# TrAstuzumab Cardiomyopathy Therapeutic Intervention with Carvedilol (TACTIC) Trial

> **NIH NIH R01** · MAYO CLINIC ROCHESTER · 2022 · $825,573

## Abstract

PROJECT SUMMARY
Trastuzumab, a monoclonal directed against the human epidermal growth factor (EGF) receptor-2 (HER-2),
revolutionized HER-2-positive breast cancer treatment, albeit, with the therapy-limiting side effect of cardiotoxicity.
We found that 40% of patients experience a left ventricular ejection fraction (LVEF) decline >10% during
trastuzumab therapy, and 4% develop heart failure (HF). In 25-50% of these cases, the LVEF decline is not fully
reversible, even with cardiovascular therapy. Genetic contributors to cardiac vulnerability and the best
cardiovascular management strategy are unknown. A critical need exists for cardio-preventive approaches in
patients at risk of trastuzumab-induced cardiotoxicity.
The current application’s objective is to evaluate cardio-protective approaches using carvedilol in curative-intent
trastuzumab for HER-2-positive breast cancer. Our central hypotheses are that a pre-emptive preventive
approach (cardiovascular therapy with the beta-blocker carvedilol started before trastuzumab therapy), or a reactive
preventive approach (cardiovascular therapy started in response to early subclinical signs of cardiac dysfunction/
injury, i.e. cardiac troponin elevation or abnormal global longitudinal strain (GLS)) will reduce cardiotoxicity
compared with a standard “wait-and-see” approach (carvedilol prescribed once cardiotoxicity has occured).
We furthermore hypothesize that carvedilol extension beyond the active trastuzumab treatment leads to superior
outcomes and that pharmacogenomics can predict cardiotoxicity non-responsive to cardiovascular therapy with
carvedilol. This clinical trial will test these hypotheses, involving 450 adult breast cancer patients beginning a year of
curative-intent trastuzumab therapy, randomized to either a preemptive, a reactive, or reference care approach.
This study addresses three specific study aims:
Aim 1: To compare the incidence of a) HF or asymptomatic decline in LVEF by >10% in those with LVEF ≥50% or
≥5% in those with LVEF decrease to a nadir of <50% (lead primary aim #1), and b) reversible LVEF decline to
within 5% of baseline (secondary primary aim #1) with a pre-emptive, reactive, and “wait-and-see” approach of
carvedilol initiation in breast cancer patients over the course of adjuvant trastuzumab therapy. This aim addresses
the question of initiation of cardioprotective efforts for trastuzumab therapy.
Aim 2: To compare the delta change in LVEF from completion to 1 year post-completion of trastuzumab therapy
between a cardioprotective approach with carvedilol confined the duration of trastuzumab therapy or extended for 1
year thereafter. This aim addresses the question of duration of cardioprotective efforts for trastuzumab therapy.
Aim 3: To test the association of predefined genetic variants with change in GLS and LVEF during and after
trastuzumab therapy, adjusted for treatment arm. This aim is to identify genetic variants that predict trastuzumab
cardiotoxicity in gener...

## Key facts

- **NIH application ID:** 10357789
- **Project number:** 5R01CA233610-04
- **Recipient organization:** MAYO CLINIC ROCHESTER
- **Principal Investigator:** Joerg Herrmann
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $825,573
- **Award type:** 5
- **Project period:** 2019-03-01 → 2025-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10357789

## Citation

> US National Institutes of Health, RePORTER application 10357789, TrAstuzumab Cardiomyopathy Therapeutic Intervention with Carvedilol (TACTIC) Trial (5R01CA233610-04). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10357789. Licensed CC0.

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