Antibody Drug Conjugates in the Treatment of Endocrine-Resistant HR+/HER2- mBC


Key opinion leaders review the use of antibody-drug conjugates (ADCs) in treating HR+/HER2- metastatic breast cancer, and how they counsel patients before starting them on therapy with an ADC.

Virginia Kaklamani, MD: So, you mentioned antibody drug conjugates and you mentioned trastuzumab deruxtecan. Can you tell me a little bit about the use of trastuzumab? When do we want to use it, and what do we counsel our patients about when they are considering taking this medication?

Elizabeth Diaz, PA-C: Usually, if they fail at least one prior systemic line of chemotherapy, we consider this medication. Nausea and vomiting can be really difficult to manage. We make sure that we are using a good antiemetic regimen that's going to have two or three agents before chemotherapy. In our practice, we use a lot of olanzapine, perhaps after treatment. That's helpful, and we make sure they know to reach out to the clinic if they need IV hydration or if they need support.

Virginia Kaklamani, MD: That's extremely important. When we talk about trastuzumab deruxtecan, we often think of interstitial lung disease as a major side effect. It is a potentially serious adverse event. However, the primary side effect from TDXD is nausea and vomiting, as you mentioned. Interstitial lung disease will occur in 10% to 15% of patients. Some may be asymptomatic, or grade 1, which may be identified while we are conducting imaging. Imaging is indicated every 6 weeks for these patients, although we typically don't adhere to this in clinical practice. If we can identify interstitial lung disease at grade 1 and it is asymptomatic, then we can pause the medication and wait for it to resolve. We can also administer corticosteroids and then rechallenge the patients with TDXD. If patients exhibit symptomatic interstitial lung disease, which is grade 2 or higher, we unfortunately have to permanently discontinue TDXD and may also consider corticosteroids, a pulmonary consultation, and so forth. About 10% to 15% of patients will exhibit some degree of mild side effects with trastuzumab deruxtecan.

Let's move on to our second antibody drug conjugate (ADC), which has been approved for triple-negative breast cancer and, most recently, for HER2-positive breast cancer. This ADC, sacituzumab govitecan, can also be used in bladder cancer. How do you counsel your patients when you want to administer this ADC to them?

Elizabeth Diaz, PA-C: The primary side effects with this ADC are neutropenia and diarrhea. In our practice, we often provide growth factor support upfront to mitigate severe neutropenia and to avoid treatment delays or dose reductions. For diarrhea, I advise patients to have loperamide on hand before they even start the drug. Although antiemetics are routinely prescribed, loperamide can be purchased over-the-counter and can make a significant difference if administered early. Hair loss is another potential side effect, which can be emotionally taxing for patients. Despite this, the drug is generally well-tolerated, and we have seen success in treating both breast and bladder cancers.

Virginia Kaklamani, MD: The target of sacituzumab govitecan is TROP-2. Until this drug entered the market, TROP-2 was relatively unknown. It serves as a calcium signal transducer and is present on the surface of cancer cells. Clinical trials have not shown efficacy to be based on TROP-2 levels; therefore, we don't need to test for them. As long as patients have either HER2-positive or triple-negative breast cancer, there is a good likelihood of TROP-2 expression, making them suitable candidates for this ADC. The cytotoxic component of this ADC is SN-38, which is also the active metabolite of irinotecan. So, in a way, administering this ADC is akin to giving irinotecan to breast cancer patients, but in a more refined and targeted manner.

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