Center for Global Research Data

Validation of trastuzumab-emtansine (T-DM1) Toxicity Score to predict response to T-DM1 treatment in metastatic breast cancer

Lead Investigator: Shou-Ching TANG, University of Mississippi Medical Center (UMMC) Cancer Center and Research Inst.
Title of Proposal Research: Validation of trastuzumab-emtansine (T-DM1) Toxicity Score to predict response to T-DM1 treatment in metastatic breast cancer
Vivli Data Request: 7136
Funding Source: None
Potential Conflicts of Interest: None

Summary of the Proposed Research:

Breast cancer is the most common female cancer, with about 1.6 million new cases diagnosed annually. Further, it is also the leading cause of cancer-related deaths in women worldwide. In the United States, breast cancer accounts for 30% of all new cancer diagnoses and 15% of cancer-specific mortality in women. Approximately 268 600 new breast cancer cases and 41 760 related deaths have been reported in 2019. About 20% of all breast cancers overexpress the HER2 receptor, which is known to correlate with shortened survival. The monoclonal antibody trastuzumab has demonstrated major benefits for metastatic disease for two decades now, stimulating efforts to greatly expand the role of this drug in HER2-positive disease. This became clinically important in breast cancer when the use of trastuzumab-emtansine (T-DM1) demonstrated a survival benefit in metastatic HER2+ breast cancer.

Our study aimed to investigate whether the systemic toxicities of TDM1 predict tumor response in HER2+ metastatic breast cancer. We hypothesized that the systemic toxicities of T-DM1 may be due to the free emtansine released from lysed tumor cells, and therefore may correlate with the efficacy of the drug. Once our finding is validated from the large patient cohort, the clinician may use the toxicity score to predict the patient outcome from T-DM1 treatment. In addition, it will reassure the physician and patient not to back off prematurely from the therapy in face of systemic toxicity. Its predictive value may be further expanded to other antibody-drug conjugates, especially those with the non-cleavable linkers.

Requested Studies:

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 Metastatic Breast Cancer Who Have Received Prior Trastuzumab-Based Therapy
Data Contributor: Roche
Study ID: NCT00829166
Sponsor ID: BO21977

A Randomized, 3 Arm, Multicenter, Phase III Study to Evaluate the Efficacy and the Safety of T-DM1 Combined With Pertuzumab or T-DM1 Combined With Pertuzumab-Placebo (Blinded for Pertuzumab), Versus the Combination of Trastuzumab Plus Taxane, as First Line Treatment in HER2 Positive Progressive or Recurrent Locally Advanced or Metastatic Breast Cancer
Data Contributor: Roche
Study ID: NCT01120184
Sponsor ID: BO22589

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
Data Contributor: Roche
Study ID: NCT01419197
Sponsor ID: TDM4997g