Breast Cancer, Breast Neoplasms, HER2-positive Early Breast Cancer
Conditions
Keywords
Trastuzumab Trastuzumab Deruxtecan (T-DXd; DS-8201a), DESTINY-BREAST11, Receptor, ErbB-2, breast neoplasms, Antineoplastic Agents, Phytogenic, Antineoplastic Agents;Molecular Mechanisms of Pharmacological Action, DB11, Enhertu, HER2 (human epidermal growth factor receptor 2), breast cancer
Brief summary
This study will look at the efficacy and safety of trastuzumab deruxtecan (T-DXd) in a neoadjuvant setting, in high-risk, HER2-positive early non-metastatic breast cancer.
Detailed description
The target population of interest in this study is participants with high-risk HER2-positive early-stage breast cancer. The purpose of this study is to determine the efficacy and safety of T-DXd neoadjuvant therapy. Participants will be randomised to one of 3 arms: T-DXd monotherapy (Arm A), T-DXd followed by THP (Arm B), or ddAC-THP (Arm C).
Interventions
DRUGTrastuzumab Deruxtecan
administered by intravenous infusion
DRUGPaclitaxel
administered by intravenous infusion
DRUGTrastuzumab
administered by intravenous infusion
DRUGPertuzumab
administered by intravenous infusion
DRUGDoxorubicin
administered by intravenous infusion
DRUGcyclophosphamide
administered by intravenous infusion
Sponsors
AstraZeneca
Daiichi Sankyo
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
Participants are assigned to one of three arms in parallel for the duration of the study.
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Key Inclusion Criteria: * Patients must be at least 18 years of age. * Histologically documented HER2-positive early breast cancer (EBC) participants, including clinical stage at presentation (based on mammogram or breast MRI assessment): T0-4 (inclusive of inflammatory breast cancer), N1-3, M0 or ≥ T3, N0, M0 as determined by the AJCC staging system, 8th edition * ECOG performance status of 0 or 1 at randomization * Adequate organ and bone marrow function * LVEF ≥ 50% within 28 days before randomization * FFPE tissue block (2 cores) or 20 freshly-cut, serial tumor slides for HER2 assessment by central lab. If blocks are incomplete or fewer than 20 slides are available, participants may be eligible following discussion with the AstraZeneca Study Physician
Exclusion criteria
* prior history of invasive breast cancer * stage IV breast cancer (determined by AJCC staging system) * any primary malignancy within 3 years (except resected non-melanoma skin cancer, curatively treated in situ disease) Note: This includes a second current breast primary malignancy (ie, bilateral breast cancer) * history of DCIS (except those treated with mastectomy \>5 years prior to current diagnosis) * History of, or current, ILD/pneumonitis * Prior systemic therapy for the treatment of breast cancer * Previous treatment with anthracyclines, cyclophosphamide or taxanes for any malignancy
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Rate of Pathologic Complete Response (pCR). | Through to definitive surgery or discontinuation/withdrawal from study, up to a maximum of approximately 40 months from randomization to primary pCR DCO (12MAR2025) | Proportion of participants who have no evidence by Hematoxylin \& Eosin (H\&E) staining of residual invasive disease in the complete resected breast specimen and all sampled regional lymph nodes (ypT0/Tis ypN0) by central evaluation following completion of neoadjuvant therapy. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Event-Free Survival (Count) | Up to a maximum of approximately 65 months from randomization to EFS final analysis DCO (Apr 2027) | Event-free survival (EFS) is defined as the time from date of randomization until disease progression precluding initial surgery, invasive disease recurrence (local, regional, distant, or contralateral), or death from any cause. |
| Event-Free Survival (Duration) | Up to a maximum of approximately 65 months from randomization to EFS final analysis DCO (Apr 2027) | Event-free survival (EFS) is defined as the time from date of randomization until disease progression precluding initial surgery, invasive disease recurrence (local, regional, distant, or contralateral), or death from any cause. |
Countries
Brazil, Bulgaria, Canada, China, Germany, India, Italy, Japan, Peru, Philippines, Poland, Russia, Saudi Arabia, South Korea, Spain, Taiwan, Thailand, United States
Participant flow
Recruitment details
The study is active, not recruiting and conducted in 18 countries worldwide across 147 centres, with 927 patients who were randomized up until 24th April 2024. Results are reported for the study at the data cut-off for the primary analysis for pathologic complete response (pCR) on 12th March 2025.
Pre-assignment details
Eligible patients had histologically documented human epidermal growth factor receptor 2 (HER2) - positive early stage breast cancer. Eligible patients were randomized in a 1:1:1 ratio using an interactive response technology (IRT) to receive either Arm A: Trastuzumab deruxtecan (T-DXd), Arm B: Trastuzumab deruxtecan followed by Paclitaxel + trastuzumab + pertuzumab (T-DXd-THP) or Arm C: Doxorubicin + cyclophosphamide followed by Paclitaxel + trastuzumab + pertuzumab (ddAC-THP).
Baseline characteristics
| Characteristic | — |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 105 Participants |
| Age, Categorical Between 18 and 65 years | 822 Participants |
| Age, Continuous | 50.1 Years STANDARD_DEVIATION 11.21 |
| BMI | 25.724 kg/m2 STANDARD_DEVIATION 5.213 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 29 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 292 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Height | 160.248 cm STANDARD_DEVIATION 7.0934 |
| Hormone receptor status by local assessment and central assessment of HER2- positive status Hormone receptor status: ER and/or PgR positive HER2-positive status: IHC 3+ | 605 Participants |
| Hormone receptor status by local assessment and central assessment of HER2- positive status Hormone receptor status: ER and/or PgR positive HER2-positive status: Other | 23 Participants |
| Hormone receptor status by local assessment and central assessment of HER2- positive status Hormone receptor status: ER and PgR negative HER2-positive status: IHC 3+ | 79 Participants |
| Hormone receptor status by local assessment and central assessment of HER2- positive status Hormone receptor status: ER and PgR negative HER2-positive status: Other | 6 Participants |
| Hormone receptor status by local assessment and central assessment of HER2- positive status Hormone receptor status: Total HER2-positive status: IHC 3+ | 289 Participants |
| Hormone receptor status by local assessment and central assessment of HER2- positive status Hormone receptor status: Total HER2-positive status: Other | 32 Participants |
| Race/Ethnicity, Customized American Indian or Alaska Native | 4 Participants |
| Race/Ethnicity, Customized Asian | 160 Participants |
| Race/Ethnicity, Customized Black or African American | 7 Participants |
| Race/Ethnicity, Customized Native Hawaiian or other Pacific Islander | 2 Participants |
| Race/Ethnicity, Customized Not reported | 4 Participants |
| Race/Ethnicity, Customized Other | 9 Participants |
| Race/Ethnicity, Customized White | 139 Participants |
| Region of Enrollment Brazil | 14 Participants |
| Region of Enrollment Bulgaria | 0 Participants |
| Region of Enrollment Canada | 19 Participants |
| Region of Enrollment China | 43 Participants |
| Region of Enrollment Germany | 16 Participants |
| Region of Enrollment India | 20 Participants |
| Region of Enrollment Italy | 31 Participants |
| Region of Enrollment Japan | 25 Participants |
| Region of Enrollment Korea | 51 Participants |
| Region of Enrollment Peru | 15 Participants |
| Region of Enrollment Philippines | 47 Participants |
| Region of Enrollment Poland | 68 Participants |
| Region of Enrollment Russia | 5 Participants |
| Region of Enrollment Saudi Arabia | 17 Participants |
| Region of Enrollment Spain | 64 Participants |
| Region of Enrollment Taiwan | 8 Participants |
| Region of Enrollment Thailand | 10 Participants |
| Region of Enrollment United States of America | 32 Participants |
| Sex: Female, Male Female | 320 Participants |
| Sex: Female, Male Male | 0 Participants |
| Weight | 64.879 kg STANDARD_DEVIATION 12.3807 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 8 / 286 | 3 / 321 | 9 / 320 |
| other Total, other adverse events | 269 / 283 | 306 / 320 | 307 / 312 |
| serious Total, serious adverse events | 29 / 283 | 34 / 320 | 63 / 312 |
Outcome results
None listed