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-Breast08 is pushing T-DXd beyond monotherapy – into combination strategy.
Phase Ib study (established RP2D across cohorts):
- T-DXd + capecitabine.
- T-DXd + capivasertib (AKT).
- T-DXd + endocrine therapy (anastrozole/fulvestrant).
Signals:
- ORR 40% – 71.4% across cohorts.
- ~60% with capecitabine/capivasertib.
- Strong activity with endocrine combinations in HR+ disease.
- Responses even post CDK4/6 – suggests biologic synergy.
Safety:
- Grade ≥3 AEs common but manageable.
- ILD/pneumonitis remains key risk.
Important nuance:
- Not purely HER2-low.
- Includes HER2-low + HER2-ultralow (IHC 0).
- Testing across HER2 non-amplified disease.
Bigger shift:
We’ve always been taught chemo + endocrine therapy doesn’t work together.
DESTINY-Breast08 challenges that dogma, exciting things to come!”
Title: DESTINY-Breast08: A Phase Ib Study of Trastuzumab Deruxtecan in Combination with Other Anticancer Therapies in Patients with HER2-Low Metastatic Breast Cancer
Authors: Komal Jhaveri, Sherene Loi, Erika Hamilton, Peter Schmid, Carey K. Anders, Laura Testa, Hans Wildiers, Ling-Ming Tseng, Yen-Shen Lu, Yeon Hee Park, Seock-Ah Im, Shin-Cheh Chen, Robyn R. Young, Caron Lloyd, Magdalena Wrona, Cuihong Zhang, Danielle Carroll, Fabrice André
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