First UK real-world study shows promise for sacituzumab govitecan in metastatic breast cancer

By Dr. Priyom Bose, Ph.D. Apr 26 2024 Reviewed by Lily Ramsey, LLM

A recent British Journal of Cancer evaluated the real-world safety and efficacy of sacituzumab govitecan (SG) against metastatic triple-negative breast cancer (mTNBC).

Study:  Real world study of sacituzumab govitecan in metastatic triple-negative breast cancer in the United Kingdom . Image Credit: Gorodenkoff/Shutterstock.com Background

Every year, more than 8,000 people in the UK are diagnosed with TNBC, which accounts for 15% of all breast cancer cases. In comparison to all sub-types of breast cancer, TNBC has the poorest prognosis.

This disease is extremely heterogeneous and has limited targeted treatment options. Conventionally, patients diagnosed with TNBC were treated with chemotherapy. 

Recently, SG received approval for treatment with TNBC. SG is an antibody-drug conjugate (ADC) that is composed of the humanized anti-trophoblast antigen 2 (anti-TROP2) antibody conjugated to an active metabolite of irinotecan called SN-38.

Multiple cancer types, including TNBC, have been associated with the overexpression of TROP2, a transmembrane protein. The binding of SG with TROP2 mediates the internalization of SN-38, which subsequently induces anti-tumour effects upon hydrolysis of the linker.

ASCENT, a phase 3 randomized trial (NCT02574455), was conducted to evaluate the efficacy of SG and compare the findings with the effectiveness of chemotherapy of the physician’s choice for treating TNBC.

In comparison to chemotherapy, SG demonstrated better survival outcomes. Considering the findings of this trial, the U.S. Food and Drug Administration (FDA) approved SG for patients with mTNBC, particularly those who received at least two lines of prior systemic therapy. About the study

Extending the research cited above, the current study investigated the safety and efficacy of SG for mTNBC in real-world settings. The relevant data on mTNBC patients were obtained from sixteen tertiary UK cancer centers. Related StoriesDASH diet may lower the risk of cardiovascular disease in breast cancer survivorsMONET: New AI tool enhances medical imaging with deep learning and text analysisNew research pinpoints key pathways in prostate cancer's vulnerability to ferroptosis

The selected patients received at least one dose of SG in addition to at least two prior lines of chemotherapy. The efficacy of this drug was assessed in terms of median progression-free survival (mPFS), median overall survival (mOS), and safety.

A total of 132 patients were included in this study, among which 131 were females and one male.

The median age of the patients was 56 years. The majority of patients in this cohort had visceral metastases, followed by central nervous system and liver metastases. 

SG treatment was administered as a second-line treatment for 28% of the cohort and a third line for 31% of the cohort. Around 41% of patients who were treated with SG underwent three or more prior lines of chemotherapy. Study findings

A shorter mOS of 8.7 months was noted compared to the ASCENT trial. The observed mPFS was similar, and the lack of enough later events prevented the computation of the upper confidence interval of mOS. A potential reason for the shorter mOS is the inclusion of patients with poorer performance status (PS).

The median number of prior anti-cancer regimens in the ASCENT trial was 3. This included lines in the neo-adjuvant/adjuvant settings.

Twenty-nine percent of patients had received four or more previous lines of treatment, while 71% had received 2 or 3 prior lines. This was similar to the current study, where the median number of prior anti-cancer regimens was 2 in the metastatic setting.

No significant differences were noted when survival was compared based on the number of previous lines of treatment in the metastatic setting.

In the metastatic setting, patients who received 1 or 2 prior lines of treatment did not reach the mOS. This could be due to a shorter follow-up time of this cohort and the fact that such patients might be earlier in their treatment path and live longer.

Patients with central nervous system disease were also included in this analysis. Individuals with brain metastasis who had not received any prior radiotherapy (RT) showed a very poor mOS of 2.5 months.

The precise reason for withholding RT is unclear, but it could be that these patients were possibly not considered fit enough to undergo RT.

Data were not collected on using granulocyte colony-stimulating factor (G-CSF). Currently, in the UK, prescribing G-CSF is at the discretion of the concerned clinician. More research should be conducted on the use and timing of G-CSF.

Further investigation is also needed on the impact of G-CSF on neutropenia, dose reductions, and treatment breaks. Conclusions

In sum, the current study investigated the safety and efficacy of SG for mTNBC in real-world settings. The findings confirm substantial anti-tumor activity in the UK cohort.

The safety profile was also in line with clinical trial experience. Superior survival rates were noted in patients with better performance status. The efficacy was also maintained in patients with central nervous system disease. Journal reference:

Hanna, D. et al. (2024) Real world study of sacituzumab govitecan in metastatic triple-negative breast cancer in the United Kingdom. British Journal of Cancer. pp.1-5. doi: https://doi.org/10.1038/s41416-024-02685-9. https://www.nature.com/articles/s41416-024-02685-9