Dr Graham on the Evaluation of RAGE Inhibition for Therapy-Related Cardiotoxicity in Breast Cancer

Deena Mary Atieh Graham, MD, gynecologic medical oncology, breast medical oncologist, John Theurer Cancer Center, Hackensack University Medical Center, discusses the rationale and objectives of a phase 1/2 pilot study (NCT05256745) evaluating RAGE inhibition to reduce cancer therapy–related cardiotoxicity in women with early-stage breast cancer.

Graham explains that this study aims to investigate the potential role the RAGE inhibitor azeliragon in mitigating long-term cardiac toxicity associated with certain chemotherapeutic regimens for patients with breast cancer. Although providing patients with effective cancer treatment remains a crucial goal, promoting long-term quality of life and survivorship is important for patients with breast cancer, she explains.

Graham and colleagues presented a posted on this trial in progress at the 2024 ASCO Annual Meeting. The primary objectives of the study are to assess changes in high-sensitivity troponin levels—a biomarker for cardiac injury—before and during treatment with azeliragon, and to evaluate the safety and tolerability of this agent when given with standard chemotherapy. Pharmacokinetics and bioavailability of the chemotherapeutic agents in combination with the RAGE inhibitor are also being analyzed.

Investigators aim to enroll 24 patients, and 8 had already been enrolled as of the May 20, 2024. Seven patients had completed treatment, two were actively receiving treatment, and one was in screening.

Graham explains that chemotherapy regimens administered to patients in the study were selected by the patients’ oncologists, and they included commonly used protocols such as doxorubicin plus cyclophosphamide, docetaxel in combination with carboplatin, trastuzumab (Herceptin), and pertuzumab (Perjeta), and docetaxel plus cyclophosphamide. Some patients also received dose-dense paclitaxel.

The RAGE inhibitor is being administered during later chemotherapy cycles, and patients are then monitored closely, Graham continues. The primary hope for this study is that RAGE inhibition will prove to be a safe strategy that does not alter the bioavailability of the chemotherapeutic agents, thereby setting the foundation for future research into cardioprotective strategies in breast cancer treatment, Graham concludes.