Managing ADC toxicities in HER2+ metastatic breast cancer

Nausea and vomiting are among the most common and distressing adverse events associated with ADCs, particularly T-DXd in HER2-positive mBC.

Alongside these gastrointestinal toxicities, other adverse events such as fatigue and interstitial lung disease (ILD) are also of critical clinical importance. Proactive management of these toxicities is essential to maintain quality of life and ensure treatment continuity.

In this video, Dr Sara Tolaney outlines a practical approach to managing these toxicities in clinical practice, including:

• The clinical role of ADCs in HER2+ mBC
• How to classify emetogenic risk and tailor antiemetic prophylaxis accordingly
• Step-by-step guidance for managing breakthrough symptoms and adjusting treatment over time
• Additional considerations for other key toxicities, including fatigue and ILD

Watch now and download the slide deck for more information and step-by-step guidance on managing ADC-related adverse events.

Clinical takeaways

• T-DXd is a highly emetogenic agent, warranting prophylaxis with a 3-drug regimen: a 5-HT3 RA, NK1 RA, and dexamethasone. A 4-drug regimen including olanzapine is recommended if prior 3-drug prophylaxis was inadequate or for patients at high-risk (e.g. younger age, history of CINV, anxiety, hyperemesis during pregnancy).

• As breakthrough nausea and vomiting may occur despite prophylaxis—within 5 days
  (acute) or between days 6–21 (delayed) post–T-DXd—upfront prescribing of olanzapine 2.5 mg nocte is recommended for potential acute or delayed symptoms, and ondansetron 8 mg every 8–12 h (16–24 mg total daily dose) as an alternative for delayed nausea, to enable as needed use.

• Fatigue associated with T-DXd should be proactively managed through routine screening, assessment of reversible causes, patient education, supportive care, and dose adjustments when needed.

• ILD is a potentially serious adverse event with T-DXd and should be addressed using the 5S approach: Screen regularly, scan early, synergise with the patient and MDT, suspend treatment if ILD is suspected, and initiate steroids promptly if ILD is suspected.