Trial design

The MARIANNE trial was an international trial involving up to 1092 patients with progressive or recurrent locally advanced or previously untreated metastatic HER2-positive breast cancer.

The study aimed to evaluate the efficacy and safety of trastuzumab emtansine (also known as T-DM1; brand name Kadcycla). Trastuzumab emtansine is an antibody-drug conjugate consisting of trastuzumab (brand name Herceptin® and others), a linker molecule and the cytotoxic (chemotherapeutic) agent DM1. Trastuzumab emtansine was a new drug at the time the trial began. (Trastuzumab is an antibody-based drug which binds to HER2 receptors in patients with HER2-positive breast cancer.) 

The MARIANNE study compared the use trasruzumab emtansine alone, or in combination with another anti-HER2 antibody-based drug, pertuzumab, when given after surgery or radiotherapy for the treatment of metastatic breast cancer.  The results from these patients were compared with those from women given trastuzumab plus a taxane. 


The final results of MARIANNE were published in 2019. They showed that trastuzumab emtansine (T-DM1) with or without pertuzumab showed noninferior* progression-free survival and better tolerability than trastuzumab plus a taxane for the treatment of HER2-positive advanced breast cancer. The researchers concluded that the results supported the use of trastuzumab emtansine as a first-line treatment for patients with HER2-positive metastatic breast cancer who are deemed unsuitable for taxane-based therapy. 

*noninferior means that the treatment being tested in the trial worked as well as the treatment it was compared to, but was not significantly better. Noninferiority trials are often used when the new treatment may have advantages other than efficacy, such as being less toxic or more convenient that the standard therapy.