학술논문
Three-Year Outcomes Following Permissive Cardiotoxicity in Patients on Trastuzumab
Original Article
Original Article
Document Type
Academic Journal
Author
Source
The Oncologist. September 2023, Vol. 28 Issue 9, pe712, 11 p.
Subject
Language
English
ISSN
1083-7159
Abstract
Implications for Practice In patients with HER2-positive breast cancer who developed cardiotoxicity on trastuzumab, more than 90% were able to continue trastuzumab under a strategy of permissive cardiotoxicity without clinical [...]
Introduction: Cardiotoxicity, manifest by reduced left ventricular ejection fraction (LVEF), is the most common reason for the premature discontinuation of trastuzumab. While permissive cardiotoxicity (where mild cardiotoxicity is accepted to enable ongoing trastuzumab) has been shown feasible, the longer-term outcomes are unknown. We aimed to study the intermediate-term clinical outcomes of patients who underwent permissive cardiotoxicity. Materials and Methods: We performed a retrospective cohort study of patients referred to the cardio-oncology service at McMaster University from 2016 to 2021 for LV dysfunction following trastuzumab administration. Results: Fifty-one patients underwent permissive cardiotoxicity. The median (25th-75th percentile) follow-up time from cardiotoxicity onset was 3 years (1.3-4 years). Forty-seven (92%) patients completed trastuzumab; 3 (6%) developed severe LV dysfunction or clinical heart failure (HF) while on trastuzumab and prematurely discontinued therapy. One discontinued trastuzumab by patient choice. At final follow-up after therapy completion, 7 (14%) patients still had mild cardiotoxicity, including 2 who had clinical heart failure and stopped trastuzumab early. Among those with recovered LV function, 50% had normalized LVEF or GLS by 6 and 3 months, respectively, after initial cardiotoxicity. There was no difference in characteristics between those who did or did not recover their LV function. Conclusions: Among patients exposed to permissive trastuzumab cardiotoxicity for HER2-positive breast cancer, 6% were unable to complete planned trastuzumab due to severe LV dysfunction or clinical HF. Although most patients recover their LV function after trastuzumab discontinuation or completion, 14% still have persistent cardiotoxicity by 3-year follow-up. Key words: cardiotoxic agents; cardio-oncology; trastuzumab; retrospective studies; permissive cardiotoxicity. Abbreviations: ACEI, angiotensin converting enzyme inhibitor; ARB, angiotensin receptor blocker; cDLT, cardiac dose- limiting toxicity; GLS, global longitudinal strain; HER2, human epidermal growth factor 2; LVEF, left ventricular ejection fraction; NYHA, New York Heart Association; T-DM1: Trastuzumab emtansine
Introduction: Cardiotoxicity, manifest by reduced left ventricular ejection fraction (LVEF), is the most common reason for the premature discontinuation of trastuzumab. While permissive cardiotoxicity (where mild cardiotoxicity is accepted to enable ongoing trastuzumab) has been shown feasible, the longer-term outcomes are unknown. We aimed to study the intermediate-term clinical outcomes of patients who underwent permissive cardiotoxicity. Materials and Methods: We performed a retrospective cohort study of patients referred to the cardio-oncology service at McMaster University from 2016 to 2021 for LV dysfunction following trastuzumab administration. Results: Fifty-one patients underwent permissive cardiotoxicity. The median (25th-75th percentile) follow-up time from cardiotoxicity onset was 3 years (1.3-4 years). Forty-seven (92%) patients completed trastuzumab; 3 (6%) developed severe LV dysfunction or clinical heart failure (HF) while on trastuzumab and prematurely discontinued therapy. One discontinued trastuzumab by patient choice. At final follow-up after therapy completion, 7 (14%) patients still had mild cardiotoxicity, including 2 who had clinical heart failure and stopped trastuzumab early. Among those with recovered LV function, 50% had normalized LVEF or GLS by 6 and 3 months, respectively, after initial cardiotoxicity. There was no difference in characteristics between those who did or did not recover their LV function. Conclusions: Among patients exposed to permissive trastuzumab cardiotoxicity for HER2-positive breast cancer, 6% were unable to complete planned trastuzumab due to severe LV dysfunction or clinical HF. Although most patients recover their LV function after trastuzumab discontinuation or completion, 14% still have persistent cardiotoxicity by 3-year follow-up. Key words: cardiotoxic agents; cardio-oncology; trastuzumab; retrospective studies; permissive cardiotoxicity. Abbreviations: ACEI, angiotensin converting enzyme inhibitor; ARB, angiotensin receptor blocker; cDLT, cardiac dose- limiting toxicity; GLS, global longitudinal strain; HER2, human epidermal growth factor 2; LVEF, left ventricular ejection fraction; NYHA, New York Heart Association; T-DM1: Trastuzumab emtansine