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Proposal 1702

Title of the Proposed Research

Pooled analysis of cardiac safety of T-DM1 in HER2-positive metastatic breast cancer patients

Lead Researcher

Evandro de Azambuja


Institut Jules Bordet
BrEAST Data Center, Brussels Belgium

Funding Source

This work will be self funded

Potential Conflicts of Interest

Received Honoraria and Travel Grants from Roche. Is PI in Academic studies funded by research grants from Roche to Institut Jules Bordet. Received Travel Grants from Roche. Received Honoraria from Roche. The institut she heads has received multiple grants from Roche to develop academic research.

Data Sharing Agreement Date

24 July 2017

Lay Summary

Breast Cancer is one of the most important disease for women worldwide, both because it is very frequent and because it leads to a high number of deaths. Most women who die after the diagnosis of breast cancer do so because of metastatic disease. Therefore research has in the last decades focused very frequently on understanding better the agressive types of breast cancer in order to develop better treatments for them. 30 years ago a specific type of breast cancer - called HER2-positive, was discovered. This type of breast cancer exploits a normal mechanism of growth in breast cells, the HER2 receptor to overgrow and spread to other parts of the body. This discovery kicked-off an era of incredible evolution in the treatment of this type of breast cancer as drugs that target the HER2 receptor were developed. Trastuzumab-emtansine (T-DM1), is one such drug, recently come into use after proving to be beneficial in patients with metastatic breast cancer. Classically, drugs that target HER2 have caused significant side effects connected to heart function. Individual studies performed with T-DM1 showed few cases of heart toxicity, and therefore understanding the specific clinical course of this toxicity has not yet been possible. Therefore the goal of this study is to gather the results of all the major studies testing T-DM1 (totaling over 2000 patients) in order to provide the best and most complete picture of this important complication. We will study the incidence and seriousness of heart toxicity in patients using T-DM1. We will also investigate if there are risk factors (characteristics that make more likely) for development of heart toxicity. Finally we will study how fast patients recover from this complication. Once the analysis of the data is completed, the results will be presented to the wider community of medical oncology in both clinical symposia and as a publication in scientific journals. This information will be used in deciding which patient can and cannot receive T-DM1, and how to manage patients receiving T-DM1 and develop this toxicity.

Study Data Provided

ROCHE-TDM4374g: A Phase II, single-arm, open-label study, of Trastuzumab-MCC-DM1 adminstered intravenously to patients with HER2-positive metastatic breast cancer
ROCHE-TDM4258g: A phase II, single-arm, open-label study of Trastuzumab-MCC-DM1 administered intravenously to patients with HER2-positive metastatic breast cancer who have progressed while receiving HER2-directed therapy
ROCHE-TDM4688g: A phase II, open-label study to evaluate corrected QT interval effects of Trastuzumab-MCC-DM1 (T-DM1) in patients with HER2-positive recurrent locally advanced or metastatic breast cancer and to evaluate the safety and tolerability of combined T-DM1 and Pertuzumab in patients with early disease progression while receiving T-DM1 alone.
ROCHE-BO21976: A randomized, multicenter phase II study of the efficacy and safety of Trastuzumab-MCC-DM1 vs. Trastuzumab (Herceptin) and Docetaxel (Taxotere) in patients with metastatic HER2-positive breast cancer who have not received prior therapy for metastatic disease.
ROCHE-BO21977: A randomized, Multicenter, Phase III Open-Label study of the efficacy and safety of Trastuzumab-MCC-DM1 vs. Capecitabine + Lapatinib in patients with HER2-Positive locally advanced or metastic breast cancer who have received prior Trastuzumab-based therapy.
ROCHE-BO22589: A Study of Trastuzumab-DM1 Plus Pertuzumab Versus Trastuzumab [Herceptin] Plus a Taxane in Patients With Metastatic Breast Cancer
ROCHE-BO25734: A Phase III Randomized, Multicenter, Two Arm, Open-label Trial to Evaluate the Efficacy of Trastuzumab Emtansine Compared With Treatment of Physician's Choice in Patients With HER2-positive Metastatic Breast Cancer Who Have Received at Least Two Prior Regimens of HER2 Directed Therapy

Statistical Analysis Plan

Publication Citation

The publication citation will be added after the research is published.

Summary Results

Results summary or link will be posted when available.