ASCO 2025: Sacituzumab govitecan shows superiority over standard of care for PD-L1 positive TNBC
Combination therapy of sacituzumab govitecan and pembrolizumab improves progression-free survival in metastatic PD-L1- positive TNBC patients.
Data from the ASCENT-04/KEYNOTE-D19 Phase III trial – presented at the American Society of Clinical Oncology (ASCO) Annual Meeting (30 May – 3 June; IL, USA) – reveals the superiority of combining sacituzumab govitecan and pembrolizumab as a first-line treatment option for metastatic triple-negative breast cancer (TNBC) over the current standard of care. This combination therapy offers patients within this population the opportunity to live longer without cancer progression, helping to address an unmet need in first-line treatment options.
In the USA, approximately 10% of breast cancers are triple negative – a subtype which is notoriously difficult to treat due to large tumor sizes, high rates of recurrence and lack of common biomarkers that typically guide treatment decisions. Within this subtype, about 40% of tumors express the programmed death ligand 1 (PD-L1) protein. For these patients, the current standard of care is chemotherapy with pembrolizumab; however, survival rates remain low, with only 36% of patients living beyond 3 years.
Sacituzumab govitecan, an antibody–drug conjugate, is already approved by the US FDA as a third-line treatment option for unresectable, locally advanced and metastatic TNBC. However, whether patients would benefit from this antibody–drug conjugate earlier in the treatment pathway has yet to be determined.
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“A significant portion of patients with metastatic triple-negative breast cancer do not receive treatment beyond the first-line setting for various reasons, including a decline in their health or death, demonstrating an unmet need for first-line treatment options,” commented first author Sara Tolaney (Dana-Farber Cancer Institute, Boston, Massachusetts).
Now, results of the first Phase III trial designed to study sacituzumab govitecan paired with checkpoint inhibition as a first-line treatment for PD-L1 TNBC patients have been revealed. This study enrolled 443 patients with metastatic TNBC from 26 countries, who were randomly assigned to receive either sacituzumab govitecan and pembrolizumab (221 patients) or chemotherapy and pembrolizumab (222 patients). The primary endpoint of the trial was progression-free survival or until the treatment needed to be stopped due to adverse side effects.
The results demonstrated that patients receiving both sacituzumab govitecan and pembrolizumab achieved a progression-free survival of 11.2 months compared to 7.8 months in those receiving standard chemotherapy with pembrolizumab. This represents a significant clinical benefit, with patients in the sacituzumab govitecan combination group experiencing a 35% lower risk of cancer progression than those in the standard-of-care arm. The duration of treatment response was also increased in the sacituzumab govitecan and pembrolizumab combination group, with a median duration of response being 16.5 months versus 9.2 months for patients receiving chemotherapy plus pembrolizumab.
“These findings build on the proven efficacy of sacituzumab govitecan alone later in treatment, and sacituzumab govitecan plus pembrolizumab will likely become a new front-line standard of care in this setting,” stated Jane Lowe Meisel (ASCO Expert in breast cancer).
The next steps for this study will be to continue follow-up of these patients to better understand the overall survival benefit of sacituzumab govitecan and pembrolizumab treatment compared to the standard of care.