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mTNBC Practice Readiness: Applying Current Standards and Interpreting Emerging First-line TROP2 ADC Evidence for Immunotherapy-Ineligible Patients

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This activity is available for 0.75 CME/CE credit(s).

Released: October 13, 2026

Expiration: April 12, 2027

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1 Pre Assessment 2 Video 3 Post Assessment 4 Evaluation 5 Credit

In this on-demand webcast, experts review the clinical rationale for targeting TROP2 in metastatic triple-negative breast cancer (mTNBC) and the evolving role of TROP2-directed antibody–drug conjugates (ADCs), with emphasis on first-line treatment of patients who are not candidates for immunotherapy. The faculty discuss efficacy and safety data from key randomized trials, including ASCENT-03 and TROPION-Breast02, and consider how differences in trial populations, treatment-free interval, prior therapy, comorbidities, and patient preferences may inform selection between sacituzumab govitecan and datopotamab deruxtecan. The faculty also address prevention and management of treatment-related toxicities, including neutropenia, diarrhea, stomatitis, ocular surface events, and interstitial lung disease, as well as practical strategies for supportive care and multidisciplinary monitoring. Finally, the experts explore sequencing considerations after TROP2-directed ADC therapy, the potential impact of ADC resistance mechanisms, ongoing phase III studies in early and advanced TNBC, and emerging data in patients with active brain metastases, highlighting factors that may influence individualized treatment planning across the disease course.

Thomas Bachelot
Thomas Bachelot, MD, PhD
Rupert Bartsch
Rupert Bartsch, MD
Giuseppe Curigliano
Giuseppe Curigliano, MD, PhD
1L TROP2 ADC Evidence

Pre Assessment

Assess your current knowledge and clinical approach before beginning your video.
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1.

How many people with breast cancer do you provide care for in a typical month?

2.

For those who practice in academic or community settings, please indicate your practice setting:

3.

Patient Case 1: 54-Yr-Old Woman With Stage III TNBC Who Received Neoadjuvant KEYNOTE-522 Regimen



  • A 54-yr-old woman with stage III TNBC received neoadjuvant pembrolizumab + paclitaxel and carboplatin followed by pembrolizumab + doxorubicin and cyclophosphamide (KEYNOTE-522 regimen)

  • Germline BRCA1/2 testing was negative

  • During neoadjuvant treatment, she experienced febrile neutropenia despite G-CSF support

  • She also has chronic bile-acid diarrhea following cholecystectomy, controlled with cholestyramine

  • After mastectomy revealed substantial residual disease and involved axillary lymph nodes (non-pCR), she continued adjuvant pembrolizumab with the addition of capecitabine

  • 7 mo after completing adjuvant therapy, she developed fatigue and right upper quadrant discomfort; imaging demonstrated multiple bilobar liver metastases

  • Biopsy confirmed metastatic TNBC with HER2 IHC 0 and PD-L1 CPS 6; ECOG PS 1, liver function remains preserved

  • She has no history of ILD/pneumonitis, no clinically significant corneal disease, and no stomatitis

  • Based on shared decision-making, she prioritizes rapid disease control and wishes to avoid worsening neuropathy 

Based on rapid disease recurrence while receiving pembrolizumab, the presence of liver disease, comorbidities, and patient preferences, which systemic therapy represents the preferred next treatment for this patient?

4.

Patient Case 2: 61-Yr-Old Woman Presents With Persistent Right Upper Quadrant Discomfort



  • A 61-yr-old woman presents with persistent right upper quadrant discomfort

  • Approximately 18 mo after completing curative-intent treatment for stage II HR+/HER2- breast cancer, imaging reveals multiple liver lesions and pulmonary nodules

    • Biopsy of a liver lesion confirms recurrent breast carcinoma that is ER-, PgR-, and HER2- (TNBC)

    • Loss of HR expression may reflect tumor evolution under treatment pressure, although heterogeneity and sampling variability can also contribute



  • PD-L1 testing using the 22C3 pharmDx assay shows CPS <5

  • No systemic therapy for advanced disease, ECOG PS 1, and no active CNS metastases

  • Because her tumor has a PD-L1 CPS <10, she is not a candidate for PD-1/PD-L1 inhibitor–based therapy at this time

  • The oncology team discusses evidence from the phase III ASCENT-03 trial, which evaluated 1L sacituzumab govitecan vs physician’s choice chemotherapy in this clinical setting 

In the primary analysis from the phase III ASCENT-03 trial, which of the following was reported for sacituzumab govitecan vs physician’s choice chemotherapy in patients with previously untreated, locally advanced inoperable or metastatic TNBC who were not candidates for PD-1/PD-L1 inhibitor therapy?

5.

Patient Case 3: 67-Yr-Old Woman Receiving Datopotamab Deruxtecan Who Develops Stomatitis



  • A 67-yr-old woman with PD-L1–low mTNBC initiates 1L Dato-DXd after multidisciplinary review

  • Before treatment, nursing and pharmacy recommend a steroid-containing mouth rinse 3-4 times/day, routine oral hygiene, and early symptom reporting

  • She also begins preservative-free artificial tears containing hyaluronic acid and has no baseline ocular abnormalities

  • Before cycle 2, she reports mild oral soreness and erythema without ulcers or interference with eating or drinking

  • Examination shows no thrush or other oral infection

  • She acknowledges using the steroid-containing mouth rinse only once/day

  • The team classifies the event as grade 1 stomatitis and meets to coordinate supportive care 

Based on current evidence for TROP2 ADC–based strategies in immunotherapy-ineligible mTNBC, which multidisciplinary plan is most appropriate for this patient’s grade 1 Dato-DXd–associated stomatitis?

6.

How confident are you in selecting appropriate patients for available anti-TROP2 ADCs?

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