Advancing TROP-2- Directed Antibody-Drug Conjugate Therapy in the Clinic: Applying Trial Data in Real-World Practice
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EL is a 68-year-old woman with metastatic PD-L1 TNBC (HER2 IHC = 0) and has disease progression on carboplatin/gemcitabine/pembrolizumab. Based on current options available and recent data, what would you recommend next for this patient in the 2nd line setting?

Trastuzumab deruxtecan (T-DXd)

Datopotamab deruxtecan (Dato-DxD)

Sacituzumab govitecan (SG)

Eribulin

Unsure

Anna is a 45-year-old Black woman with PD-L1 negative TNBC (HER2 IHC = 0) who has previously progressed on carboplatin; a recent CT scan showed disease progression including brain involvement. Based on her clinical profile, which treatment approach aligns best with current evidence for managing this patient?

Sacituzumab govitecan (SG), due to its efficacy in high-risk TNBC patients such as Anna

Trastuzumab deruxtecan (T-DXd) due to its broad activity in HER2-low breast cancers

An immune checkpoint inhibitor, given positive data in breast cancer patients with brain metastases

Single-agent chemotherapy, as ADCs lack evidence in breast cancer patients with brain metastases

Unsure

Maria, a 56-year-old woman with HR positive, HER2-low metastatic breast cancer has disease progression on multiple prior endocrine-based therapies and two lines of chemotherapy. Her oncologist is considering treatment with a TROP-2-directed ADC but is unsure if Maria should undergo Trop-2 expression testing first. What would be the most appropriate step?

Initiate TROP-2 ADC therapy, but only if TROP-2 expression is confirmed in Maria’s tumor biopsy.

Offer a HER2-directed ADC instead, as HER2-low status may indicate better response with HER2-targeted treatments.

Perform TROP-2 testing to determine eligibility, as TROP-2 expression must be confirmed before initiating TROP-2 ADC therapy.

Initiate TROP-2 ADC therapy without TROP-2 expression testing, as TROP-2 is commonly expressed across breast cancer subtypes.

Jenny is a 43-year-old female who recently placed on a TROP-2 ADC for metastatic HR+/HER2- breast cancer, but on cycle 2, day 1 she develops grade 3 neutropenia. What would be the next best step?

Permanently discontinue the ADC

Hold ADC and initiate granulocyte colony stimulating factor (G-CSF)

25% dose reduction and initiate G-CSF

50% dose reduction and initiate G-CSF

Evaluate UGT1A1 status

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