Preventing Cardiac Damage in Patients Treated for Breast Cancer and Lymphoma: The PROACT Clinical Trial

Austin, David; Maier, Rebecca H.; Akhter, Nasima; Sayari, Mohammad; Ogundimu, Emmanuel; Maddox, Jamie M.; Vahabi, Sharareh; Humphreys, Alison C.; Graham, Janine; Oxenham, Helen; Haney, Sophie; Cresti, Nicola; Verrill, Mark; Osborne, Wendy; Wright, Kathryn L.; Goranova, Rebecca; Bailey, James R.; Kalakonda, Nagesh; Macheta, Mac; Kilner, Mari F.; Young, Moya E.; Morley, Nick J.; Neelakantan, Pratap; Gilbert, Georgia; Thomas, Byju K.; Graham, Richard J.; Fujisawa, Takeshi; Mills, Nicholas L.; Hildreth, Victoria; Prichard, Jonathan; Kasim, Adetayo S.; Hancock, Helen C.; Plummer, Chris

Abstract

Background
Cardiotoxicity is a concern for cancer survivors undergoing anthracycline chemotherapy. Enalapril has been explored for its potential to mitigate cardiotoxicity in cancer patients. The dose-dependent cardiotoxicity effects of anthracyclines can be detected early through the biomarker cardiac troponin.

Objectives
The PROACT (Preventing Cardiac Damage in Patients Treated for Breast Cancer and Lymphoma) clinical trial assessed the effectiveness of enalapril in preventing cardiotoxicity, manifesting as myocardial injury and cardiac function impairment, in patients undergoing high-dose anthracycline-based chemotherapy for breast cancer or non-Hodgkin lymphoma.

Methods
This prospective, multicenter, open-label, randomized controlled trial employed a superiority design with observer-blinded endpoints. A total of 111 participants, scheduled for 6 cycles of chemotherapy with a planned dose of≥300mg/m2 doxorubicin equivalents, were randomized to receive either enalapril (titrated up to 20mg daily) or standard care without enalapril.

Results
Myocardial injury, indicated by cardiac troponin T (≥14ng/L), during and 1month after chemotherapy, was observed in 42 (77.8%) of 54 patients in the enalapril group vs 45 (83.3%) of 54 patients in the standard care group (OR: 0.65; 95% CI: 0.23-1.78). Injury detected by cardiac troponin I (>26.2ng/L) occurred in 25 (47.2%) of 53 patients on enalapril compared with 24 (45.3%) of 53 in standard care (OR: 1.10; 95% CI: 0.50-2.38). A relative decline of more than 15% from baseline in left ventricular global longitudinal strain was observed in 10 (21.3%) of 47 patients on enalapril and 9 (21.9%) of 41 in standard care (OR: 0.95; 95% CI: 0.33-2.74). An absolute decline of >10% to<50% in left ventricular ejection fraction was seen in 2 (4.1%) of 49 patients on enalapril vs none in patients in standard care.

Conclusions
Adding enalapril to standard care during chemotherapy did not prevent cardiotoxicity in patients receiving high-dose anthracycline-based chemotherapy. (PROACT: Can we prevent Chemotherapy-related Heart Damage in Patients With Breast Cancer and Lymphoma?; NCT03265574)

Citation

Austin, D., Maier, R. H., Akhter, N., Sayari, M., Ogundimu, E., Maddox, J. M., Vahabi, S., Humphreys, A. C., Graham, J., Oxenham, H., Haney, S., Cresti, N., Verrill, M., Osborne, W., Wright, K. L., Goranova, R., Bailey, J. R., Kalakonda, N., Macheta, M., Kilner, M. F., …Plummer, C. (2024). Preventing Cardiac Damage in Patients Treated for Breast Cancer and Lymphoma: The PROACT Clinical Trial. Journal of the American College of Cardiology, 6(5), 684-696. https://doi.org/10.1016/j.jaccao.2024.07.010

• Journal Article Type: Article
• Acceptance Date: Jul 12, 2024
• Online Publication Date: Oct 15, 2024
• Publication Date: 2024-10
• Deposit Date: Oct 22, 2024
• Publicly Available Date: Oct 22, 2024
• Journal: JACC: CardioOncology
• Print ISSN: 0735-1097
• Electronic ISSN: 1558-3597
• Publisher: Elsevier
• Peer Reviewed: Peer Reviewed
• Volume: 6
• Issue: 5
• Pages: 684-696
• DOI: https://doi.org/10.1016/j.jaccao.2024.07.010
• Public URL: https://durham-repository.worktribe.com/output/2979971