Abstract P4-21-23: A retrospective evaluation of cardiovascular recovery and oncologic outcomes associated with interrupted and continuous adjuvant trastuzumab in the setting of mild left ventricular dysfunction
Authors: Gibson JD , Yao RJR , Davis MK , Simmons CE 
Published: March 2017

Background: Trastuzumab is a monoclonal antibody that targets the HER2 receptor. In the adjuvant setting, 12 months of trastuzumab therapy has been shown to significantly reduce the risk of cancer recurrence. However, treatment with trastuzumab may also be associated with a decline in left ventricular (LV) function that, in most cases, will recover after trastuzumab therapy is stopped. When severe or symptomatic left ventricular dysfunction (LVD) occurs, trastuzumab is generally held with the intention of restoring cardiac function. It is less clear how to manage trastuzumab to optimize both cancer therapy and cardiovascular care when mild, asymptomatic drops in LV function are observed. The intention of this study was to assess how trastuzumab was managed immediately after the development of mild LVD in a non-trial setting and evaluate these outcomes.

Methods: Patients who received adjuvant trastuzumab therapy for breast cancer between September 2005 and September 2010 in British Columbia were identified. Heart function imaging data for these patients were subsequently reviewed to identify those who experienced either a drop in LV ejection fraction (LVEF) to 40-49% or a greater than 15% drop in LVEF relative to their pre-chemotherapy baseline to a final LVEF ≥50%. The charts of patients who met these inclusion criteria were then reviewed for demographic information, comorbidities, trastuzumab dosing regime, subsequent cardiac events, and breast cancer outcomes.

Results: A total of 171 patients were included in this study. 121 (70.8%) patients had an immediate hold in their trastuzumab therapy while the remaining 50 (29.2%) continued with their next scheduled dose. The number of patients who experienced a cancer relapse event in the therapy interruption and continuation groups were 21 (17.4%) and 5 (10.0%), respectively (P = 0.25). Cardiovascular events in the therapy interruption group included a subsequent drop in LVEF to &lt;40% in 11 (9.1%) patients, long-term congestive heart failure (CHF) in 2 (1.7%) patients, and 1 (0.9%) death related to CHF. Cardiovascular events in the therapy continuation group included a subsequent drop in LVEF to &lt;40% in 3 (6.0%) patients and long-term CHF in 1 (2.0%) patient. 24 (19.8%) patients in the therapy interruption group had a final LV function measurement that had fallen more than 10% below their baseline value while 12 (24.0%) patients in the therapy continuation group met this criterion (P=0.54). The mean numbers of adjuvant trastuzumab doses administered in the therapy interruption and continuation groups were 11.3 and 14.3, respectively. Finally, mean follow up times for the therapy interruption and continuation groups were 5.6 and 5.8 years, respectively.

Conclusions: Continuing trastuzumab immediately after the development of mild LVD did not appear to be associated with an increased risk of long-term cardiovascular events. However, holding trastuzumab immediately after the development of mild LVD appeared to be associated with a 7.4% absolute risk increase in breast cancer recurrence. While these results are not statistically significant, they are concerning and warrant further investigation.

Citation Format: Gibson JD, Yao RJR, Davis MK, Simmons CE. A retrospective evaluation of cardiovascular recovery and oncologic outcomes associated with interrupted and continuous adjuvant trastuzumab in the setting of mild left ventricular dysfunction [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P4-21-23.