Abstract P1-18-11: Cardiac events in patients with HER2-positive metastatic breast cancer who have low left ventricular ejection fraction prior to initiating treatment with ado-trastuzumab emtansine: A retrospective cohort study using electronic health record data
Authors: Sanglier Thibaut , Shim Jinjoo , Liu Harry , Song Chunyan , Smitt Melanie , Flahavan Evelyn M 
Published: March 2020

Abstract
Background Cardiac events, including left ventricular ejection fraction (LVEF) decrease and congestive heart failure (CHF), are known risks with HER2-targeted antibody-based therapies. Patients with an LVEF of &lt;50% are typically excluded from clinical trials, including ado-trastuzumab emtansine (T-DM1; Kadcyla®) trials; therefore, this study describes patients with an LVEF of 40-49% prior to initiation of treatment with T-DM1 and evaluates the risk of cardiac events. Methods Patients with HER2-positive metastatic breast cancer treated between Jan 1, 2013 and May 31, 2018 were included from the de-identified US-based Flatiron Health electronic health record-derived database. Patients initiating T-DM1 and with a recent LVEF value of 40-49% up to 60 days prior to treatment were included. Patient baseline characteristics (including cardiac history) were described, and the risk of an LVEF drop of &gt;10% points, CHF, and other cardiac events during treatment, and the 84 days following treatment discontinuation, were examined. Results Of approximately 2000 patients with metastatic breast cancer initiating T-DM1 in the database, 32 (1.6%) had an LVEF measurement of 40-49% at baseline (as defined above). These patients had a median age of 64.5 years, median body mass index of 26.1 kg/m2, and 65.6% were white. Median T-DM1 treatment duration was 4.6 months. Cardiac history included prior breast cancer treatment discontinuation due to cardiotoxicity (62.5%), CHF signs and symptoms (34.4%), CHF (28.1%), and prior cardiac hospitalization (18.8%). LVEF monitoring was conducted during treatment for 81.0% of patients who had &gt;2 months of T-DM1 treatment. An LVEF drop of &gt;10% points occurred in four patients (12.5%); CHF events, in five patients (15.6%). Incidence rates were 34.4 and 8.5 per 100 person-years, respectively. These nine events occurred in seven patients, six of whom had relevant cardiac history events recorded in their electronic health record at baseline. CHF signs and symptoms were reported in nine patients (28.1%; 50.5 per 100 person-years) and cardiac tachyarrhythmia in one patient (3.1%; 5.1 per 100 person-years). In a sensitivity analysis that comprised 35 additional patients (N=67) with an LVEF of 40-50% (including overlapping LVEF ranges), the following additional events were recorded: CHF (1); cardiac tachyarrhythmia (1), and CHF signs and symptoms (6). Conclusion A small proportion of patients initiate T-DM1 with low LVEF. The risk of cardiac events observed appears to be consistent with the population profile presenting a cardiac history. The decision for physicians to prescribe T-DM1 in patients with low LVEF should be made in the context of the benefit-risk consideration for cardiac events and the availability of alternative treatment.
Citation Format: Thibaut Sanglier, Jinjoo Shim, Harry Liu, Chunyan Song, Melanie Smitt, Evelyn M Flahavan. Cardiac events in patients with HER2-positive metastatic breast cancer who have low left ventricular ejection fraction prior to initiating treatment with ado-trastuzumab emtansine: A retrospective cohort study using electronic health record data [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P1-18-11.