Olubukola Ayodele, Breast Cancer Lead at University Hospitals of Leicester NHS Trust, shared a post on LinkedIn:
“The era of tumour-agnostic oncology has taken another significant step forward.
The European Commission has approved trastuzumab deruxtecan (T-DXd) as the first HER2-directed tumour-agnostic therapy and antibody-drug conjugate for adults with previously treated HER2-positive (IHC 3+) metastatic solid tumours.
Unlike traditional approvals based on the organ where a cancer starts, this approval is based on a biomarker: HER2 overexpression.
The decision is supported by three Phase II studies:
DESTINY-PanTumor02 (n=111)
Patients with biliary tract, bladder, cervical, endometrial, ovarian and pancreatic cancers.
- ORR 52.3% (95% CI 42.6-61.8)
- Median DOR 21.1 months (95% CI 10.6-25.0)
DESTINY-Lung01 (n=17)
HER2-positive NSCLC.
- ORR 52.9% (95% CI 27.8-77.0)
- Median DOR 6.9 months (95% CI 4.0-9.8)
DESTINY-CRC02 (n=64)
HER2-positive metastatic colorectal cancer.
- ORR 46.9% (95% CI 34.3-59.8)
- Median DOR 5.5 months (95% CI 4.2-8.1)
HER2 overexpression occurs across multiple tumour types and is associated with more aggressive disease and poorer prognosis. This approval offers a new treatment option for patients based on tumour biology rather than where the cancer originated.
An important point is that this approval is specifically for HER2 IHC 3+ disease. It does not extend to HER2-low disease, HER2 gene amplification detected by NGS, or HER2 mutations.
As exciting as this is, it also raises important questions.
- Should HER2 IHC testing now become routine across all metastatic solid tumours?
- Which tissue should we test, the primary tumour or metastatic biopsy?
- Should testing be performed at initial metastatic diagnosis or repeated at progression given tumour heterogeneity and biomarker evolution?
- How do we ensure consistent HER2 IHC scoring across tumour types when pathology standards have largely been developed for breast and gastric cancers?
- Which tumour types derive the greatest clinical benefit?
And perhaps the biggest question: should tumour-agnostic approvals be based on relatively small, single-arm Phase II studies without randomised comparisons to current standards of care?
Precision medicine is undoubtedly the future and expands treatment opportunities for many patients. At the same time, we must balance innovation with evidence, biomarker stewardship, safety and sustainable use of increasingly expensive therapies.
I would love to hear your thoughts.”
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