DESTINY-Breast03 Trial

ENHERTU efficacy and safety evaluated in DESTINY-Breast03—
a head-to-head Phase 3 clinical trial powered for PFS (BICR)1,2

A multicenter, open-label, randomized study to compare the efficacy and safety of ENHERTU vs T-DM1 (ado-trastuzumab emtansine)

DESTINY-Breast03 Study Schema. Patients (N=524) with confirmed HER2+ unresectable and/or mBC, who received prior trastuzumab and taxane therapy for metastatic disease or developed disease recurrence during or within 6 months of completing adjuvant therapy, and/or with clinically stable, treated brain metastases were included. Stratification factors included history of visceral disease, hormone receptor status, and prior treatment with pertuzumab. Patients were randomized 1:1 to ENHERTU 5.4 mg/kg Q3W (n=261) and T-DM1 3.6 mg/kg Q3W (n=263). DESTINY-Breast03 Study Schema. Patients (N=524) with confirmed HER2+ unresectable and/or mBC, who received prior trastuzumab and taxane therapy for metastatic disease or developed disease recurrence during or within 6 months of completing adjuvant therapy, and/or with clinically stable, treated brain metastases were included. Stratification factors included history of visceral disease, hormone receptor status, and prior treatment with pertuzumab. Patients were randomized 1:1 to ENHERTU 5.4 mg/kg Q3W (n=261) and T-DM1 3.6 mg/kg Q3W (n=263).
Primary endpoint
  • PFS (BICR)a
Secondary endpoints
  • OS, confirmed ORRb (BICR),a PFS (investigator)
Select exclusion criteria
  • History of ILD/pneumonitis requiring steroids or ILD/pneumonitis at screening
  • Clinically significant cardiac disease
  • Untreated and symptomatic brain metastasesc
  • ECOG performance status >1
  • Prior treatment with an anti-HER2 ADC in the metastatic setting

aBased on RECIST v1.1.1

bAnalysis was performed based on the patients with measurable disease assessed by BICR at baseline (n=248 patients randomized to receive ENHERTU; n=241 for T-DM1).1

cSubjects with treated brain metastases that were no longer symptomatic and who did not require treatment with corticosteroids or anticonvulsants were included in the study if they had recovered from the acute toxic effect of radiotherapy. A minimum of 2 weeks must have elapsed between the end of whole brain radiotherapy and study enrollment.3

DESTINY-Breast03 is the first and only head-to-head study of ENHERTU vs T-DM12

Patient demographics were balanced between treatment arms

Select baseline patient demographics and disease characteristics2,3


ENHERTU (n=261) T-DM1 (n=263)
Age, median 54 years (range: 27-83) 54 years (range: 20-83)
Female 99.6% 99.6%
White 27% 27%
Asian 58% 62%
Black/African American 4% 3%
Other race 10% 8%
ECOG performance status
at baseline
0 59% 67%
1 41% 33%
Hormone receptor status Positive: 50% Positive: 51%
Previous systemic cancer therapyd Trastuzumab + taxane 99.6% 99.6%
Pertuzumab 62.1% 60.1%
Prior lines of therapy in the metastatic
setting (includes rapid progressors as
1 line of treatment)e
0-1 50.6% 47.9%
2+ 49.4% 52%

dAll patients received at least 1 prior cancer therapy. One patient with prior T-DM1 treatment was enrolled in error in the ENHERTU arm.

eRapid progressors defined as progression within 6 months of (neo)adjuvant therapy or 12 months if regimen contained pertuzumab. Line of therapy does not include endocrine therapy.

Sites of metastases3


ENHERTU (n=261) T-DM1 (n=263)
Presence of visceral disease 71% 70%
Lung metastases 43% 49%
Liver metastases 35% 29%
Brain metastasesf 24% 20%

fIncluded all patients with a reported history of CNS metastases at baseline. Subjects with treated brain metastases that were no longer symptomatic and who did not require treatment with corticosteroids or anticonvulsants were included in the study if they had recovered from the acute toxic effect of radiotherapy. A minimum of 2 weeks must have elapsed between the end of whole brain radiotherapy and study enrollment.3

Downloadable Resource for You:

    Take a closer look at the DESTINY-Breast03
    efficacy and safety data

ADC, antibody-drug conjugate; BICR, blind independent central review; CNS, central nervous system; ECOG, Eastern Cooperative Oncology Group; HER2, human epidermal growth factor receptor 2; ILD, interstitial lung disease; mBC, metastatic breast cancer; ORR, objective response rate; OS, overall survival; PFS, progression-free survival; Q3W, every 3 weeks; RECIST, Response Evaluation Criteria in Solid Tumors; T-DM1, ado-trastuzumab emtansine.