T-DM1 And Pertuzumab Clinical Trial For HER2 Positive Metastatic Breast Cancer: MARIANNE TRIAL
MARIANNE trial evaluates two new drugs for HER2 positive metastatic breast cancer. The two drugs in question are T-DM1 and Pertuzumab. The phase 3 trial has stopped recruiting new participants. The idea of the blog is to discuss the results of the results with regard to two drugs of paramount importance where breast cancer patients are concerned.
While T-DM1 is considered to be a miracle drug for breast cancer and is awaiting FDA approval, Pertuzumab was approved by the FDA last week. Both the drugs are being developed by Roche/Genentech.
The Roche site gives a brief summary of the study which I have here below:
This randomized, 3-arm, multicentre, phase III study will evaluate the efficacy and safety of trastuzumab emtansine (T-DM1) with pertuzumab or trastuzumab emtansine (T-DM1) with pertuzumab-placebo (blinded for pertuzumab), versus the combination of trastuzumab (Herceptin) plus taxane (docetaxel or paclitaxel) in patients with HER2-positive progressive or recurrent locally advanced or previously untreated metastatic breast cancer. Patients will be randomized to 1 of 3 treatment arms (Arms A, B or C). Arm A will be open-label, whereas Arms B and C will be blinded. Target sample size is 1095.
HER2 positive breast cancer has HER2 proteins on the surface of the tumor cells. Trastuzumab recognizes HER2 proteins and binds to them. Pertuzumab is a monoclonal antibody that targets HER2 proteins and binds to them at a different location, thus preventing dimerization of HER2 molecules and disrupting the HER signal pathway. A combination of Trastuzumab and Pertuzumab are more effective in interfering with HER pathways.
T-DM1 is made of Trastuzumab (monoclonal antibody) and a chemotherapy drug DM1. Trastuzumab locates tumor cells and binds to them; the lethal chemotherapy drug is released inside tumor cells destroying them. This is also called the conjugated antibody therapy.
T-DM1 Pertuzumab Clinical Trial Details
- This is a phase 3 trial with 1,100 participants across the world.
- Participants in Group 1 – administered Trastuzumab and docetaxel/paclitaxel
- Group 2 – participants are given Pertuzumab and T-DM1
- Group 3 – participants are given a placebo and T-DM1
- Primary outcome:
- Progression Free Survival (PFS) up to 48 months after the start of study.
- Incidence of adverse events up to 78 months after start of study.
The results of two ongoing T-DM1 clinical trials, EMILIA and MARIANNE, are being looked at as the clincher for Roche/Genentech and breast cancer patients. Late study stage results have shown PFS of 9.6 months when compared to the 6.4 months of the control group. The overall survival rates would be obtained only by 2014.