Abdu Adem Yesufe, Program Director of Adult Hematology and Medical Oncology Fellowship at St. Paul’s Hospital Millennium Medical College (SPHMMC), shared a post on LinkedIn by Amol Akhade, Senior Consultant at Fortis Hospitals Mumbai, adding:
“It is impressive as a demonstration of the rapid advancement of cancer treatments due to the multitude of clinical trials worldwide. However, for LMICs such as Ethiopia, these options appear distant as we struggle to access even single targeted monoclonal antibodies like trastuzumab…my impression!”
Quoting Amol Akhade’s post:
“T-DXd vs T-DM1 in residual HER2+ early breast cancer (DESTINY-Breast05, NEJM 2025):
A massive win—with important caveats.
The numbers are impressive:
53% reduction in invasive recurrence or death (HR 0.47) Absolute gain of ~9% in 3-year IDFS Better distant recurrence outcomes (HR 0.49)
This is a level of benefit rarely seen in modern adjuvant HER2 therapy.
If the goal is reducing recurrence, T-DXd clearly outperforms T-DM1.
But every victory in oncology comes with its footnotes.
Key limitations that matter:
1.Immature OS data
We cannot declare this a survival-improving strategy with only 47 deaths reported. IDFS ≠ OS, especially in HER2+ disease with excellent salvage options.
2. Short follow-up (~30 months)
HER2+ recurrences often happen late. We may overestimate benefit at early interim analysis. The slope of the curves beyond year 3 will matter more than the early separation.
3.Open-label design
Hard endpoints reduce bias, but subjective toxicities and reporting patterns might shift—especially when one arm carries a known risk like ILD.
4. Interstitial lung disease
ILD occurred in 9.6% with T-DXd vs 1.6% with T-DM1. Even if mostly grade 1–2 here, real-world experience rarely mirrors trial reporting.
The therapeutic index of T-DXd is narrower than the Kaplan–Meier curve suggests.
5. Generalizability
Underrepresentation of Black patients and the need for high-resource ILD monitoring raise questions about global applicability—especially in settings without easy access to serial CT scans or early steroid rescue.
6. No QoL data yet
In a curable population, quality of life is not optional. It is the endpoint. We cannot escalate toxicity without understanding patient-reported outcomes.
7. Heterogeneous residual disease
Not all ‘residual disease’ is equal. The trial does not help us identify which patients derive the necessary level of benefit to justify escalation.
T-DXd is the most effective drug we have ever tested in this setting, and these results will change guidelines immediately.
But enthusiasm must coexist with caution.
We need longer follow-up, OS data, ILD vigilance, and smarter biomarkers before declaring this the new universal standard for every patient with residual HER2+ disease.
Evidence evolves. So should our excitement.”
More posts featuring Abdu Adem Yesufe and Amol Akhade.