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ADCs for Pharmacists FAQs
Expert Answers to FAQs on HER2-, HER3-, and TROP-2–Directed ADCs for Pharmacists

Released: April 23, 2024

Expiration: April 22, 2025

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Key Takeaways
  • Although data suggest most patients will not experience recurrent interstitial lung disease (ILD), it is reasonable to monitor more closely when a patient is restarting trastuzumab deruxtecan after holding for grade 1 ILD.
  • Subsequent infusions of sacituzumab govitecan can be shortened to 1 hour if the first 3-hour infusion goes well.
  • The use of dose rounding with approved antibody–drug conjugates is an option but varies between institutions and insurance plans.

In this commentary, Allison Butts, PharmD, BCOP, and Sandra Cuellar, PharmD, BCOP, FHOPA, FASHP, answer questions posed by an audience of oncology pharmacists during a symposium titled, “Maximizing Efficacy and Minimizing Toxicity of ADCs Targeting HER2, HER3, and TROP-2: Strategies for Oncology Pharmacists.” To date, the FDA has approved 2 HER2-directed antibody–drug conjugates (ADCs), trastuzumab emtansine and trastuzumab deruxtecan, along with 1 TROP-2–directed ADC, sacituzumab govitecan. Other ADCs under review by the FDA include the HER3-directed ADC patritumab deruxtecan and the TROP-2–directed ADC datopotamab deruxtecan.

When a patient is restarting trastuzumab deruxtecan after experiencing drug-related grade 1 interstitial lung disease (ILD), do you monitor more frequently for that toxicity?

Sandra Cuellar, PharmD, BCOP, FHOPA, FASHP:
This is a good question highlighting a situation lacking both data and guidelines. In my practice, I do consider it reasonable to monitor more frequently when restarting trastuzumab deruxtecan after grade 1 ILD. We often consult a pulmonologist when faced with this scenario.

Pharmacists can also turn to a 2022 expert opinion paper published in ESMO Open on managing drug-induced ILD in patients with cancer. An Italian expert panel recommends that, 2 weeks after the patient holds therapy for grade 1 ILD, they should undergo clinical evaluation, high-resolution CT of the chest, and respiratory function tests. There are no specific recommendations on monitoring after restarting therapy. If the patient is one of the few who continue therapy without holding for a grade 1 event, the panel recommends close clinical monitoring along with high-resolution CT of the chest and respiratory function tests before each cycle. This latter recommendation strikes me as challenging from a resource standpoint.

Allison Butts, PharmD, BCOP:
I have not yet encountered this situation. I have only had 1 patient with grade 1 ILD, which was identified on the same routine staging scans that observed disease progression.

This is a difficult question and a difficult diagnosis. Even for grade ≥2 ILD, many of the symptoms are nonspecific. Fever, mild cough, and shortness of breath are important symptoms but very easy to overlook, especially if the patient has lung metastases.

Sandra Cuellar, PharmD, BCOP, FHOPA, FASHP:
I agree. Detecting asymptomatic grade 1 ILD can be particularly challenging if there is no other reason to perform imaging. Fortunately, the black box warning with trastuzumab deruxtecan does increase clinical suspicion for ILD.

A related question is, what is the likelihood that the patient will have recurrent ILD when rechallenged? A pooled analysis of 9 phase I/II studies evaluating trastuzumab deruxtecan reported that of the 47 patients who were rechallenged after grade 1 ILD, only 3 developed recurrent ILD (all grade 1). These data suggest that just because a patient develops grade 1 ILD once, they will not automatically develop ILD again with rechallenge. The decision to rechallenge ultimately depends on the individual’s risk-vs-benefit calculation.

For sacituzumab govitecan, do you shorten the administration time from 3 hours at the first infusion to 1 hour at the second, or do you shorten to 2 hours at the second and then 1 hour at the third?

Allison Butts, PharmD, BCOP:
The prescribing information recommends administering sacituzumab govitecan over 3 hours for the first infusion and, if that goes well, reducing to 1-2 hours for subsequent infusions. In my practice, we go from 3 hours at the first infusion to 1 hour at the second. None of our patients have experienced infusion reactions to sacituzumab govitecan to date. If a patient did have a reaction to the 1-hour infusion, it would be reasonable to try the 2-hour duration at the next infusion rather than increasing to 3 hours.

Sandra Cuellar, PharmD, BCOP, FHOPA, FASHP:
We also have not had any infusion reactions to sacituzumab govitecan. At my institution, we are very sensitive to “chair time” and routinely do 1-hour infusions without any safety issues.

Do you dose band or round to the nearest vial size with any of the approved ADCs?

Sandra Cuellar, PharmD, BCOP, FHOPA, FASHP:
We do not automatically dose round. However, I have had insurance companies come back and tell me I need to dose round. When that happens, I manually change our system to dose round to the amount approved by insurance.

Allison Butts, PharmD, BCOP:
We try to dose round when possible. Questions arise when insurance requires rounding down, because our system is built to dose round to vial size (which may involve rounding up to the nearest full vial size, not down).

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