Metastatic triple-negative breast cancer (TNBC) remains one of the most difficult breast cancer subtypes to treat, with limited durable responses to standard therapies. New phase III data from the ASCENT-04/KEYNOTE-D19 trial, published in the New England Journal of Medicine, show that combining sacituzumab govitecan with pembrolizumab improves outcomes compared with chemotherapy-based regimens in patients with PD-L1–positive metastatic TNBC.
The global study evaluated first-line treatment in patients with unresectable or metastatic disease, comparing the antibody–drug conjugate plus checkpoint inhibitor with standard chemotherapy plus pembrolizumab.
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Patients receiving sacituzumab govitecan with pembrolizumab achieved significantly longer progression-free survival and higher response rates than those treated with chemotherapy plus immunotherapy. Responses were more durable, and early overall survival trends favoured the experimental combination.
Median progression-free survival was 11.2 months with sacituzumab govitecan plus pembrolizumab compared with 7.8 months with chemotherapy plus pembrolizumab (hazard ratio 0.65; p<0.001). The objective response rate was higher with the antibody–drug conjugate combination (60% vs 53%), and the median duration of response was longer (16.5 months vs 9.2 months), while overall survival data remained immature at the time of analysis.
Safety was consistent with the known profiles of each agent, with neutropenia and gastrointestinal toxicity more frequent in the sacituzumab arm but manageable with dose modification and supportive care.
These results position Trodelvy plus pembrolizumab as a potential new first-line standard for PD-L1–positive metastatic TNBC, offering an alternative to chemotherapy-based regimens. The study also reinforces the growing role of antibody–drug conjugates as partners for immunotherapy, rather than as salvage treatments later in the disease course.
For clinicians, the data suggest a shift toward earlier use of targeted cytotoxic delivery combined with immune activation in biologically aggressive breast cancer.
Paper: Tolaney SM, et al. Sacituzumab Govitecan plus Pembrolizumab for Advanced Triple-Negative Breast Cancer. N Engl J Med. 2026 Jan 22;394(4):354-366. doi: 10.1056/NEJMoa2508959. PMID: 41564397. Access online here.
