Olubukola Ayodele, Breast Cancer Lead at University Hospitals of Leicester NHS Trust, shared a post on LinkedIn:
“One of the hardest realities in metastatic triple negative breast cancer is that some patients never receive a second line of therapy. The disease can progress quickly. Performance status can deteriorate. Opportunities can be lost.
As a breast oncologist with a special interest in metastatic breast cancer, this is why the ASCENT-03 and ASCENT-04 results feel particularly important.
For years, first-line treatment has largely depended on standard chemotherapy and PD-L1 status:
- PD-L1 positive: chemotherapy + pembrolizumab
- PD-L1 negative: chemotherapy alone
What is the difference between ASCENT-03 and ASCENT-04?
ASCENT-03
Can we do better than chemotherapy when immunotherapy is not an option? In patients with PD-L1-negative disease, sacituzumab govitecan improved:
• PFS: 9.7 vs 6.9 months
• HR 0.62 (38% reduction in risk of progression or death)
• ORR: 51% vs 39%
• Duration of response: 12.2 vs 7.2 months
ASCENT-04
Can we improve outcomes in PD-L1-positive disease? Sacituzumab govitecan plus pembrolizumab improved:
• PFS: 11.2 vs 7.8 months
• HR 0.65 (35% reduction in risk of progression or death)
• ORR: 60% vs 53%
• Duration of response: 16.5 vs 9.2 months
The FDA has now approved both indications, while the European Commission has approved the PD-L1-negative indication.
Together, they move an antibody-drug conjugate into the first-line setting regardless of PD-L1 status. This matters because patients were not having the opportunity to receive innovative treatments because of the above mentioned reasons.
I still have important questions such as:
- Would the overall survival data be as compelling?
- How should we sequence ADCs?
- Which patients derive the greatest benefit?
- How do we ensure equitable access?
We are witnessing a shift in how we think about first-line treatment in metastatic TNBC and it represents HOPE for the most challenging subtype of breast cancer.
For me the real impact will be measured in how these clinical trials outcomes translate into everyday practice and if the real world outcomes are similar.”
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