Abstract P5-18-02: Trastuzumab interruption for treatment-induced cardiotoxicity in HER2 positive early breast cancer

Abstract

Abstract Background Trastuzumab (H) improves outcomes among patients with HER2-positive breast cancer but is associated with a risk of treatment-induced cardiotoxicity (TIC), especially when administered after an anthracycline (A). H interruption is recommended for significant asymptomatic or symptomatic declines in left ventricular ejection fraction (LVEF). It is unclear how frequently TIC leads to H interruption, and the subsequent management is variable in clinical practice. Methods Patients (pts) with HER2-postive early breast cancer receiving adjuvant H with chemotherapy between January 2005 and October 2010 were studied (n=608). Tumor characteristics, chemotherapy regimen, cardiac risk factors, LVEF (at baseline and during treatment), and treatment interruption were obtained from the medical record. We evaluated the incidence, time of occurrence, management, and associated risk factors of H interruption due to TIC. Results Median age was 51 years (range 26-81); 488 (80%) pts had A prior to H administration. H was interrupted in 108 (18%) pts. Cumulative dose of H was lower among pts in the interrupted group (median 86 vs. 108 mg/kg, p < 0.0001). The most common reason for interruption was TIC (66 of 108 pts): 20 (30%) had symptomatic congestive heart failure and 46 (70%) had asymptomatic decline in LVEF. Of the 66 pts, 55 (83%) were referred to a cardiologist and 36 (55%) were prescribed a new cardiac medication. The mean LVEF at baseline, at time of cardiotoxicity diagnosis, and at follow-up after interruption of H was 63%, 45%, and 55%, respectively. Pts with H interruption for TIC were older (54 vs. 50 years, p=0.014) with lower LVEF before A (63 vs. 67%, p<0.0001) and before H therapy (62% vs. 67%, p<0.0001), compared to those with continuous H treatment. Thirty-three of 66 pts were re-treated with H, and 5 pts had a significant recurrent decline in LVEF. Conclusion At our institution, interruption of H therapy is common and most often due to TIC, from both A and H, with the majority of pts receiving A prior to H. Risk factors associated with H interruption were older age and lower LVEF prior to A and H administration. Cardiac dysfunction improved after interruption of treatment but did not fully recover to baseline. Strategies to prevent cardiotoxicity and minimize H treatment interruption should be investigated to prevent persistent LV dysfunction in affected pts. Citation Format: Anthony F Yu, Nandini U Yadav, Betty Y Lung, Anne A Eaton, Howard T Thaler, Clifford A Hudis, Chau T Dang, Richard M Steingart. Trastuzumab interruption for treatment-induced cardiotoxicity in HER2 positive early breast cancer [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr P5-18-02.