Matthew Kurian, Assistant Professor of Medicine at the University of Kentucky College of Medicine and Physician at St. Elizabeth Healthcare, shared a post on LinkedIn:
“DESTINY-Breast05. Now in NEJM.
Post-neoadjuvant T-DXd vs T-DM1 in high-risk residual HER2+ early breast cancer:
- Events: 6.2% vs 12.5%
- HR 0.47 (95% CI 0.34–0.66), P<0.001
- 3-yr iDFS: 92.4% vs 83.7%
Distant recurrence:
- 5.1% vs 9.9%
- HR 0.49 (95% CI 0.34–0.71)
High-risk population:
- 81% node-positive
- 52% inoperable at presentation
- 79% dual HER2 therapy pre-op
Safety:
- Grade ≥3 AEs: 50.6% vs 51.9%
- ILD: 9.6% vs 1.6%
- 2 ILD deaths (0.2%)
My take:
This post-neoadjuvant escalation will likely be more common than DB11. Most will still use TCHP neoadjuvantly, reserving DB11 for very high-risk presentations.
T-DM1 still has a role in lower-risk residual disease and not everyone qualifies for DB-05 approach.
Practical points:
- ILD monitoring with CT scans q6 weeks is critical.
- Consider 4 cycles neoadjuvant (DB11) vs 14 cycles adjuvant (DB05) — more exposure, more cumulative toxicity risk.
HER2 curative-intent therapy just evolved.”
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