Amol Akhade, Senior Consultant at Fortis Hospitals Mumbai, shared a post on LinkedIn:
“Datopotamab-Deruxtecan Delivers OS Benefit in 1L mTNBC – The ADC Era Enters Its Sequencing Phase
Daiichi Sankyo and AstraZeneca have announced a landmark result:
Datopotamab-Deruxtecan (Dato-DXd, ‘Datroway’) from TROPION-Breast02 has met both co-primary endpoints – overall survival (OS) and progression-free survival (PFS) – versus chemotherapy in first-line, immunotherapy-ineligible metastatic triple-negative breast cancer (mTNBC).
This marks the first-ever ADC to show a clinically meaningful OS benefit over chemotherapy in this setting.
For patients with PD-L1–negative TNBC – roughly two-thirds of this disease – this could be a genuine turning point. Until now, chemotherapy was the only option once immunotherapy was ruled out.
The inevitable comparison
At the same time, Sacituzumab-Govitecan (Trodelvy) from ASCENT-03 has also shown significant PFS benefit but only ‘no OS detriment’ so far.
Two ADCs, both targeting TROP2 and both carrying TOPO-I payloads – yet one crosses the OS bar while the other doesn’t (at least not yet).
This difference – between Dato-DXd (DXd payload) and SG (SN-38 payload) – may appear subtle pharmacologically, but clinically it could shift first-line standards.
The new challenge: sequencing
With multiple ADCs now crowding the metastatic TNBC space – Datroway, Trodelvy, the China-approved Sac-TMT, and even the HER2-low active T-DXd – the problem is no longer discovery.
It’s deployment.
All share similar mechanisms. All deliver TOPO-I poisons.
No trial yet defines the optimal sequence or cross-resistance pattern.
Can one ADC follow another? Does payload class limit response to the next?
We’re entering the ‘sequencing era’ of ADC oncology, where success will depend less on the drug’s design and more on the clinician’s judgment.
The Top Gun analogy
In Top Gun: Maverick, Tom Cruise says –
‘It’s not the plane, it’s the pilot.’
That line feels especially apt today.
These ADCs are advanced aircraft – engineered with precision, packed with power – but what will truly determine patient outcomes is the pilot’s skill: choosing the right ADC for the right patient, in the right sequence.
‘It’s not the plane, it’s the pilot.’
And in this new ADC battlefield – it’s not just the payload… It’s the oncologist.”
More posts featuring Amol Akhade.
