Olubukola Ayodele, Breast Cancer Lead at University Hospitals of Leicester NHS Trust, shared a post on LinkedIn:
“The FDA approval of T-DXd in the neoadjuvant and adjuvant HER2-positive early breast cancer setting, based on DESTINY-Breast11 and DESTINY-Breast05, is a major moment.
But for me, the excitement sits alongside important practical questions.
At ESMO 2025, my reflections on these trials were less about ‘Is T-DXd active?‘ We already know it is a very powerful drug.
The bigger question was: Where does it fit best, who benefits most and what are the consequences of moving it earlier?
DB-11 is scientifically exciting. The neoadjuvant data show impressive activity and raise the possibility of deeper responses before surgery. But one issue cannot be ignored: the comparator was not anthracycline-free. Also, the T-Dxd arm was closed early due to lower pCR.
In many real-world settings, we are already trying to reduce anthracycline exposure in selected HER2+ patients because of long-term cardiac toxicity and survivorship concerns.
So DB-11 does not fully answer the pragmatic question many clinicians are facing: How does T-DXd compare with a modern anthracycline-sparing approach?
For me, DB-05 has the more immediate pragmatic pull.
Patients with residual disease after neoadjuvant therapy remain a high-risk group and this is where escalation feels clinically meaningful.
The CNS disease-free benefit is particularly important. In HER2+ breast cancer, the brain remains one of the hardest frontiers. If we can reduce or delay CNS relapse, that is not just statistically relevant. It is deeply patient relevant.
But with early use of T-DXd comes responsibility.
Who benefits most? Probably patients at highest risk of recurrence, residual disease, aggressive biology, nodal burden or those where CNS relapse risk is a major concern.
Who may not need it? That is equally important. Escalation for everyone is not precision medicine.
Cardiac safety matters in HER2 treatment pathways. With T-DXd, we must also remain vigilant about ILD/pneumonitis. Curative intent does not make toxicity less important. It makes it more important.
Then there is resistance.
If T-DXd moves earlier, what do we use later when disease recurs? Are we improving cure, or are we shifting resistance patterns into a more difficult space?
And finally, cost and access.
These are financially demanding treatments. Approvals in high-income countries do not automatically translate into global access. If innovation moves faster than affordability, we risk widening the very inequalities we say we want to close.
So yes, this approval is exciting.
But the real test will be implementation.
Not just can we give T-DXd earlier? But can we give it to the right patients, safely, equitably and without compromising future options?
That is where the real conversation begins.”
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