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Publications

Journal Article Clinical Trial, Phase I Randomized Controlled Trial Ppublish

PubMed: 40172740 DOI: 10.1007/s10549-025-07636-3

Risk-guided cardioprotection with carvedilol in patients with breast cancer (CCT guide): a phase 1 randomized clinical trial.

Breast Cancer Res Treat 211(2):293-305

Authors: Wonyoung Jung, Rebecca A Hubbard, Amanda M Smith, Kyunga Ko, Anran Huang, Jessica Wang, Jordan M Isaacs, Liyong Zhang, Peter P Liu, Zhen Chen, Payal D Shah, David Mintzer, Saveri Bhattacharya, Hayley M Knollman, Amy S Clark, Daniel Koropeckyj-Cox, Melissa Messinger, Nicholas S Wilcox, Congying Xia, Vivek Narayan, Jenica N Upshaw, Saro H Armenian, Bonnie Ky

Affiliations

  • Division of Cardiology, Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
  • Department of Biostatistics, Brown University School of Public Health, Providence, RI, USA.
  • University of Ottawa Heart Institute, University of Ottawa, Ottawa, ON, Canada.
  • Division of Hematology and Oncology, Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
  • Division of Cardiology, Tufts Medical Center, Boston, MA, USA.
  • Department of Pediatrics and Department of Population Sciences, City of Hope Comprehensive Cancer Center, Duarte, CA, USA.
  • Division of Cardiology, Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
  • Abramson Cancer Center, Penn Center for Quantitative Echocardiography, Perelman School of Medicine at the University of Pennsylvania, 3400 Civic Center Boulevard, Philadelphia, PA, 19104, USA.
  • Department of Biostatistics, Epidemiology and Informatics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.

Abstract

PURPOSE

Breast cancer treatment results in increased cardiotoxicity risk; a risk-guided approach to cardioprotection has not been fully tested.

METHODS

This single-center, randomized Phase I trial enrolled patients with Stage I-III breast cancer who planned to receive anthracycline and/or trastuzumab therapy. An internally validated cardiotoxicity risk score classified participants as low or elevated risk. Elevated risk participants were randomized to receive open-label carvedilol or usual care for 12 months, beginning at cancer therapy initiation. Study visits occurred at baseline, 3, 6, 9, 12, and 24 months. Primary outcomes included feasibility, safety, and tolerability. Exploratory outcomes included echocardiography, biologic, and patient-reported measures.

RESULTS

Of the 166 eligible patients approached, 68 (41%) agreed to participate and ultimately enrolled. Among these participants (median age 52, 35% Black), 49 were classified as low and 19 elevated risk. Within the elevated risk group, 13 were randomized to carvedilol and 6 usual care. For those randomized to carvedilol, the median maximum dose was 6.25 mg twice daily, with 93% adherence. Adverse events of interest (grade 3 + bradycardia, hypotension, or fatigue) occurred in 9% with carvedilol, 13% in usual care, and 4% in low risk groups. One (1.5%) low risk participant experienced cardiac dysfunction. There were no substantial differences in secondary outcomes across groups. The participant withdrawal rate was 7%.

CONCLUSIONS

This Phase 1 trial demonstrates that a risk-guided strategy can be applied to patients with active cancer. However, additional strategies are necessary to optimize the design and execution of non-treatment intervention trials in patients with active cancer.

TRIAL REGISTRATION

NCT04023110.

MeSH

Carvedilol, Breast Neoplasms, Neoplasms, Breast, Cardiotoxicity, Therapeutics