TABLE 4.

Neoadjuvant Trastuzumab-Deruxtecan Trials

Trial	Inclusion Criteria	Treatment Arms		Primary Objective(s)
ADAPTHER2-IV (NCT05704829) Phase II	HER2-positive Cohort 1: low-intermediate risk for recurrence, cT1c-cT2 (1-3 cm, cN0, cT1a/b excluded) Cohort 2: intermediate-high risk recurrence cT2 (>3 cm-5 cm, cN0) Patients age 65 years and older could be assigned to any cohort	T-DXd × 12 weeks in low-intermediate risk		pCR rate and dDFS rate
		T-DXd × 18 weeks in intermediate-high risk
		THP in low-intermediate risk × 12 weeks		pCR rate and dDFS
		[T or wT] + C + HP × 18 weeks in intermediate-high risk
DESTINY-Breast11 (NCT05113251) Phase III	HER2-positive Clinical stage cT0-4 (including inflammatory BC) and N1-3; or >cT3/N0/M0	T-DXd		pCR rate
		T-DXd followed by wTHP		pCR rate
		ddAC → wTHP		pCR rate
ARIADNE (NCT05900206) Phase II	HER2-positive Clinical stage: cT2 with any cN or cN1-N3 with any cT	T-DXd (cycles 1-3)	Cycle 4-6 on the basis of intrinsic molecular (PAM50) subtype Luminal A and ER+: Ribociclib, letrozole, and HP Luminal and ER– or basal-like: EC if no radiologic response after c1-3; if radiologic CR, then continue T-DXd or TCHP/wTCHP × 3 cycles HER2-enriched: T-DXd or TCHP/wTCHP × 3 more cycles	pCR rate
		TCHP or wTCHP (cycles 1-3)
TRIO-US B12 TALENT (NCT04553770) Phase II	HER2 low (1+ or 2+ by IHC and FISH negative) Clinical stage: cT2 or if cN1/N2 the tumor must be considered operable Hormone receptor–positive as per ASCO/CAP guideline	T-DXd		pCR rate
		T-DXd + anastrazole		pCR rate

Abbreviations: BC, breast cancer; C, carboplatin; CAP, College of American Pathologists; DFS, disease-free survival; ddAC, dose-dense doxorubicin and cyclophosphamide; dDFS, distant DFS; EC, epirubicin and cyclophosphamide; ER, estrogen receptor; H, trastuzumab; HER2, human epidermal growth factor receptor 2; P, pertuzumab; pCR, pathological complete response; T, docetaxel; T-Dxd, trastuzumab deruxtecan; wT, paclitaxel.