Background: T-DM1 is approved for the treatment of HER2+ MBC and is currently under investigation for use in the early setting. Cardiac dysfunction is a known side effect of trastuzumab, an anti-HER2 antibody that is a component of T-DM1. However, individual studies were not large enough to permit an adequate understanding of cardiac events (CEs) associated with T-DM1 use. We have conducted a pooled analysis of T-DM1 trials in the advanced setting to understand its incidence, clinical presentation as well as to establish possible risk factors. Methods: we have conducted an individual patient-level pooled analysis of trials testing T-DM1 in HER2+ MBC patients. CEs were defined either as: (1) congestive heart failure (CHF) of any grade or grade 3/4 LVEF drop (symptomatic CHF); (2) cardiac ischemia, (3) cardiac arrhythmia, (4) grade 1/2 LVEF drop. Logistic regression was used to assess possible risk factors (age, prior heart disease, prior hypertension, prior diabetes, prior anthracycline use, concomitant pertuzumab, among others) for CEs. Results: 7 trials with 1961 patients exposed to T-DM1 were obtained. Of these, 1544 received T-DM1 and 417 T-DM1 + Pertuzumab. Median age of patients was 53 years (25-89) and median LVEF at baseline was 63%. 63% of patients had received anthracyclines previously. Symptomatic CHF was reported in 0.7%, cardiac ischemia in 0.1%, cardiac arrhythmia in 0.7% and grade 1/2 LVEF drop in 2%, resulting in a total CE rate of 3.4% (95% CI, 2.6% to 4.3%). No cardiac deaths or cardiac event grade 4 were reported, and only one in five CEs was of grade 3. Multivariate analysis showed patient’s age (odds 5% increase per one-year increase, p < 0.001) and concomitant pertuzumab use (odds ratio 2.1 {95% CI, 1.2 to 3.5}, p 0.007) as significant risk factors for CEs. Further analysis will be presented at the conference. Conclusions: The incidence of CEs in patients receiving T-DM1 was low and most events were not symptomatic. As is the case for trastuzumab, the most common presentation was LVEF drop. Elderly patients receiving T-DM1 should be carefully evaluated for cardiac safety during treatment.