Trastuzumab emtansine (TDM-1) provided similar progression-free survival, compared with trastuzumab plus taxane for first-line treatment of human epidermal growth factor receptor 2–positive advanced breast cancer, but proved more tolerable to patients.
In the phase III MARIANNE study, 1,095 patients with HER2-positive advanced breast cancer were randomized 1:1:1 to trastuzumab plus taxane, T-DM1 plus placebo, or T-DM1 plus pertuzumab. Median duration of follow-up was approximately 35 months.
Dr. Edith Perez
Incidence of adverse events equal to or greater than grade 3 were 54.1% for trastuzumab plus taxane, 45.4% for T-DM1, and 46.2% for T-DM1 plus pertuzumab, respectively. Adverse events led to discontinuation of treatment by a greater number of patients receiving trastuzumab plus taxane, compared with patients in other arms of the study.
Objective response rate and median response duration in those patients who achieved a response were 67.9% and 12.5 months for trastuzumab plus taxane, 59.7% and 20.7 months for T-DM1, and 64.2% and 21.2 months for T-DM1 plus pertuzumab, respectively.
Subgroup analysis demonstrated a numerical trend for an increased relative treatment effect for patients who, during early breast cancer treatment, had received either HER2-directed therapy or taxanes.
Time to clinically meaningful decrease in health-related quality of life was a median of 3.6 months for trastuzumab plus taxane, 7.7 months for T-DM1, and 9.0 months for T-DM1 plus pertuzumab.
A left ventricular ejection fraction of less than 50% accompanied by a greater than or equal to 15 percentage-point decease from baseline occurred in 0.8% of T-DM1 patients, compared with 4.5% with trastuzumab plus taxane and 2.5% with T-DM1 plus pertuzumab.
The authors note that the breast cancer guidelines of the National Comprehensive Cancer Network include T-DM1 as a first-line treatment option for patients with HER2-positive metastatic breast cancer who are not considered suitable for treatment with the preferred regimen of pertuzumab, trastuzumab, and a taxane.