A phase 2 randomized, controlled trial did not identify major cardiac outcomes among patients receiving adjuvant trastuzumab emtansine (T-DM1) therapy for human growth factor receptor 2- (HER2)-positive breast cancer. These findings were published in NPJ Breast Cancer.
The ATEMPT trial (Clinicaltrials.gov identifier: NCT01853748) recruited 497 patients with stage I HER2-positive breast cancer at 24 centers in the United States between 2013 and 2016. Patients were randomly assigned in a 3:1 ratio to receive T-DM1 or trastuzumab plus paclitaxel. T-DM1 was given at a dose of 3.6 mg/kg on day 1 of each 21-day cycle with a total of 17 cycles or 1 year. Paclitaxel was given at a dose of 80 mg/m2 weekly with a 4 mg/kg loading dose followed by 2 mg/kg trastuzumab for 12 weeks followed by 6 mg/kg trastuzumab every 21 days for 13 cycles. Participants were assessed for cardiovascular outcomes.
The T-DM1 and paclitaxel cohorts were aged median 56 (IQR, 49-63) and 56 (IQR, 47-62) years; 99% and 99% were women; 85% and 82% were White; 42% and 37% had BMI 25 or less; and 85% and 88% had left ventricular ejection fraction (LVEF) of greater than 55%, respectively.
LVEF was largely unchanged from baseline to year 1 among the T-DM1 (median, 63% vs 63%) and paclitaxel (median, 62.5% vs 62%) cohorts, respectively.
Overall, there were 3 patients in the T-DM1 and 2 in the paclitaxel cohorts who developed grade 3 symptomatic cardiac dysfunction during the trial. All but 1 patient did not resume treatment and all but 1 (not reported) had normalized LVEF at follow-up.
An exploratory analysis did not identify any patient characteristics which increased risk for cardiac dysfunction.
The cumulative probability of cardiotoxicity at 6 months was 0.01 (95% CI, 0-0.01) for the T-DM1 and 0.03 (95% CI, 0-0.06) for the paclitaxel cohorts, increasing to 0.02 (95% CI, 0-0.04) and 0.08 (95% CI, 0.02-0.13) at month 12, respectively.
This study was limited by a lack of a systematic cardiac assessment at baseline.
“The low incidence of significant cardiac adverse events in this population during therapy with adjuvant T-DM1 suggests that studies on the cost-effectiveness of cardiac monitoring during adjuvant therapy using anthracycline-free regimens are needed,” the researchers wrote.
Disclosure: Multiple authors declared affiliations with industry. Please refer to the original article for a full list of disclosures.
Barroso-Sousa R, Tarantino P, Tayob N, et al. Cardiac outcomes of subjects on adjuvant trastuzumab emtansine vs paclitaxel in combination with trastuzumab for stage I HER2-positive breast cancer (ATEMPT) study (TBCRC033): a randomized controlled trial. NPJ Breast Cancer. Published online February 16, 2022. doi:10.1038/s41523-022-00385-2