Topics:
HER2+Stage IVCardiotoxicity
Prospective Evaluation of Carvedilol vs No treatment in Prevention of Cardiac Dysfunction in Women with Metastatic HER-2+ Breast Cancer.
About this trial
- Randomized Phase III trial
- Evaluates whether prophylactic beta blocker therapy reduces the risk of cardiac dysfunction in patients with metastatic breast cancer receiving trastuzumab–based HER-2 targeted therapy
Why this trial is important
- Up to 25% of patients on trastuzumab develop cardiac dysfunction leading to interruption or discontinuation of therapy.
- Discontinuation leads to a 4-fold decrease in survival
- Preventative strategies may maximize patients’ ability to receive indefinite HER-2 targeted therapy and improve survival
Who qualifies
- Patients with metastatic breast cancer initiating OR currently on trastuzumab–based HER-2 targeted therapy without concurrent anthracyclines in the first or second line setting.
- There is no limit for number of doses of HER-2 targeted therapy prior to registration
- Patients must be at increased risk for cardiotoxicity defined by at least one of the following:
- Previous anthracycline exposure OR
- 1 or more of the following risk factors for heart disease:
- LVEF 50-54% by local ECHO read
- Age≥65
- BMI ≥ 30 kg/m2
- Current or prior anti-hypertensive therapy
- Diagnosis of coronary artery disease (CAD)
- Diabetes Mellitus
- Atrial fibrillation/flutter
Frequently asked questions (FAQ) about this trial:
What type of credentialing is required?
Echo lab credentialing requires transmission of 2 echos from any patients who have ever had breast cancer to the core lab at the University of Michigan.
Why is a central echo lab required?
- To minimize the potential for bias of the interpreting cardiologist, who may have clinical information about the patient
- Recent data from the PREDICT and SUNCOAST studies suggest high institutional “overcall” of LVEF changes at the lower end of normal ranges
Is this a placebo-controlled trial?
No.
How is the study drug paid for?
Study provides $100 and carvedilol is on the $4 list at Walmart.
Are patients already on anti-hypertensive drugs excluded?
No, patients on ARB, ACE inhibitors, or any beta blocker can be enrolled in an observational “third arm” of the study and followed in the same manner as the patients in the randomized study groups.
Why was carvedilol chosen as the study drug?
- Carvedilol is associated with antioxidant effects that may be protective against cardiac mitochondrial toxicity, lipid peroxidation, and apoptosis.
- Retrospective study of women with HER-2+ breast cancer suggested less cardiac dysfunction (12% vs 5%) with beta blocker continually during chemotherapy
- A small randomized trial of carvedilol vs placebo in patients receiving anthracyclines showed a smaller decline in mean LVEF was observed in those randomized to carvedilol.
How should I explain S1501 to a patient?
Women with Stage IV HER-2 positive breast cancer live longer if they receive and continue to receive HER-2 targeted drugs. Unfortunately, depending on baseline risk factors, up to a quarter or more of women receiving Herceptin with or without other targeted HER-2 drugs will develop heart damage that leads to stopping treatment. Because women with metastatic cancer who continue Herceptin after first progression have a 4-fold increase in survival compared to those who stop the drug, we are trying to figure out how to maximize patients’ ability to receive HER-2 targeted drugs for as long as possible. Participation in this trial may allow you to maintain treatment with HER-2 targeted drugs longer and will provide future physicians and patients with information to help design future studies aimed at maximizing safe delivery of life-saving and life-prolonging HER-2 targeted drugs.
Does the cardiologist need to be a SWOG or NCORP investigator?
No.
About the PI (Justin D. Floyd, DO)
Dr. Justin Floyd is a medical oncologist with Cancer Care Specialists of Illinois and a member of the SWOG Cancer Care Delivery Research Committee. He is board certified in Medical Oncology, as well as Hospice and Palliative Medicine. Dr. Floyd also has a special interest in toxicities of chemotherapy, non-Hodgkin’s lymphoma, and male breast cancer.
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