A Phase III trial (ASCENT-04/KEYNOTE-D19) has shown that the Trodelvy Keytruda combination improves progression-free survival over Keytruda plus chemotherapy in previously untreated PD-L1-positive metastatic triple-negative breast cancer (mTNBC). This pivotal study is the first to demonstrate superiority for a TROP-2 antibody-drug conjugate combined with an immuno-oncology agent in first-line mTNBC treatment.
Improving Treatment Options
The Trodelvy Keytruda combination marks a groundbreaking approach. It is the first time an antibody-drug conjugate (ADC) paired with immunotherapy has shown potential in early metastatic breast cancer treatment. As Dietmar Berger, Chief Medical Officer at Gilead Sciences, highlights, this therapy could redefine options for patients with this challenging cancer.
The ASCENT-04/KEYNOTE-D19 trial was a global, open-label, randomized study involving 443 patients with untreated, PD-L1-positive (CPS ≥ 10) metastatic TNBC. Participants received either:
- 10 mg/kg of Trodelvy on days one and eight of a 21-day cycle plus 200 mg of Keytruda on day one, or
- Chemotherapy (gemcitabine plus carboplatin, paclitaxel, or nab-paclitaxel) combined with Keytruda.
Trodelvy (sacituzumab govitecan-hziy) is an antibody-drug conjugate targeting Trop-2, a protein overexpressed in epithelial cancers. It uses a humanized monoclonal antibody linked to SN-38, the active metabolite of irinotecan, which disrupts topoisomerase I and induces cell death. Unlike conventional chemotherapy, this targeted approach may spare normal cells.
Contextualizing Triple-Negative Breast Cancer
TNBC makes up 10-15% of breast cancer cases. It is hard to treat because it does not respond to hormone or targeted therapies. Current standard treatments give patients only 5-7 months of progression-free survival before disease progression.
In 2020, the FDA approved pembrolizumab (Keytruda) plus chemotherapy for advanced TNBC patients with PD-L1 scores ≥10. This combo improved progression-free survival over chemotherapy alone. Trodelvy is already approved for advanced TNBC patients with at least two prior therapies and for certain metastatic breast cancer cases.
Health Economics and Patient Outcomes
The Trodelvy Keytruda combination improves progression-free survival significantly. This may enhance patients’ quality of life and reduce healthcare use linked to disease progression. If long-term data show better overall survival, its value could grow further.
Gilead will present detailed study results soon and engage with regulators. The safety profile aligns with each drug’s known risks, which may ease approval. However, Trodelvy’s boxed warnings for neutropenia and severe diarrhea could affect reimbursement and treatment protocols.
Future Research Directions
Gilead is studying Trodelvy in more trials, including for PD-L1-negative TNBC patients. This shows confidence in the drug’s broader potential and could reshape TNBC treatment. For more details, see the findings on the Trodelvy Keytruda combination here.
