Recent Clinical Advances: Key Trial Data in First-Line mTNBC

Recent data from a pivotal clinical trial have influenced how first-line treatment is approached for patients with PD-L1–positive mTNBC. The ASCENT-04 trial, also known as KEYNOTE-D19, evaluated previously untreated patients with PD-L1 expression (combined positive score, ≥10) who were at least 6 months out from curative treatment. Participants were randomly assigned to receive either standard chemotherapy plus pembrolizumab or sacituzumab govitecan plus pembrolizumab. The study enrolled 443 patients globally, with balanced demographics and disease characteristics across arms. Most had visceral metastases, and a minority had prior exposure to PD-1/PD-L1 therapies in earlier stages.

The trial results showed a significant improvement in progression-free survival (PFS) with sacituzumab govitecan and pembrolizumab compared with the chemotherapy combination. The median PFS was 11.2 months vs 7.8 months, respectively, with an HR of 0.65, indicating a statistically meaningful benefit. This advantage was especially notable in patients with recurrent disease, though de novo metastatic patients also showed a favorable trend. Although overall survival data remain immature, early trends favor the sacituzumab govitecan regimen. Adverse events were consistent with known profiles: neutropenia, diarrhea, and alopecia were more common in the ADC group, whereas immune-related events aligned with expectations for pembrolizumab.

Although sacituzumab govitecan is not yet approved for first-line use in mTNBC, its approval is anticipated, especially for PD-L1–positive cases. For PD-L1–negative patients—who represent about 60% of mTNBC cases—early results from the ASCENT-03 trial also suggest a PFS benefit with sacituzumab govitecan over chemotherapy, with full data expected soon. Additionally, another ADC, datopotamab deruxtecan, is under investigation in the TROPION-Breast02 trial, potentially expanding first-line options even for patients ineligible for immunotherapy. These developments highlight the growing importance of biomarker testing to guide integration of ADCs and immunotherapy in personalized treatment strategies.