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FAQs on ADCs in Breast Cancer
Antibody–Drug Conjugates in Breast Cancer: Answers to Your FAQs

Released: April 28, 2025

Expiration: April 27, 2026

Elizabeth Diaz
Elizabeth Diaz, PA-C
Julia LaBarbera
Julia LaBarbera, MSN, RN, AGACNP-BC
Kimberly Podsada
Kimberly Podsada, MSN, NP-C, CNS
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Key Takeaways
  • Premedication of patients with atropine is not standard of care with sacituzumab govitecan infusion.
  • The incidence of interstitial lung disease varies with the specific ADC: approximately 12% with trastuzumab deruxtecan, 4% with datopotamab deruxtecan (Dato-DXd), 1% to 2% with trastuzumab emtansine, and not seen with sacituzumab govitecan.
  • Preservative-free eye drops, not steroid-containing eye drops, are appropriate and recommended as prophylaxis for ocular toxicities associated with Dato-DXd.

Introduction
At a recent live webinar, Elizabeth Diaz, PA-C; Julia LaBarbera, MSN, RN, AGACNP-BC; and Kimberly Podsada, MSN, NP-C, CNS addressed questions from the audience regarding the use of currently approved antibody–drug conjugates (ADCs), including trastuzumab deruxtecan (T-DXd), datopotamab deruxtecan (Dato-DXd), sacituzumab govitecan (SG), and trastuzumab emtansine (T-DM1), in the management of patients with breast cancer. This commentary summarizes their answers to the most clinically relevant audience questions.

Do you test for UGT1A1 polymorphisms in patients starting SG?

Kimberly Podsada, MSN, NP-C, CNS:
No, I do not test for UGT1A1 polymorphisms in patients starting SG. Because the frequency of this polymorphism is low, typically patients are not tested in advance. For context, patients who are homozygous or heterozygous for the UGT1A1*28 allele are at increased risk for neutropenia, febrile neutropenia, and anemia from SG compared with patients who are wild type.

Julia LaBarbera, MSN, RN, AGACNP-BC:  
I do not test for these polymorphisms in patients starting SG either. My institution follows the same policy.

Should atropine be given as premedication for all patients infused with SG? 

Elizabeth Diaz, PA-C:
We do not give atropine as a premedication for SG at our institution. However, if patients are experiencing abdominal cramping or diarrhea during the infusion, or if they return to the clinic within 48 hours of the infusion with severe symptoms, I add atropine to the next infusion of SG. I estimate approximately 20% of my patients receiving SG may need atropine because of gastrointestinal symptoms.

Julia LaBarbera, MSN, RN, AGACNP-BC:
Atropine was not given prophylactically in clinical trials with SG, so it is not something typically given at our institution either. However, some healthcare professionals (HCPs) are beginning to use atropine more often prophylactically under the assumption that it does not harm patients.

Why does the risk of interstitial lung disease (ILD) vary so widely among ADCs?

Elizabeth Diaz, PA-C:
I suspect that differences in ILD incidence with the ADCs are mainly because of the overall drug composition. There is a higher rate of ILD with T-DXd (approximately 12%) compared with Dato-DXd (approximately 4%), and ILD is really not observed with SG. Although T-DM1 is another HER2-directed ADC using trastuzumab, the rate of ILD is very low (approximately 1% or 2%). The payload (an exatecan derivative) and cleavable linker of T-DXd likely contribute to this difference, as it is a very potent drug. Other factors, such as patient risk factors (eg, prior respiratory disease, chronic obstructive pulmonary disease, and smoking status/history) could also contribute.

Julia LaBarbera, MSN, RN, AGACNP-BC:
To the best of my understanding, these differences with ILD incidence among the ADCs seem to be related to the off-target effects of these ADCs because they are observed not only with HER2-directed ADCs but also with Dato-DXd and other TROP-2–directed therapies. We should learn more about these effects as more data are obtained.

Does your institution use steroid eye drops as prophylaxis for ocular toxicities observed with Dato-DXd?

Julia LaBarbera, MSN, RN, AGACNP-BC:
Our institution does not use steroid eye drops as prophylaxis for ocular toxicities associated with Dato-DXd. We use preservative-free eye drops as often as needed by the patient. If we begin to observe keratitis, eye pain, or discomfort, we do start steroid eye drops, although they were not indicated as prophylaxis in clinical trials.

My institution follows the TROPION study guidelines for patients receiving Dato-DXd. We do a baseline ophthalmology exam, annually while receiving treatment, and at the end of treatment. We tell patients to report any change in vision or eye symptoms (dry eye, redness, eye pain, etc). I also assess for these symptoms at each follow-up visit. I advise follow-up with the ophthalmologist with any change from the patient’s baseline.

Elizabeth Diaz, PA-C:
At our institution, we also recommend lubricant eye drops and not steroid eye drops as prophylaxis for ocular toxicities associated with Dato-DXd unless the patient develops keratitis or another toxicity.

If symptoms resolve after ADC dose reduction, would an increase back to the previous dose level be appropriate?

Julia LaBarbera, MSN, RN, AGACNP-BC:
Typically, with any dose reduction, one does not go back to the starting dose because of concerns for safety, but this is really a discussion between the patient and HCP. I consider this on a case-by-case basis after weighing the benefits and risks of administering more drug with the potential to cause the same toxicity or any new toxicity. The typical recommendation does not involve reescalating the ADC after dose reduction.

Kimberly Podsada, MSN, NP-C, CNS:
I agree that HCPs should view these dosing decisions as a balancing act between effective treatment and patient quality of life. Current data support that dose reductions of ADCs maintain efficacy while improving tolerability. In my practice, we do not re-escalate back to the previous dose level of the ADC if we have previously reduced the dose for a patient.

Elizabeth Diaz, PA-C:
I agree. We usually do not reescalate drug dosing because of the risk for increasing severe toxicity and cumulative toxicity. I might consider a dose reescalation with an oral therapy where the dose could be quickly lowered.

Your Thoughts
What other strategies do you use to mitigate adverse events with ADCs in your patients with breast cancer? Join the discussion by posting a comment below.

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