Trodelvy and Keytruda as First Treatment for Metastatic TNBC: A New Standard of Care?
Published on May 31, 2025
The combination of Trodelvy (chemical name: sacituzumab govitecan-hziy) and Keytruda (chemical name: pembrolizumab) as a first treatment for metastatic PD-L1-positive, triple-negative breast cancer led to longer progression-free survival than Keytruda and chemotherapy, which is the current standard of care.
Progression-free survival is how long someone lives without the cancer growing.
The results from the ASCENT-04/KEYNOTE-D19 study were presented at the 2025 American Society of Clinical Oncology Annual Meeting (ASCO).
Key takeaways
After about 14 months, progression-free survival was 11.2 months for people who received Trodelvy and Keytruda, compared to 7.8 months for people who received chemotherapy and Keytruda.
Overall survival is still being measured, but there was also a trend toward better overall survival with the Trodelvy and Keytruda combination.
Cancers responded for a longer time to Trodelvy and Keytruda (16.5 months) than they did to chemotherapy and Keytruda (9 months).
What the results mean for you
Both Trodelvy and Keytruda are approved to treat metastatic PD-L1-positive, triple-negative breast cancer, but the combination of the two medicines isn’t approved. If you’ve been diagnosed with this type of breast cancer and are deciding on first treatments, you may want to ask your doctor about these results and what they might mean for your care.
Why do the study
Although chemotherapy and Keytruda (an immunotherapy medicine) is the standard of care as a first treatment for metastatic PD-L1-positive, triple-negative breast cancer, most cancers stop responding to this combination and grow during treatment. Previous studies show that this usually happens after about 7.5 to 10 months with this treatment.
Researchers wanted to build on early research that suggested that combining immunotherapy with an antibody-drug conjugate, like Trodelvy, can treat cancer better than immunotherapy and chemotherapy.
About the study
The study included 443 people from 26 countries diagnosed with metastatic PD-L1-positive, triple-negative breast cancer that hadn’t been treated yet.
The people were randomly assigned to receive one of two treatments:
221 people received Trodelvy and Keytruda; Trodelvy was given on days one and eight of a 21-cycle and Keytruda was given on day one of a 21-day cycle
222 people received chemotherapy and Keytruda; chemotherapy medicines were Taxol (chemical name: paclitaxel) or Abraxane (chemical name: nab-paclitaxel), or a combination of Gemzar (chemical name: gemcitabine) and carboplatin
The people continued treatment until the cancer grew or they developed unacceptable side effects.
Follow-up time was about 14 months.
Detailed results
After 12 months, 48% of the people who received Trodelvy and Keytruda were alive without the cancer growing, compared to 33% of the people who received chemotherapy and Keytruda. People who received Trodelvy had a 35% lower risk of the cancer growing than people who received chemotherapy.
Among people who received Trodelvy and Keytruda, the most common severe side effects were low white blood cell counts (43%) and diarrhea (10%). Among people who received chemotherapy and Keytruda, low white blood cell counts (45%), anemia (16%), and low platelet levels (14%), which can cause bleeding and bruising problems, were the most common severe side effects.
While Trodelvy and Keytruda caused severe side effects in more people than chemotherapy and Keytruda (28% vs. 19%), fewer people had to take a lower dose (35% vs. 44%) or stop treatment (12% vs. 31%).
Lead author Sara Tolaney, MD, MPH, chief of the Division of Breast Oncology at the Dana-Farber Cancer Institute and associate professor of medicine at Harvard Medical School, presented the research at a media briefing before the ASCO Annual Meeting. “Results from [this study],” she said, “support the use of [Trodelvy] and [Keytruda] as a potential new standard of care for patients with previously untreated, PD-L1-positive, metastatic triple-negative breast cancer.”
Tolaney, S. et al. Primary Results From the Randomized, Phase 3 ASCENT-04/KEYNOTE-D19 STudy: Sacituzumab Govitecan Plus Pembrolizumab vs Chemotherapy Plus Pembrolizumab in Patients With Previously Untreated, PD-L1+, Advanced or Metastatic Triple-Negative Breast Cancer (mTNBC). 2025 ASCO Annual Meeting. Abstract LBA109.
This content is made possible by Lilly.