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Managing AEs From ADC Therapy
Effective Management of Adverse Events Associated With ADC Therapy: Expert Answers to Your Questions on Nausea, Alopecia, and Cardiotoxicity

Released: December 04, 2024

Expiration: December 03, 2025

Sara Cooper
Sara Cooper, MSN, RN, ACNP-BC, AOCNP-BC
Kristi K. Orbaugh
Kristi K. Orbaugh, MSN, RNP, AOCNP
Kimberly Podsada
Kimberly Podsada, MSN, NP-C
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Key Takeaways
  • Comprehensive antiemetic strategies are essential for managing chemotherapy-induced nausea and vomiting associated with antibody–drug conjugates (ADCs) including T-DXd and sacituzumab govitecan, especially for patients with high-risk nausea histories.
  • Alopecia counseling including practical solutions and emotional support before starting ADC therapy is important to help patients navigate this challenging side effect.
  • Cardiac monitoring protocols for T-DXd should be individualized, with frequent assessments for high-risk patients to preemptively address cardiotoxicity.

Antibody–drug conjugates (ADCs) such as trastuzumab deruxtecan (T-DXd) and sacituzumab govitecan (SG) are therapeutic options for an increasing population of patients with cancer. However, as with many oncology treatments, managing associated adverse events (AEs) is critical for optimizing patient outcomes. In this commentary, we share our answers to questions posed by a live audience of healthcare professionals during a webinar covering HER2-, HER3-, and TROP2-targeted ADCs, including evidence-based approaches to managing nausea and vomiting, alopecia, and cardiac function monitoring in patients receiving ADCs.

What is your approach to managing nausea and vomiting associated with these ADCs? 

Sara Cooper, MSN, RN, ACNP-BC, AOCNP-BC:
Patients receiving T-DXd and SG commonly experience nausea and vomiting due to their moderate to high emetogenic potential. Evidence from trials like DESTINY-Breast04 indicates that nausea affects more than 70% of patients treated with T-DXd, necessitating proactive measures​​. T-DXd was initially categorized as having moderate emetogenic potential, although it appeared to be on the higher end of this
category. It has since been recategorized to high emetogenic potential. In my practice, we are actually offering patients on T-DXd a 4-drug combination regimen with an NK1 receptor antagonist, a 5-HT3 receptor antagonist, dexamethasone, and olanzapine to make sure that we are giving them proper nausea prophylaxis. With more experience, I have found that I am getting better control of the nausea and vomiting of my patients on T-DXd using the high emetic risk combination regimens recommended in the most recent ASCO Antiemetic Guidelines. For SG, we premedicate with a 2- or 3-drug regimen including dexamethasone, a 5-HT3 receptor antagonist, and an NK1 receptor antagonist. Onset of nausea and vomiting may be delayed with SG, so it is important to educate patients about this and to provide them with a prescription for antiemetics to have at home.

Kimberly Podsada, MSN, NP-C:
We also generally use a 4-drug regimen for patients receiving T-DXd and have found that nausea tends to decrease over time. For breakthrough nausea, agents like ondansetron, prochlorperazine, or lorazepam are typically prescribed. Based on the patient’s symptom severity I will also prescribe low-dose olanzapine. Educating patients to recognize early signs of breakthrough nausea and ensuring access to as-needed antiemetics is important for maintaining quality of life and adherence​​.

Kristi K. Orbaugh, MSN, RNP, AOCNP:
Special attention should be given to patients with a history of severe nausea during pregnancy or motion sickness. These histories can act as predictors for heightened sensitivity to chemotherapy-induced nausea and vomiting​. Asking about such histories can help us tailor patient education and prophylactic antiemetic strategies more effectively.

How do you prepare patients for alopecia associated with ADCs?

Sara Cooper, MSN, RN, ACNP-BC, AOCNP-BC:
Alopecia is a common side effect of ADC therapies, including T-DXd and SG. In the DESTINY-Breast trials with T-DXd, alopecia was noted in approximately 34% of patients; in trials with SG, alopecia was reported in approximately 45% of patients​. Similarly, alopecia has been reported for the novel ADCs datopotamab deruxtecan (36%) and patritumab deruxtecan (25%) that are under regulatory review for potential approval.

I have learned that during pretreatment consultations, it is essential to frame the possibility of alopecia in realistic terms. Although it may manifest as thinning (grade 1) or complete loss (grade 2), both can significantly impact a patient’s self-image. Patients should be informed that alopecia is a potential outcome, even though individual responses vary.

Kristi K. Orbaugh, MSN, RNP, AOCNP:
Before starting treatment, I always have a discussion with patients about the risks of alopecia and how scarves and hats may be helpful. In addition, offering prescriptions for wigs or providing referrals to local hair loss support resources can help patients prepare psychologically and practically.

Kimberly Podsada, MSN, NP-C:
Our practice is similar. We and others may not notice a patient who is experiencing hair thinning, but it is really about what the patient is noticing, saying, and feeling that is important. I always educate my patients about the risks of alopecia and discuss their personal comfort level to prepare them.

Sara Cooper, MSN, RN, ACNP-BC, AOCNP-BC:
Do you discuss cold capping with your patients before they start treatment with an ADC? I did a literature search on this recently, and I could not find any definitive evidence supporting a benefit of cold capping in ADC-treated patients. So, I do educate my patients and tell them that they can try, but in terms of asking them to put forth the cost and the time, I don't encourage patients to cold cap.

Kimberly Podsada, MSN, NP-C:
In the metastatic disease setting, I think it is more challenging because they are on ADC therapy for as long as it is working.  So cold capping does become very expensive, though at some point with Paxman scalp cooling, patients meet the deductible. I don’t know if this applies to cold caps. With cold capping the patient has paid all this money, may still have their hair thinning and then it is just a matter of patient’s preference, whether they want to keep doing it or not.

Kristi K. Orbaugh, MSN, RNP, AOCNP:
In our practice, we do not encourage or discourage cold capping. However, it does add an extra logistical challenge for our patients who need to bring someone with them to our clinic to apply the cold caps.

How do you monitor and manage cardiac function in patients on T-DXd therapy?

Sara Cooper, MSN, RN, ACNP-BC, AOCNP-BC:
HER2-targeted therapies, including T-DXd, are associated with a risk of cardiotoxicity, particularly left ventricular dysfunction. Regular monitoring and proactive management are paramount to minimize long-term cardiac risks. Before initiating T-DXd, a thorough cardiac evaluation including baseline echocardiography or MUGA scan should be performed. For patients at high risk—those with a history of anthracycline use or pre-existing cardiac conditions—baseline biomarkers like troponin and BNP can provide additional insights​.

Kimberly Podsada, MSN, NP-C:
In our practice, we obtain a baseline echocardiogram and then repeat cardiac assessments every 3 to 4 months during the first 1 or 2 years of therapy and then at 6-month intervals for stable patients. Clinicians should remain vigilant for symptoms of heart failure, including dyspnea, fatigue, or unexplained weight gain​. Cardiac symptoms or significant drops in ejection fraction should prompt immediate dose adjustments or therapy discontinuation. Collaboration with a cardiologist for specialized management, including cardioprotective agents, ensures comprehensive care.

Your Thoughts?
What strategies have you found effective in managing nausea or alopecia in ADC-treated patients? How do you engage with cardiology colleagues in monitoring cardiac function for these therapies? Share your insights to foster collaborative learning.

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In your practice, how do you routinely give chemotherapy-induced nausea and vomiting prophylaxis for patients starting T-DXd?

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