Trodelvy with Pembrolizumab as First-Line Treatment for PD-L1-Positive Metastatic Triple-Negative Breast Cancer: ASCENT-04 Results
Compelling data have emerged regarding first-line treatment of PD-L1-positive metastatic triple-negative breast cancer. In the phase III ASCENT-04/KEYNOTE-D19 study, the combination of Trodelvy with pembrolizumab showed better results than standard chemotherapy with pembrolizumab in previously untreated patients with locally advanced unresectable or metastatic disease. The NEJM publication reports that 443 patients were enrolled.
The ASCENT-04/KEYNOTE-D19 Study
The primary finding concerns progression-free survival. Median PFS was 11.2 months in the Trodelvy plus pembrolizumab group versus 7.8 months in the chemotherapy + pembrolizumab group. This corresponded to a 35% reduction in the risk of progression or death (HR 0.65; p<0.001). The objective response rate was higher: 60% versus 53%. Duration of response was also longer — median 16.5 versus 9.2 months.
Importantly, the tolerability data appear applicable to everyday clinical practice. Grade 3 or higher adverse events occurred at roughly similar rates in both groups (71% vs 70%), but treatment discontinuation due to toxicity was notably lower with the Trodelvy plus pembrolizumab combination (12% vs 31%). Overall survival data were still immature at the time of publication.
There is another important nuance. This combination has already been included in the NCCN guidelines as a preferred regimen for first-line treatment in patients with PD-L1-positive tumors, and in the February 2026 update was designated as category 1, i.e., a preferred option at CPS ≥10.
When to Seek a Second Opinion
A repeat consultation is particularly warranted if you have metastatic triple-negative breast cancer and:
- you need to choose a first-line treatment
- the tumor is PD-L1-positive, but the treatment approach remains unclear
- you are being offered several different regimens
- you want to understand how current your proposed treatment plan is
- it is important to evaluate not just the next step but the entire further treatment sequence
What to Prepare Before Your Consultation
For the review to be truly useful, it is best to prepare in advance the histopathology report, immunohistochemistry results, PD-L1 with CPS value, discharge summaries from prior treatment (if any), and recent CT, MRI, or PET-CT. For choosing first-line treatment, the details matter. They determine how applicable the results of a major study are to a specific clinical situation.
Conclusion
ASCENT-04/KEYNOTE-D19 showed that the combination of Trodelvy with pembrolizumab can significantly improve first-line outcomes in patients with PD-L1-positive metastatic triple-negative breast cancer. For the patient, the meaning of this news comes down to one thing — today it is especially important not just to start treatment quickly, but to start it correctly, with accurate assessment of tumor biology and the logic of the entire therapy going forward.
Frequently Asked Questions
What is Trodelvy for triple-negative breast cancer?
Trodelvy, or sacituzumab govitecan, is a TROP-2-directed antibody-drug conjugate. In the ASCENT-04 study, it was evaluated in combination with pembrolizumab as first-line treatment for PD-L1-positive advanced triple-negative breast cancer.
What results did the Trodelvy plus pembrolizumab combination show?
In the study, median PFS was 11.2 months versus 7.8 months with standard chemotherapy plus pembrolizumab. The response rate was 60% versus 53%, and the duration of response was 16.5 months versus 9.2 months.
Who might be eligible for this regimen?
The study included previously untreated patients with unresectable locally advanced or metastatic triple-negative breast cancer and PD-L1-positive tumors. NCCN separately notes the CPS ≥10 threshold.
More answers on the FAQ page.