TDM1, Radiation Considered Safe for Patients with Early-Stage HER2-Positive Breast Cancer

Expert sits with Pharmacy Times to share the promising results of a study that evaluated the safety of a new antibody drug conjugate with radiation therapy.

Mridula George, MD, medical oncologist in the Stacy Goldstein Breast Cancer Center at Rutgers Cancer Institute of New Jersey and RWJBarnabas Health, presented a poster of the retrospective results of a study looking at the risks of cardiotoxicity with adjuvant therapy, trastuzumab emtansine (TDM1), with adjuvant breast radiation for early-stage and HER2-positive metastatic breast cancer at the San Antonio Breast Cancer Symposium (SABCS).

PT Staff: What are some of the main takeaways about risk of cardiotoxicity with concurrent trastuzumab emtansine (TDM1) and radiation therapy in patients with early-stage HER2 positive breast cancer?

Mridula George, MD: So trastuzumab emtansine (TDM1) is one of the drugs that's used for the treatment of early-stage and metastatic HER2-positive breast cancers. HER2-positive breast cancers comprise about 15% to 20% of all the breast cancers that are diagnosed in the US and worldwide. TDM1 is an antibody drug conjugate consisting of the anti-HER2 antibody drug, trastuzumab, which is bound to an anti-microtubule agent called emtansine.

Trastuzumab, or most of the drugs that are treated or used for the treatment of HER2-positive breast cancers, is associated with the risk of cardiotoxicity, specifically a drop in left ventricular ejection fraction. And this risk is also seen with certain chemotherapy medications such as the anthracycline-based drugs. The mechanism of HER2- based cardiotoxicity is not very well understood, but it is reversible.

It causes a functional change in the cardiac myocytes, but HER2-targeted therapy is discontinued, the cardiac function does revert to its baseline. So there's also a risk of cardiac toxicity with the use of radiation. There are a lot of studies looking at radiation to the left breast versus right breast, and the risk of ischemic heart disease, especially for younger women. And studies have shown that, with women getting radiation to the left side (left breast, since the left breast is closer to the heart), there is a risk of radiation exposure to the heart and a long-term increased risk of ischemic heart disease— given the risks of cardiotoxicity seen with trastuzumab, emtansine, and radiation.

We did a retrospective review looking at patients who received concurrent trasturzumab, emtansine, and radiation to see if there was a reduced reduction in the left ventricular ejection fraction—31 patients were eligible as part of our review. Out of the 31 patients, 2 patients had a greater than 10% reduction and left ventricular ejection fraction. Both patients were asymptomatic. They did not have any adverse clinical symptoms of heart failure. So when patients are on TDM1, or any of the HER2-targeted antibody drugs, the cardiotoxicity is reversible once the drug is stopped.

Based on our study, the main takeaway was that it is safe to receive concurrent trastuzumab and emtansine with radiation in patients with HER2-positive breast cancer. However, we need to do longer studies, especially looking at the risk of ischemic heart disease in these patients, because they are getting an anti-microtubule agent with a harder targeted therapy during radiation. Those are things that we can look at in a larger study and would be much longer or follow up.

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