Ado-trastuzumab emtansine (Kadcyla?, Genentech/Roche) significantly extended progression-free survival [PFS] in patients with advanced HER2-positive metastatic and unresectable locally advanced/recurrent breast cancer, thus extending the times people lived without their disease worsening.

This is one of the conclusions from an open-label Phase III study called TH3RESA which evaluated the efficacy and safety of ado-trastuzumab emtansine or T-DM1 in comparison with treatment of the physician’s choice or TPC. The co-primary endpoints were investigator-assessed PFS and OS. Secondary endpoints included objective response rate and safety profile.

The results of the study were presented during ECC2013, the European CanCer Conference, being held in Amsterdam, The Netherlands, September 27 – October 1.


The TH3RESA study included approximately 600 people who had received at least two prior treatments including trastuzumab (Herceptin?, Genentech/Roche), lapatinib (Tykerb?, GSK) and a taxane.[1][2]

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Trial results
The study results show that the risk of disease worsening or death was reduced by 47% for people who received ado-trastuzumab emtansine (HR=0.528, p<0.0001).

These PFS benefit were consistent across subgroups, including age, visceral involvement, number of prior regimens, and treatment of the physician’s choicetype. Furthermore, the T-DM1 safety profile was consistent with prior studies. Fewer grade ?3 adverse events (AEs) overall were reported for T-DM1 vs treatment of the physician’s choice(32.3% vs 43.5%). More grade ?3 thrombocytopenia (4.7% vs 1.6%) was reported with T-DM1. More grade ?3 neutropenia (2.5% vs 15.8%), febrile neutropenia (0.2% vs 3.8%), and diarrhea (0.7% vs 4.3%) were reported with treatment of the physician’s choice.Data for overall survival, the other co-primary endpoint, are not yet mature. In analyzing the data, the researchers did not observe new safety signals.

The data from multiple clinical trials reinforces the benefit of ado-trastuzumab emtansine in patients with advanced HER2-positive metastatic and unresectable locally advanced/recurrent breast cancer.

The study enrolled people with advanced HER2-positive breast cancer who had progressed despite prior treatment with at least two HER2-targeted medicines. It randomized people to receive either treatment with ado-trastuzumab emtansine or a treatment of their physician?s choice. Eighty percent of people treated with physician?s choice received a regimen containingtrastuzumab. The researchers concluded that T-DM1 resulted in a statistically significant improvement in PFS, with fewer grade ?3 AEs than treatment of physician?schoice (TPC) in patients previously treated with ?2 HER2-directed regimens for HER2-positive MBC

?The TH3RESA study is the second large Phase III study in which Kadcylahas improved the amount of time patients with an advanced form of HER2-positive breast cancer lived without their tumor growing,? noted Hal Barron, M.D., chief medical officer and head, Global Product Development at Genentech and Roche. ?We are pleased that the data from multiple clinical trials reinforces Kadcyla?s benefit for people with this aggressive disease.?

Regulatory status
Ado-trastuzumab emtansine, is the first antibody-dryg conjugate or ADCdeveloped by researchers at Roche and Genentech for the treatment of HER2-positive breast cancer. Genentech licenses technology for ado-trastuzumab emtansine under an agreement with ImmunoGen, Inc. Thenew drug was approved in February 2013 by theU.S. Food and Drug Administrationfor the treatment of people with HER2-positive metastatic breast cancer who have received prior treatment with trastuzumab and a taxane chemotherapy.

European evaluation
Ado-trastuzumab emtansine recently received a positive opinion from theEuropean Union?s Committeefor Medicinal Products for Human Use (CHMP) as a single agent for the treatment of adult patients withHER2-positive, unresectable locallyadvanced or metastatic breast cancer who previously received trastuzumab and a taxane, separately or in combination. A European Commission decision on EU marketing approval is expected by the end of the year.

The late-breaking TH3RESA data will be presented at the European Cancer Congress (ECC), by Hans Wildiers, M.D., University Hospital Leuven, Gasthuisberg, Belgium on Saturday Abstract #LBA15, Saturday, September 28, 2013 at 1:03 p.m. CEST).

Table 1-3:A summary of PFS results from ado-trastuzumab arm and trastuzumab-based regimens from the treatment of physician?s choice arm.

For more information:
[1] H. Wildiers, S.B. Kim, A. Gonzalez-Martin, P.M. LoRusso, J.M. Ferrero, M. Smitt, R. Yu, A. Leung, I.E. Kropp. LATE BREAKING ABSTRACT: T-DM1 for HER2-positive metastatic breast cancer (MBC): Primary results from TH3RESA, a phase 3 study of T-DM1 vs treatment of physician’s choice.
Session title: Breast Cancer – Advanced Disease
Session type: Proffered Papers Session
Track: Breast Cancer – Early and Advanced Disease
Abstract number: 15

Clinical trials:
[2] A Study of Trastuzumab Emtansine in Comparison With Treatment of Physician’s Choice in Patients With HER2-Positive Breast Cancer Who Have Received at Least Two Prior Regimens of HER2-Directed Therapy (TH3RESA)(NCT01419197) [Trial]

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