[ASCO 2025] Trodelvy could emerge as standard of care for triple-negative breast cancer

CHICAGO, Ill.--By Kim Yun-mi/Korea Biomedical Review correspondent--The first TROP-2-targeting antibody-drug conjugate (ADC) Trodelvy (sacituzumab govitecan) has demonstrated first-line outcomes beyond conventional chemotherapy plus immuno-oncology in PD-L1-positive advanced triple-negative breast cancer (TNBC).

Trodelvy, already in third-line and beyond, recently reached a pivotal milestone that could advance it to first-line treatment and become the new standard of care for TNBC.

Results from the phase 3 ASCENT-04/KEYNOTE-D19 study evaluating Trodelvy in combination with Keytruda (pembrolizumab) in patients with PD-L1-positive advanced TNBC were presented on Friday (local time) at the American Society of Clinical Oncology 2025 Annual Meeting (ASCO 2025).

Triple-negative breast cancer accounts for about 10 percent of all breast cancers and is known to be more difficult to treat than other subtypes. Because they are negative for both hormone receptor (HR) and human epidermal growth factor receptor 2 (HER2) proteins, they are not amenable to conventional targeted therapies. Large tumor sizes and high rates of metastasis and recurrence characterize them.

The current standard of care for PD-L1-positive advanced TNBC is chemotherapy plus pembrolizumab, but even with this treatment, the three-year survival rate for patients remains low at 36 percent.

“Many patients with metastatic TNBC do not receive additional treatment after first-line therapy due to poor health or death, so there is a need for better options in the first-line setting,” said Dr. Sara M. Tolaney of Harvard Medical School, who presented the ASCENT-04/KEYNOTE-D19 study.

The study compared the combination of Trodelvy plus pembrolizumab (221 patients) to chemotherapy plus pembrolizumab (222 patients) in 443 patients with PD-L1-positive advanced TNBC from 26 countries.

Over a median follow-up of 14 months, the median progression-free survival (mPFS) in the Trodelvy arm was 11.2 months compared to 7.8 months in the control arm, a significant prolongation and a 35 percent reduction in the risk of disease progression. The median duration of response (mDOR) was also favorable in the Trodelvy arm (16.5 months vs. 9.2 months).

The most common grade 3-4 adverse events in the Trodelvy arm were neutropenia (43 percent) and diarrhea (10 percent), while the most frequent grade 3-4 adverse events in the control arm were neutropenia (45 percent), anemia (16 percent), and thrombocytopenia (14 percent).

Commenting on the results, Professor Park Kyong-hwa of the Department of Hematology-Oncology at Korea University Anam Hospital emphasized the value of the Trodelvy combination in terms of patient quality of life.

“Triple-negative breast cancer cannot be completely cured,” Professor Park said, pointing out the reality of treating triple-negative breast cancer. Current first-line treatments include taxane- or platinum-based drugs in combination with immuno-oncology drugs. Still, they are difficult to use for extended periods due to side effects such as numbness and swelling.”

It is frustrating for clinicians to have to discontinue a drug due to side effects, even though the cancer is chemotherapy-sensitive and the tumor burden continues to shrink. Park explained that Trodelvy can be used for a relatively long time before resistance develops, making it a valuable alternative in the current treatment landscape.

“While it's important to increase patient survival in first-line treatment, reducing the suffering patients endure during treatment is truly good care. Trodelvy can be a great partner in this regard,” Professor Park added.