People with hormone receptor (HR)-positive, HER2-negative breast cancer that has spread (metastasized) usually receive endocrine therapy as the first treatment. These breast cancers often ultimately become resistant to endocrine therapy and continue growing. At this point, doctors typically give individual chemotherapy drugs one after another, but this practice hasn’t extended survival by much, and patients can suffer severe, lasting side effects.
In recent years, a new treatment called sacituzumab govitecan-hziy (TRODELVY®) has proved effective in treating HR-positive, HER2-negative breast cancers that have progressed after endocrine therapy and standard chemotherapy have failed. Sacituzumab govitecan-hziy acts as a type of “smart bomb” that delivers a chemotherapy payload more precisely to cancer cells. It was approved by the U.S. Food and Drug Administration (FDA) in 2023 and has become a standard treatment for these patients.
Based on this success, researchers hoped sacituzumab govitecan-hziy might be effective if given earlier — as the next treatment after endocrine therapy stopped working.
Now a phase 3 clinical trial testing sacituzumab govitecan-hziy as the first treatment after endocrine therapy has shown mixed results. In the study, called ASCENT-07, sacituzumab govitecan-hziy did not appear to work better than chemotherapy in terms of slowing disease progression — the main objective of the trial.
However, there were intriguing signs suggesting that sacituzumab govitecan-hziy could lower the risk of death over time.
“These preliminary results related to survival are very interesting, and we need to continue following this closely,” says Memorial Sloan Kettering Cancer Center (MSK) medical oncologist Komal Jhaveri, MD, FACP, FASCO. “We did not see any new safety concerns giving sacituzumab govitecan-hziy earlier, which is encouraging, in addition to the fact that fewer patients stopped taking this drug compared with chemotherapy. In the meantime, sacituzumab govitecan-hziy remains an effective treatment option for patients whose cancer has progressed despite treatment with endocrine therapy and chemotherapy.”
Dr. Jhaveri presented results from ASCENT-07 at the San Antonio Breast Cancer Symposium (SABCS), held December 9-12, 2025.
This Antibody-Drug Conjugate Works by Targeting the Trop-2 Protein
Sacituzumab govitecan-hziy is a newer type of drug called an antibody-drug conjugate (ADC), which treats cancer by combining three parts:
- An antibody that binds to specific proteins or receptors on the surface of the cancer cell.
- A drug toxic to the cancer cell.
- A linker that connects the drug and antibody, keeping the drug bound to the antibody until the duo arrives at the cancer cell to destroy it.
Sacituzumab govitecan-hziy targets a protein called Trop-2, which is found on the surface of most breast cancer cells. Dr. Jhaveri and MSK played an essential role in a previous clinical trial (called TROPiCS-02) that resulted in the 2023 FDA approval for this ADC. (MSK enrolled the most patients of any institution participating in the large, international trial.)
Future of Treating HR-positive, HER2-negative Breast Cancer
HR-positive, HER2-negative breast cancer is the most common type of the disease, and it is very heterogenous — meaning its cells can have significant genetic and molecular differences. This complexity has made it especially challenging to treat, particularly in patients who have received many rounds of endocrine therapy, Dr. Jhaveri explains.
“The preliminary results from the ASCENT-07 trial suggesting a lower risk of death among patients receiving sacituzumab govitecan-hziy is a noteworthy signal — but we don’t know why it occurs or what it means,” Dr. Jhaveri says. “That’s why we need to focus on the patients in the study and follow this over the longer term. Often a trial with disappointing results teaches us something important that leads to a change in the standard of care down the road.”
Key Takeaways
- Sacituzumab govitecan-hziy (TRODELVY®) has proved effective in treating HR-positive, HER2-negative breast cancers that have progressed after endocrine therapy and standard chemotherapy have failed.
- Dr. Komal Jhaveri and MSK played an essential role in a previous clinical trial (called TROPiCS-02) that resulted in the 2023 FDA approval of sacituzumab govitecan-hziy.
- A new clinical trial tested if sacituzumab govitecan-hziy would be effective if given earlier — as the next treatment after endocrine therapy stopped working.
- Sacituzumab govitecan-hziy did not appear to work better than chemotherapy in terms of slowing disease progression, but there were intriguing signs suggesting that it could lower the risk of death over time.
- There were no new safety concerns associated with giving sacituzumab govitecan-hziy earlier.