansine plus pertuzumab, and Herceptin plus a taxane chemotherapy) in people with HER2-positive mBC who have not been previously treated for their metastatic disease.
  2. TH3RESA is comparing trastuzumab emtansine with physician's choice of treatment in people with HER2-positive metastatic breast cancer who have already received both Herceptin and lapatinib.
The regulatory filing are planned this year -- Marketing Authorisation Application to the European Medicines Agency (EMA) by Roche for use in HER2-positive metastatic breast cancer, and Biologics License Application to U.S. FDA.

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