Abstract PS13-21: Cardiac function in patients receiving trastuzumab for HER2+ metastatic breast cancer with left ventricular ejection fraction&lt;50% at baseline
Authors: Bouwer Nathalie I , Steenbruggen Tessa G , Rier Hanah N , Kitzen Jos JEM , Smorenburg Carolien H , Van Bekkum Marlies L , Tije Albert J Ten , De Jong Paul C , Drooger Jan C , Holterhues Cynthia , Kofflard Marcel JM , Boersma Eric , Sonke Gabe S , Levin Mark-David , Jager Agnes 
Published: February 2021

Research objectives and rationale Trastuzumab greatly enhances the efficacy of treatment in HER2+ metastatic breast cancer (MBC). Due to its potential to induce cardiomyopathy, however, trastuzumab is contraindicated in patients with baseline left ventricular ejection fraction (LVEF) &lt;50%, although this criterion is sometimes waived. We investigated the effect of trastuzumab on the cardiac function in a real-world cohort of patients with HER2+ MBC with a reduced baseline LVEF, i.e. baseline LVEF &lt;50%. Methods We collected data on patients with HER2+ MBC who received at least one cycle of trastuzumab-based treatment between 2000 and 2014 in eight Dutch hospitals. Eligible patients had baseline LVEF 40-50%. Data were retrospectively collected from medical files using case record forms. Primary endpoint was severe cardiotoxicity defined as LVEF &lt;40%. We also investigated whether severe cardiotoxicity was reversible. Reversibility was defined as any LVEF increase to a value &lt;5% below baseline value and irreversibility as any absolute LVEF increase &lt;10% from lowest value to &gt;5% below baseline. Exploratory, we compared the incidence of severe cardiotoxicity in patients with and without cardioprotective medication at start trastuzumab. Results Of the 758 patients identified with HER2+ MBC, 41 patients were included with a LVEF &lt;50% at start of trastuzumab treatment. The median LVEF at start was 46% with an interquartile range (IQR) of 42-48%. The median duration of trastuzumab treatment was 14 months (IQR 8-32 months). During this period, 16 patients (39%) developed severe cardiotoxicity. The median time to severe cardiotoxicity was 7 months (IQR 4-10 months). Severe cardiotoxicity was reversible in 6 patients (43%), partly reversible in 4 patients (29%) and irreversible in 4 patients (29%). Two patients were lost-to-follow-up. Of the 6 patients with reversible severe cardiotoxicity, trastuzumab treatment was continued in 2 patients (33%), interrupted &lt;6 months in 1 patient (17%) and discontinued in 3 patients (50%). Of the 4 patients with irreversible severe cardiotoxicity, trastuzumab treatment was interrupted in 1 patient (25%) and discontinued in the other 3 patients (75%). In total, 12 patients (29%) received cardioprotective medications, i.e. beta-blocker (n=4), ACE inhibitor (n=4) or both (n=4), at start of trastuzumab treatment. In patients who received cardioprotective medications at start trastuzumab severe cardiotoxicity was less often observed compared to patients who did not received cardioprotective medications at start of trastuzumab (17% vs 48%, p=0.059, Table). Conclusion In our cohort of patients with HER2+ MBC, trastuzumab could be safely administered in 61% without developing severe cardiotoxicity despite an impaired LVEF at the start of trastuzumab treatment. Severe cardiotoxicity was (partly) reversible in about two thirds of the cases. Risks and benefits of trastuzumab use in this vulnerable population must be balanced carefully. The use of cardioprotective medications at start of trastuzumab treatment might reduce the risk of developing severe cardiotoxicity.

Clinical characteristics of patients with and without cardioprotective medication from start trastuzAll patients (n=41)Patients with cardioprotective medication from start trastuzumab (n=12)Patients without cardioprotective medication fromStart trastuzumab (n=29)P-valueSevere cardiotoxicitya, n (%)16 (39)2 (17)14 (48)0.059Time to cardiotoxicity, months [IQR]7 [3 - 12]6 [not reached - 8]8 [4 - 11]0.515Reversibilityb, n (%)No4 (29)1 (8)3 (10)0.260Partial4 (29)0 (0)4 (14)Yes6 (43)0 (0)6 (21)Trastuzumab treatment , n (%)Continued27 (66)7 (58)20 (69)0.796Interrupted6 (15)2 (17)4 (14)Discontinued8 (20)3 (25)5 (17)LVEF, median % (IQR)Baseline46 [42 - 48]47 [44 - 49]46 [43 - 48]0.177Nadir42 [33 - 45]43 [40 - 47]40 [32 - 45]0.322Highest53 [50 - 57]52 [50 - 57]53 [49 - 58]0.761Difference nadir and highest13 [9 - 20]11 [7 - 19]13 [10 - 21]0.464Cardiac symptoms, n (%)16 (39)4 (33)12 (41)0.515

Citation Format: Nathalie I Bouwer, Tessa G Steenbruggen, Hanah N Rier, Jos JEM Kitzen, Carolien H Smorenburg, Marlies L Van Bekkum, Albert J Ten Tije, Paul C De Jong, Jan C Drooger, Cynthia Holterhues, Marcel JM Kofflard, Eric Boersma, Gabe S Sonke, Mark-David Levin, Agnes Jager. Cardiac function in patients receiving trastuzumab for HER2+ metastatic breast cancer with left ventricular ejection fraction&lt;50% at baseline [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS13-21.