Combination Therapy Shows Promise in Treating Triple-Negative Breast Cancer

Introduction

Recent findings from an international phase III clinical trial, dubbed ASCENT-04/KEYNOTE-D19, indicate a significant advance in the treatment of unresectable, locally advanced or metastatic PD-L1–positive triple-negative breast cancer. Combining sacituzumab govitecan-hziy and pembrolizumab has demonstrated a substantial benefit in progression-free survival compared to the traditional chemotherapy regimen alongside pembrolizumab. These compelling results are set to be presented at the upcoming 2025 ASCO Annual Meeting.

Background of the Study

Lead researcher Dr. Sara M. Tolaney, Chief of the Division of Breast Oncology at the Dana-Farber Cancer Institute, highlighted a critical gap in the treatment of patients facing metastatic triple-negative breast cancer. Many do not progress beyond first-line therapy, often due to deteriorating health or mortality, underscoring the urgent need for improved treatment modalities.

The clinical trial engaged 443 participants from 26 different countries, ensuring a diverse demographic. Patients were randomly assigned to either a treatment group receiving sacituzumab govitecan combined with pembrolizumab or a control group treated with the standard chemotherapy and pembrolizumab.

Key Findings

After a median follow-up period of 14 months, the data reveal a notable improvement in progression-free survival for the combination therapy. Patients in the sacituzumab govitecan and pembrolizumab cohort experienced a progression-free survival of 11.2 months, compared to 7.8 months for those receiving chemotherapy.

• Risk Reduction: The risk of disease progression was reduced by 35% in the sacituzumab treatment arm compared to the chemotherapy arm.
• Duration of Response: Patients receiving the combination therapy maintained a median response duration of 16.5 months, significantly longer than the 9.2 months observed in the chemotherapy cohort.

Adverse Events

The analysis also monitored adverse effects related to each treatment method. The most common severe side effects in the sacituzumab group included neutropenia (43%) and diarrhea (10%). Meanwhile, severe adverse events associated with chemotherapy included neutropenia (45%), anemia (16%), and thrombocytopenia (14%). This profile indicates that while both regimens have risks, the combination therapy appears to have a more favorable overall safety profile.

Implications and Future Directions

Dr. Jane Lowe Meisel, Co-Director of Breast Medical Oncology at the Winship Cancer Institute, emphasized that the findings from this study indicate the promising potential of sacituzumab govitecan and pembrolizumab to establish a new standard of care for patients at initial diagnosis of this aggressive cancer.

Researchers are committed to tracking these patients to further explore the overall survival benefits of the combination treatment versus traditional chemotherapy. Furthermore, this combination is being investigated in various other breast cancer patient populations, including those with HER2-negative metastatic breast cancer and early-stage triple-negative breast cancer.

Conclusion

The positive results from the ASCENT-04/KEYNOTE-D19 trial heralds a hopeful advancement in treatment paradigms for triple-negative breast cancer, potentially offering a more effective and tolerable option for an otherwise challenging cancer type.