ENHERTU was investigated in DESTINY-Breast06
A Phase 3, international, randomized, open-label trial designed to evaluate ENHERTU vs chemotherapy in eligible patients with HR+/HER2-low and HER2-ultralow mBC1-4
Primary endpoint1
- PFS (assessed by BICR) in the HER2-low population
Key secondary endpoints1
- PFS (assessed by BICR) in the overall study population (HER2-low and HER2-ultralow)
- OS in the HER2-low and overall study population (HER2-low and HER2-ultralow)
Select secondary endpoints3
- Confirmed ORR and DOR in the HER2-low population
- Confirmed ORR and DOR in the overall study population (HER2-low and HER2-ultralow)
Select exploratory endpoints2,3
- PFS, ORR, and DOR in the HER2-ultralow population
Stratification factors1
- HER2 IHC status (IHC 1+ or IHC 2+/ISH– or IHC 0 with membrane staining)
- Prior CDK4/6 inhibitor
- Prior taxane in the non-metastatic setting
aDisease progression on at least 2 previous lines of ET with or without a targeted therapy (eg, CDK4/6, mTOR, or PI3K inhibitors) administered for the treatment of metastatic disease.
bOnly 1 line of ET in the metastatic setting required.
cIHC 1+ tumors and IHC 0 tumors were ISH– or ISH untested.
dPatients could have received chemotherapy in the neoadjuvant or adjuvant setting as long as they have had a disease-free interval of >12 months.
eTreatment continued until disease progression or unacceptable toxicity.
fIn the control arm, 60% of patients received capecitabine, 24% nab-paclitaxel, and 16% paclitaxel.
Select baseline patient demographics and clinical characteristics2,4
ENHERTU
5.4 mg/kg (n=436)
Chemotherapy
(n=430)
Age, median
58 (range: 28-87)
57 (range: 32-83)
HER2 IHC scoreg
IHC 1+
55%
54%
ISH 2+/ISH–
27%
27%
IHC 0 with membrane staining
17%
18%
Prior CDK4/6 inhibitor in the metastatic setting
89%
90%
Number of prior lines of ET in the metastatic setting
1
15%
19%
2
68%
67%
≥3
17%
14%
Time to progression on prior ET + CDK4/6 inhibitor
≤6 months
9%
9%
>6 months
91%
91%
Prior chemotherapy in non-metastatic setting
52%
54%
Liver metastases
68%
66%
Visceral disease
86%
85%
ENHERTU
5.4 mg/kg
(n=436)
Chemo-
therapy
(n=430)
Age,
median
58 (range:
28-87)
57 (range:
32-83)
HER2 IHC scoreg
IHC 1+
55%
54%
ISH 2+/ISH–
27%
27%
IHC 0 with membrane staining
17%
18%
Prior CDK4/6 inhibitor in the metastatic setting
89%
90%
Number of prior lines of ET in the metastatic setting
1
15%
19%
2
68%
67%
≥3
17%
14%
Time to progression on prior ET + CDK4/6 inhibitor
≤6 months
9%
9%
>6 months
91%
91%
Prior chemotherapy in non-metastatic setting
52%
54%
Liver metastases
68%
66%
Visceral disease
86%
85%
| ENHERTU 5.4 mg/kg (n=436) |
Chemotherapy (n=430) |
||
|---|---|---|---|
| Age, median | 58 (range: 28-87) | 57 (range: 32-83) | |
| HER2 IHC scoreg | IHC 1+ | 55% | 54% |
| ISH 2+/ISH– | 27% | 27% | |
| IHC 0 with membrane staining | 17% | 18% | |
| Prior CDK4/6 inhibitor in the metastatic setting | 89% | 90% | |
| Number of prior lines of ET in the metastatic setting | 1 | 15% | 19% |
| 2 | 68% | 67% | |
| ≥3 | 17% | 14% | |
| Time to progression on prior ET + CDK4/6 inhibitor | ≤6 months | 9% | 9% |
| >6 months | 91% | 91% | |
| Prior chemotherapy in non-metastatic setting | 52% | 54% | |
| Liver metastases | 68% | 66% | |
| Visceral disease | 86% | 85% | |
| ENHERTU 5.4 mg/kg (n=436) |
Chemo- therapy (n=430) |
|
|---|---|---|
| Age, median |
58 (range: 28-87) |
57 (range: 32-83) |
| HER2 IHC scoreg | ||
| IHC 1+ | 55% | 54% |
| ISH 2+/ISH– | 27% | 27% |
| IHC 0 with membrane staining | 17% | 18% |
| Prior CDK4/6 inhibitor in the metastatic setting | 89% | 90% |
| Number of prior lines of ET in the metastatic setting | ||
| 1 | 15% | 19% |
| 2 | 68% | 67% |
| ≥3 | 17% | 14% |
| Time to progression on prior ET + CDK4/6 inhibitor | ||
| ≤6 months | 9% | 9% |
| >6 months | 91% | 91% |
| Prior chemotherapy in non-metastatic setting | 52% | 54% |
| Liver metastases | 68% | 66% |
| Visceral disease | 86% | 85% |
- Gender: 99.9% were female, 0.1% were male1
- Race/ethnicity: 53% were White, 35% were Asian, 7% were Hispanic/Latino, 0.8% were Black or African American, and 0.1% were American Indian or Alaska Native1
- ECOG PS: 59% had ECOG PS 0 and 39% had ECOG PS 1 at baseline1,h
- 32% of patients had lung metastases1
In DESTINY-Breast06, ~85% of patients had received 1-2 lines of ET in the metastatic setting1
gIHC 1+ tumors and IHC 2+ tumors were ISH–.
h14 patients in the overall study population (5 patients in the ENHERTU group and 9 patients in the chemotherapy group) had missing ECOG PS scores at baseline but had a score of 0 or 1 recorded within 6 days after randomization.
1L, first line; BICR, blinded independent central review; CDK4/6, cyclin-dependent kinases 4 and 6; DOR, duration of response; ECOG, Eastern Cooperative Oncology Group; ET, endocrine therapy; HER2, human epidermal growth factor receptor 2; HR+, hormone receptor-positive; IHC, immunohistochemistry; ISH, in situ hybridization; IV, intravenous; mBC, metastatic breast cancer; mTOR, mammalian target of rapamycin; ORR, objective response rate; OS, overall survival; PI3K, phosphatidylinositol 3-kinase; PFS, progression-free survival; PS, performance score; Q3W, every 3 weeks.