Breast Cancer
Conditions
Keywords
Anti-HER2-Antibody Drug Conjugate (ADC), Unresectable or Metastatic, Human epidermal growth factor receptor 2 (HER2)-low, DESTINY - Breast 04
Brief summary
This study will compare DS-8201a to physician choice standard treatment. Participants must have HER2-low breast cancer that has been treated before. Participants' cancer: * Cannot be removed by an operation * Has spread to other parts of the body
Detailed description
This is a randomized, 2-arm, Phase 3, open-label, multicenter study to compare the safety and efficacy of trastuzumab deruxtecan versus the physician's choice (2:1) in HER2-low, unresectable and/or metastatic breast cancer participants. The Sponsor proposes to define a new HER2-low population in this trial including tumors with IHC 1+ and IHC 2+/ISH- HER2 expression.
Interventions
DS-8201a is a lyophilized powder reconstituted into a sterile aqueous solution (100 mg/5 mL) to be administered intravenously
DRUGCapecitabine
Administered according to label, as one option for Physician's Choice (determined before randomization)
DRUGEribulin
Administered according to label, as one option for Physician's Choice (determined before randomization)
DRUGGemcitabine
Administered according to label, as one option for Physician's Choice (determined before randomization)
DRUGPaclitaxel
Administered according to label, as one option for Physician's Choice (determined before randomization)
DRUGNab-paclitaxel
Administered according to label, as one option for Physician's Choice (determined before randomization)
Sponsors
Daiichi Sankyo Co., Ltd.
AstraZeneca
Daiichi Sankyo
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
Parallel model, randomized at a 2:1 ratio
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Is the age of majority in their country * Has pathologically documented breast cancer that: 1. Is unresectable or metastatic 2. Has low-HER2 expression defined as IHC 2+/ISH- or IHC 1+ (ISH- or untested) 3. Is HR-positive or HR-negative 4. Has progressed on, and would no longer benefit from, endocrine therapy 5. Has been treated with 1 to 2 prior lines of chemotherapy/adjuvant in the recurrent or metastatic setting 6. Was never previously HER2-positive (ICH 3+ or ISH+) on prior pathology testing (per American Society of Clinical Oncology-College of American Pathologists \[ASCO-CAP\] guidelines) * Has documented radiologic progression (during or after most recent treatment) * Has adequate archival tumor samples available or is wiling to provide fresh biopsies prior to randomization for: 1. assessment of HER2 status 2. assessment of post-treatment status * Has at least 1 measurable lesion per Response Evaluation Criteria In Solid Tumors 1.1 * Has protocol-defined adequate cardiac, bone marrow, renal, hepatic and blood clotting functions * Male and female participants of reproductive/childbearing potential, agrees to follow instructions for method(s) of contraception and agrees to avoid preserving ova or sperm for at least 4.5 months after treatment (or longer, per locally approved labels)
Exclusion criteria
* Is ineligible for all options in the physician's choice arm * Has breast cancer ever assessed with high-HER2 expression * Has previously been treated with any anti-HER2 therapy, including an antibody drug conjugate * Has uncontrolled or significant cardiovascular disease * Has spinal cord compression or clinically active central nervous system metastases * Has history of (noninfectious) interstitial lung disease (ILD)/pneumonitis that required steroids, has current ILD/pneumonitis, or suspected ILD/pneumonitis that cannot be ruled out by imaging at screening * Has any medical history or condition that per protocol or in the opinion of the investigator is inappropriate for the study
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Progression-free Survival (PFS) Based on Blinded Independent Central Review (BICR) in the Hormone Receptor-Positive Cohort in Participants With HER2-low Breast Cancer | From the date of randomization to the earliest date of the first objective documentation of radiographic disease progression or death due to any cause, up to approximately 3 years | Progression-free survival (PFS), defined as at least a 20% increase in the sum of diameters of target lesions, was assessed from the date of randomization to the date of the first radiographic disease progression or death due to any cause, whichever came first. PFS was based on blinded independent central review (BICR) in the hormone receptor-positive cohort according to modified Response Evaluation Criteria in Solid Tumors (mRECIST) version 1.1. Median PFS was from Kaplan-Meier analysis. Confidence interval for median was computed using the Brookmeyer-Crowley method. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Progression-free Survival (PFS) Based on Blinded Independent Central Review (BICR) in Participants With HER2-low Breast Cancer (All Patients) Regardless of Hormone Receptor Status | From the date of randomization to the earliest date of the first objective documentation of radiographic disease progression or death due to any cause, up to approximately 3 years | Progression-free survival (PFS), defined as at least a 20% increase in the sum of diameters of target lesions, was assessed from the date of randomization to the date of the first radiographic disease progression or death due to any cause, whichever came first. PFS was based on blinded independent central review (BICR) according to modified Response Evaluation Criteria in Solid Tumors (mRECIST) version 1.1. Median PFS was from Kaplan-Meier analysis. Confidence interval for median was computed using the Brookmeyer-Crowley method. |
| Progression-free Survival Based on Investigator Assessment in the Hormone Receptor-Positive Cohort in Participants With HER2-low Breast Cancer | From the date of randomization to the earliest date of the first objective documentation of radiographic disease progression or death due to any cause, up to approximately 3 years | Progression-free survival (PFS), defined as at least a 20% increase in the sum of diameters of target lesions, was assessed from the date of randomization to the date of the first radiographic disease progression or death due to any cause, whichever came first. PFS was based on investigator assessment in the hormone receptor-positive cohort according to modified Response Evaluation Criteria in Solid Tumors (mRECIST) version 1.1. Median PFS was from Kaplan-Meier analysis. Confidence interval for median was computed using the Brookmeyer-Crowley method. |
| Progression-free Survival Based on Investigator Assessment in Participants With HER2-low Breast Cancer (All Patients) | From the date of randomization to the earliest date of the first objective documentation of radiographic disease progression or death due to any cause, up to approximately 3 years | Progression-free survival (PFS), defined as at least a 20% increase in the sum of diameters of target lesions, was assessed from the date of randomization to the date of the first radiographic disease progression or death due to any cause, whichever came first. PFS was based on investigator assessment according to modified Response Evaluation Criteria in Solid Tumors (mRECIST) version 1.1. Median PFS was from Kaplan-Meier analysis. Confidence interval for median was computed using the Brookmeyer-Crowley method. |
| Overall Survival (OS) in the Hormone Receptor-Positive Cohort in Participants With HER2-low Breast Cancer | From the date of randomization up to the date of death due to any cause, up to approximately 3 years | Overall survival (OS) was defined as the time from the date of randomization to the date of death due to any cause. If there was no death reported for a participant before the data cutoff for OS analysis, OS was censored at the last contact date at which the participant was known to be alive. |
| Number of Overall Survival Events (Deaths) | From the date of randomization up to the date of death due to any cause, up to approximately 3 years | — |
| Best Overall Response and Confirmed Objective Response Rate (ORR) in the Hormone Receptor-Positive Cohort in Participants With HER2-low Breast Cancer | From screening and every 6 weeks up to withdrawal of subject consent, progressive disease (PD), or unacceptable toxicity, up to approximately 3 years | Best overall response rate and confirmed objective response rate (ORR) were assessed by blinded independent central review (BICR) and investigator assessment. Complete response (CR) was defined as a disappearance of all target lesions, partial response (PR) was defined as at least a 30% decrease in the sum of diameters of target lesions, and stable disease (SD) was defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease (PD; at least a 20% increase in the sum of diameters of target lesions. Confirmed ORR was defined as the number of participants with complete and partial responses and confirmed by a second assessment. |
| Best Overall Response and Confirmed Objective Response Rate (ORR) in Participants With HER2-low Breast Cancer (All Patients) | From screening and every 6 weeks up to withdrawal of subject consent, progressive disease (PD), or unacceptable toxicity, up to approximately 3 years | Best overall response rate and confirmed objective response rate (ORR) were assessed by blinded independent central review (BICR) and investigator assessment. Complete response (CR) was defined as a disappearance of all target lesions, partial response (PR) was defined as at least a 30% decrease in the sum of diameters of target lesions, and stable disease (SD) was defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease (PD; at least a 20% increase in the sum of diameters of target lesions. Confirmed ORR was defined as the number of participants with complete and partial responses and confirmed by a second assessment. |
| Duration of Response in the Hormone Receptor-Positive Cohort in Participants With HER2-low Breast Cancer | From the date of the first documented objective response (CR or PR) to the first documented disease progression or death, whichever occurs first, up to approximately 3 years | Duration of Response (DoR) is defined as the date of the first documented objective response (complete response \[CR\] or partial response \[PR\]) to the first documented disease progression or death, whichever occurs first. DoR was based on blinded independent central review (BICR) and investigator assessment. Median was from Kaplan-Meier estimate. Confidence interval for median was computed using the Brookmeyer-Crowley method. |
| Duration of Response in Participants With HER2-low Breast Cancer (All Patients) | From the date of the first documented objective response (CR or PR) to the first documented disease progression or death, whichever occurs first, up to approximately 3 years | Duration of Response (DoR) is defined as the date of the first documented objective response (complete response \[CR\] or partial response \[PR\]) to the first documented disease progression or death, whichever occurs first. DoR was based on blinded independent central review (BICR) and investigator assessment. Median was from Kaplan-Meier estimate. Confidence interval for median was computed using the Brookmeyer-Crowley method. |
| Overall Survival (OS) in All Patients | From the date of randomization up to the date of death due to any cause, up to approximately 3 years | Overall survival (OS) was defined as the time from the date of randomization to the date of death due to any cause. If there was no death reported for a participant before the data cutoff for OS analysis, OS was censored at the last contact date at which the participant was known to be alive. |
Other
| Measure | Time frame | Description |
|---|---|---|
| All-Cause Mortality | From the date of randomization up to the date of death due to any cause, up to approximately 3 years | All-cause mortality is defined as all anticipated and unanticipated deaths due to any cause, with the number and frequency of such events by arm or comparison group of the clinical study. |
Countries
Austria, Belgium, Canada, China, France, Germany, Greece, Hungary, Israel, Italy, Japan, Portugal, Russia, South Korea, Spain, Sweden, Switzerland, Taiwan, United Kingdom, United States
Participant flow
Recruitment details
A total of 557 participants were enrolled and randomized to treatment at 161 study sites in the United States (27 study sites), Japan (18 sites), France (16 sites), China (15 sites), Italy (13 sites), Spain (12 sites), Greece (8 sites), Portugal (8 sites), Republic of Korea (8 sites), Israel (6 sites), Switzerland (6 sites), Austria (4 sites), Belgium (4 sites), Russia (3 sites), Sweden (3 sites), Taiwan (3 sites), Unted Kingdom (3 sites), Canada (2 sites), and Hungary (2 sites).
Pre-assignment details
All participants had been previously treated with at least 1 and no more than 2 prior lines of chemotherapy in the recurrent or metastatic setting. The treatment chosen for the Physician's Choice arm was based on the label approved in the country of drug administration. The Physician's Choice group was combined to ensure an appropriate sample size for the comparator group.
Participants by arm
| Arm | Count |
|---|---|
| Trastuzumab Deruxtecan (T-DXd) Participants with HER2-low, unresectable, and/or metastatic breast cancer who were previously treated with chemotherapy were randomized to receive an intravenous infusion of DS8201a (initial dose of 5.4 mg/kg) over approximately 90 minutes. If there was no infusion-related reaction (IRR), T-DXd doses after the initial dose of 5.4 mg/kg were infused over a minimum of 30 minutes. | 373 |
| Physician's Choice Participants with HER2-low, unresectable, and/or metastatic breast cancer who were previously treated with chemotherapy and randomized to a physician's choice (capecitabine, eribulin, gemcitabine, paclitaxel, and nab-paclitaxel) in which the dose, regimen, administration, and dose modification followed the label approved in the country of drug administration or the National Comprehensive Cancer Network guidelines. | 184 |
| Total | 557 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 60 | 14 |
| Overall Study | Clinical progression by investigator | 10 | 8 |
| Overall Study | Death | 5 | 2 |
| Overall Study | Lost to Follow-up | 0 | 1 |
| Overall Study | Other | 2 | 0 |
| Overall Study | Physician Decision | 4 | 3 |
| Overall Study | Progressive disease as per RECIST v1.1 | 220 | 130 |
| Overall Study | Randomized, but not treated | 2 | 12 |
| Overall Study | Withdrawal by Subject | 12 | 11 |
Baseline characteristics
| Characteristic | Trastuzumab Deruxtecan (T-DXd) | Physician's Choice | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 83 Participants | 48 Participants | 131 Participants |
| Age, Categorical Between 18 and 65 years | 290 Participants | 136 Participants | 426 Participants |
| Age, Continuous | 56.5 years STANDARD_DEVIATION 10.6 | 56.5 years STANDARD_DEVIATION 11.5 | 56.5 years STANDARD_DEVIATION 10.9 |
| Race/Ethnicity, Customized Asian | 151 Participants | 72 Participants | 223 Participants |
| Race/Ethnicity, Customized Black or African American | 7 Participants | 3 Participants | 10 Participants |
| Race/Ethnicity, Customized Missing | 0 Participants | 1 Participants | 1 Participants |
| Race/Ethnicity, Customized Native Hawaiian or other Pacific Islander | 1 Participants | 0 Participants | 1 Participants |
| Race/Ethnicity, Customized Other | 38 Participants | 17 Participants | 55 Participants |
| Race/Ethnicity, Customized White | 176 Participants | 91 Participants | 267 Participants |
| Sex: Female, Male Female | 371 Participants | 184 Participants | 555 Participants |
| Sex: Female, Male Male | 2 Participants | 0 Participants | 2 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 149 / 373 | 90 / 184 |
| other Total, other adverse events | 366 / 371 | 167 / 172 |
| serious Total, serious adverse events | 103 / 371 | 43 / 172 |
Outcome results
Primary
Progression-free Survival (PFS) Based on Blinded Independent Central Review (BICR) in the Hormone Receptor-Positive Cohort in Participants With HER2-low Breast Cancer
Progression-free survival (PFS), defined as at least a 20% increase in the sum of diameters of target lesions, was assessed from the date of randomization to the date of the first radiographic disease progression or death due to any cause, whichever came first. PFS was based on blinded independent central review (BICR) in the hormone receptor-positive cohort according to modified Response Evaluation Criteria in Solid Tumors (mRECIST) version 1.1. Median PFS was from Kaplan-Meier analysis. Confidence interval for median was computed using the Brookmeyer-Crowley method.
Time frame: From the date of randomization to the earliest date of the first objective documentation of radiographic disease progression or death due to any cause, up to approximately 3 years
Population: Progression-free survival (PFS) was assessed in the Hormone Receptor-Positive cohort of Full Analysis Set.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Trastuzumab Deruxtecan (T-DXd) | Progression-free Survival (PFS) Based on Blinded Independent Central Review (BICR) in the Hormone Receptor-Positive Cohort in Participants With HER2-low Breast Cancer | 10.1 months |
| Physician's Choice | Progression-free Survival (PFS) Based on Blinded Independent Central Review (BICR) in the Hormone Receptor-Positive Cohort in Participants With HER2-low Breast Cancer | 5.4 months |
p-value: <0.000195% CI: [0.4012, 0.6444]Log Rank
Secondary
Best Overall Response and Confirmed Objective Response Rate (ORR) in Participants With HER2-low Breast Cancer (All Patients)
Best overall response rate and confirmed objective response rate (ORR) were assessed by blinded independent central review (BICR) and investigator assessment. Complete response (CR) was defined as a disappearance of all target lesions, partial response (PR) was defined as at least a 30% decrease in the sum of diameters of target lesions, and stable disease (SD) was defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease (PD; at least a 20% increase in the sum of diameters of target lesions. Confirmed ORR was defined as the number of participants with complete and partial responses and confirmed by a second assessment.
Time frame: From screening and every 6 weeks up to withdrawal of subject consent, progressive disease (PD), or unacceptable toxicity, up to approximately 3 years
Population: Best overall response and confirmed objective response rate were assessed in the Full Analysis Set.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Trastuzumab Deruxtecan (T-DXd) | Best Overall Response and Confirmed Objective Response Rate (ORR) in Participants With HER2-low Breast Cancer (All Patients) | BICR: Partial response | 183 Participants |
| Trastuzumab Deruxtecan (T-DXd) | Best Overall Response and Confirmed Objective Response Rate (ORR) in Participants With HER2-low Breast Cancer (All Patients) | Investigator: Partial response | 187 Participants |
| Trastuzumab Deruxtecan (T-DXd) | Best Overall Response and Confirmed Objective Response Rate (ORR) in Participants With HER2-low Breast Cancer (All Patients) | BICR: Progressive disease | 31 Participants |
| Trastuzumab Deruxtecan (T-DXd) | Best Overall Response and Confirmed Objective Response Rate (ORR) in Participants With HER2-low Breast Cancer (All Patients) | Investigator: Stable disease | 135 Participants |
| Trastuzumab Deruxtecan (T-DXd) | Best Overall Response and Confirmed Objective Response Rate (ORR) in Participants With HER2-low Breast Cancer (All Patients) | BICR: Not evaluable | 17 Participants |
| Trastuzumab Deruxtecan (T-DXd) | Best Overall Response and Confirmed Objective Response Rate (ORR) in Participants With HER2-low Breast Cancer (All Patients) | Investigator: Progressive disease | 32 Participants |
| Trastuzumab Deruxtecan (T-DXd) | Best Overall Response and Confirmed Objective Response Rate (ORR) in Participants With HER2-low Breast Cancer (All Patients) | BICR: Stable disease | 129 Participants |
| Trastuzumab Deruxtecan (T-DXd) | Best Overall Response and Confirmed Objective Response Rate (ORR) in Participants With HER2-low Breast Cancer (All Patients) | Investigator: Not evaluable | 13 Participants |
| Trastuzumab Deruxtecan (T-DXd) | Best Overall Response and Confirmed Objective Response Rate (ORR) in Participants With HER2-low Breast Cancer (All Patients) | BICR: Confirmed Objective response rate | 195 Participants |
| Trastuzumab Deruxtecan (T-DXd) | Best Overall Response and Confirmed Objective Response Rate (ORR) in Participants With HER2-low Breast Cancer (All Patients) | Investigator: Complete response | 6 Participants |
| Trastuzumab Deruxtecan (T-DXd) | Best Overall Response and Confirmed Objective Response Rate (ORR) in Participants With HER2-low Breast Cancer (All Patients) | Investigator: Confirmed Objective response rate | 193 Participants |
| Trastuzumab Deruxtecan (T-DXd) | Best Overall Response and Confirmed Objective Response Rate (ORR) in Participants With HER2-low Breast Cancer (All Patients) | BICR: Complete response | 13 Participants |
| Physician's Choice | Best Overall Response and Confirmed Objective Response Rate (ORR) in Participants With HER2-low Breast Cancer (All Patients) | Investigator: Confirmed Objective response rate | 31 Participants |
| Physician's Choice | Best Overall Response and Confirmed Objective Response Rate (ORR) in Participants With HER2-low Breast Cancer (All Patients) | BICR: Progressive disease | 41 Participants |
| Physician's Choice | Best Overall Response and Confirmed Objective Response Rate (ORR) in Participants With HER2-low Breast Cancer (All Patients) | Investigator: Not evaluable | 20 Participants |
| Physician's Choice | Best Overall Response and Confirmed Objective Response Rate (ORR) in Participants With HER2-low Breast Cancer (All Patients) | BICR: Complete response | 2 Participants |
| Physician's Choice | Best Overall Response and Confirmed Objective Response Rate (ORR) in Participants With HER2-low Breast Cancer (All Patients) | BICR: Partial response | 28 Participants |
| Physician's Choice | Best Overall Response and Confirmed Objective Response Rate (ORR) in Participants With HER2-low Breast Cancer (All Patients) | BICR: Stable disease | 91 Participants |
| Physician's Choice | Best Overall Response and Confirmed Objective Response Rate (ORR) in Participants With HER2-low Breast Cancer (All Patients) | BICR: Not evaluable | 22 Participants |
| Physician's Choice | Best Overall Response and Confirmed Objective Response Rate (ORR) in Participants With HER2-low Breast Cancer (All Patients) | Investigator: Complete response | 0 Participants |
| Physician's Choice | Best Overall Response and Confirmed Objective Response Rate (ORR) in Participants With HER2-low Breast Cancer (All Patients) | Investigator: Partial response | 31 Participants |
| Physician's Choice | Best Overall Response and Confirmed Objective Response Rate (ORR) in Participants With HER2-low Breast Cancer (All Patients) | Investigator: Stable disease | 93 Participants |
| Physician's Choice | Best Overall Response and Confirmed Objective Response Rate (ORR) in Participants With HER2-low Breast Cancer (All Patients) | Investigator: Progressive disease | 40 Participants |
| Physician's Choice | Best Overall Response and Confirmed Objective Response Rate (ORR) in Participants With HER2-low Breast Cancer (All Patients) | BICR: Confirmed Objective response rate | 30 Participants |
Secondary
Best Overall Response and Confirmed Objective Response Rate (ORR) in the Hormone Receptor-Positive Cohort in Participants With HER2-low Breast Cancer
Best overall response rate and confirmed objective response rate (ORR) were assessed by blinded independent central review (BICR) and investigator assessment. Complete response (CR) was defined as a disappearance of all target lesions, partial response (PR) was defined as at least a 30% decrease in the sum of diameters of target lesions, and stable disease (SD) was defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease (PD; at least a 20% increase in the sum of diameters of target lesions. Confirmed ORR was defined as the number of participants with complete and partial responses and confirmed by a second assessment.
Time frame: From screening and every 6 weeks up to withdrawal of subject consent, progressive disease (PD), or unacceptable toxicity, up to approximately 3 years
Population: Best overall response and confirmed objective response rate were assessed in the Hormone Receptor-Positive cohort of Full Analysis Set.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Trastuzumab Deruxtecan (T-DXd) | Best Overall Response and Confirmed Objective Response Rate (ORR) in the Hormone Receptor-Positive Cohort in Participants With HER2-low Breast Cancer | Investigator: Partial response | 163 Participants |
| Trastuzumab Deruxtecan (T-DXd) | Best Overall Response and Confirmed Objective Response Rate (ORR) in the Hormone Receptor-Positive Cohort in Participants With HER2-low Breast Cancer | BICR: Complete response | 12 Participants |
| Trastuzumab Deruxtecan (T-DXd) | Best Overall Response and Confirmed Objective Response Rate (ORR) in the Hormone Receptor-Positive Cohort in Participants With HER2-low Breast Cancer | BICR: Partial response | 164 Participants |
| Trastuzumab Deruxtecan (T-DXd) | Best Overall Response and Confirmed Objective Response Rate (ORR) in the Hormone Receptor-Positive Cohort in Participants With HER2-low Breast Cancer | BICR: Stable disease | 115 Participants |
| Trastuzumab Deruxtecan (T-DXd) | Best Overall Response and Confirmed Objective Response Rate (ORR) in the Hormone Receptor-Positive Cohort in Participants With HER2-low Breast Cancer | BICR: Progressive disease | 26 Participants |
| Trastuzumab Deruxtecan (T-DXd) | Best Overall Response and Confirmed Objective Response Rate (ORR) in the Hormone Receptor-Positive Cohort in Participants With HER2-low Breast Cancer | BICR: Not evaluable | 14 Participants |
| Trastuzumab Deruxtecan (T-DXd) | Best Overall Response and Confirmed Objective Response Rate (ORR) in the Hormone Receptor-Positive Cohort in Participants With HER2-low Breast Cancer | Investigator: Complete response | 5 Participants |
| Trastuzumab Deruxtecan (T-DXd) | Best Overall Response and Confirmed Objective Response Rate (ORR) in the Hormone Receptor-Positive Cohort in Participants With HER2-low Breast Cancer | Investigator: Stable disease | 124 Participants |
| Trastuzumab Deruxtecan (T-DXd) | Best Overall Response and Confirmed Objective Response Rate (ORR) in the Hormone Receptor-Positive Cohort in Participants With HER2-low Breast Cancer | Investigator: Progressive disease | 28 Participants |
| Trastuzumab Deruxtecan (T-DXd) | Best Overall Response and Confirmed Objective Response Rate (ORR) in the Hormone Receptor-Positive Cohort in Participants With HER2-low Breast Cancer | Investigator: Not evaluable | 11 Participants |
| Trastuzumab Deruxtecan (T-DXd) | Best Overall Response and Confirmed Objective Response Rate (ORR) in the Hormone Receptor-Positive Cohort in Participants With HER2-low Breast Cancer | BICR: Confirmed Objective response rate | 175 Participants |
| Trastuzumab Deruxtecan (T-DXd) | Best Overall Response and Confirmed Objective Response Rate (ORR) in the Hormone Receptor-Positive Cohort in Participants With HER2-low Breast Cancer | Investigator: Confirmed Objective response rate | 168 Participants |
| Physician's Choice | Best Overall Response and Confirmed Objective Response Rate (ORR) in the Hormone Receptor-Positive Cohort in Participants With HER2-low Breast Cancer | Investigator: Progressive disease | 34 Participants |
| Physician's Choice | Best Overall Response and Confirmed Objective Response Rate (ORR) in the Hormone Receptor-Positive Cohort in Participants With HER2-low Breast Cancer | BICR: Confirmed Objective response rate | 27 Participants |
| Physician's Choice | Best Overall Response and Confirmed Objective Response Rate (ORR) in the Hormone Receptor-Positive Cohort in Participants With HER2-low Breast Cancer | Investigator: Complete response | 0 Participants |
| Physician's Choice | Best Overall Response and Confirmed Objective Response Rate (ORR) in the Hormone Receptor-Positive Cohort in Participants With HER2-low Breast Cancer | BICR: Complete response | 1 Participants |
| Physician's Choice | Best Overall Response and Confirmed Objective Response Rate (ORR) in the Hormone Receptor-Positive Cohort in Participants With HER2-low Breast Cancer | Investigator: Partial response | 30 Participants |
| Physician's Choice | Best Overall Response and Confirmed Objective Response Rate (ORR) in the Hormone Receptor-Positive Cohort in Participants With HER2-low Breast Cancer | BICR: Partial response | 26 Participants |
| Physician's Choice | Best Overall Response and Confirmed Objective Response Rate (ORR) in the Hormone Receptor-Positive Cohort in Participants With HER2-low Breast Cancer | Investigator: Confirmed Objective response rate | 30 Participants |
| Physician's Choice | Best Overall Response and Confirmed Objective Response Rate (ORR) in the Hormone Receptor-Positive Cohort in Participants With HER2-low Breast Cancer | BICR: Stable disease | 81 Participants |
| Physician's Choice | Best Overall Response and Confirmed Objective Response Rate (ORR) in the Hormone Receptor-Positive Cohort in Participants With HER2-low Breast Cancer | Investigator: Stable disease | 80 Participants |
| Physician's Choice | Best Overall Response and Confirmed Objective Response Rate (ORR) in the Hormone Receptor-Positive Cohort in Participants With HER2-low Breast Cancer | BICR: Progressive disease | 34 Participants |
| Physician's Choice | Best Overall Response and Confirmed Objective Response Rate (ORR) in the Hormone Receptor-Positive Cohort in Participants With HER2-low Breast Cancer | Investigator: Not evaluable | 19 Participants |
| Physician's Choice | Best Overall Response and Confirmed Objective Response Rate (ORR) in the Hormone Receptor-Positive Cohort in Participants With HER2-low Breast Cancer | BICR: Not evaluable | 21 Participants |
Secondary
Duration of Response in Participants With HER2-low Breast Cancer (All Patients)
Duration of Response (DoR) is defined as the date of the first documented objective response (complete response \[CR\] or partial response \[PR\]) to the first documented disease progression or death, whichever occurs first. DoR was based on blinded independent central review (BICR) and investigator assessment. Median was from Kaplan-Meier estimate. Confidence interval for median was computed using the Brookmeyer-Crowley method.
Time frame: From the date of the first documented objective response (CR or PR) to the first documented disease progression or death, whichever occurs first, up to approximately 3 years
Population: Duration of response was assessed in the Full Analysis Set.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Trastuzumab Deruxtecan (T-DXd) | Duration of Response in Participants With HER2-low Breast Cancer (All Patients) | BICR: DoR | 10.7 months |
| Trastuzumab Deruxtecan (T-DXd) | Duration of Response in Participants With HER2-low Breast Cancer (All Patients) | Investigator: DoR | 8.3 months |
| Physician's Choice | Duration of Response in Participants With HER2-low Breast Cancer (All Patients) | BICR: DoR | 6.8 months |
| Physician's Choice | Duration of Response in Participants With HER2-low Breast Cancer (All Patients) | Investigator: DoR | 5.6 months |
Secondary
Duration of Response in the Hormone Receptor-Positive Cohort in Participants With HER2-low Breast Cancer
Duration of Response (DoR) is defined as the date of the first documented objective response (complete response \[CR\] or partial response \[PR\]) to the first documented disease progression or death, whichever occurs first. DoR was based on blinded independent central review (BICR) and investigator assessment. Median was from Kaplan-Meier estimate. Confidence interval for median was computed using the Brookmeyer-Crowley method.
Time frame: From the date of the first documented objective response (CR or PR) to the first documented disease progression or death, whichever occurs first, up to approximately 3 years
Population: Duration of response was assessed in the Hormone Receptor-Positive cohort of Full Analysis Set.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Trastuzumab Deruxtecan (T-DXd) | Duration of Response in the Hormone Receptor-Positive Cohort in Participants With HER2-low Breast Cancer | BICR: DoR | 10.7 months |
| Trastuzumab Deruxtecan (T-DXd) | Duration of Response in the Hormone Receptor-Positive Cohort in Participants With HER2-low Breast Cancer | Investigator: DoR | 8.3 months |
| Physician's Choice | Duration of Response in the Hormone Receptor-Positive Cohort in Participants With HER2-low Breast Cancer | BICR: DoR | 6.8 months |
| Physician's Choice | Duration of Response in the Hormone Receptor-Positive Cohort in Participants With HER2-low Breast Cancer | Investigator: DoR | 5.6 months |
Secondary
Number of Overall Survival Events (Deaths)
Time frame: From the date of randomization up to the date of death due to any cause, up to approximately 3 years
Population: Overall survival events (deaths) were analyzed in the Full Analysis Set (defined as all randomized participants).
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Trastuzumab Deruxtecan (T-DXd) | Number of Overall Survival Events (Deaths) | 149 events (deaths) |
| Physician's Choice | Number of Overall Survival Events (Deaths) | 90 events (deaths) |
Secondary
Overall Survival (OS) in All Patients
Overall survival (OS) was defined as the time from the date of randomization to the date of death due to any cause. If there was no death reported for a participant before the data cutoff for OS analysis, OS was censored at the last contact date at which the participant was known to be alive.
Time frame: From the date of randomization up to the date of death due to any cause, up to approximately 3 years
Population: Overall survival (OS) was assessed in the Full Analysis Set (defined as all randomized participants).
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Trastuzumab Deruxtecan (T-DXd) | Overall Survival (OS) in All Patients | 23.4 months |
| Physician's Choice | Overall Survival (OS) in All Patients | 16.8 months |
Secondary
Overall Survival (OS) in the Hormone Receptor-Positive Cohort in Participants With HER2-low Breast Cancer
Overall survival (OS) was defined as the time from the date of randomization to the date of death due to any cause. If there was no death reported for a participant before the data cutoff for OS analysis, OS was censored at the last contact date at which the participant was known to be alive.
Time frame: From the date of randomization up to the date of death due to any cause, up to approximately 3 years
Population: Overall survival (OS) was assessed in the Hormone Receptor-Positive cohort of Full Analysis Set.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Trastuzumab Deruxtecan (T-DXd) | Overall Survival (OS) in the Hormone Receptor-Positive Cohort in Participants With HER2-low Breast Cancer | 23.9 months |
| Physician's Choice | Overall Survival (OS) in the Hormone Receptor-Positive Cohort in Participants With HER2-low Breast Cancer | 17.5 months |
Secondary
Progression-free Survival Based on Investigator Assessment in Participants With HER2-low Breast Cancer (All Patients)
Progression-free survival (PFS), defined as at least a 20% increase in the sum of diameters of target lesions, was assessed from the date of randomization to the date of the first radiographic disease progression or death due to any cause, whichever came first. PFS was based on investigator assessment according to modified Response Evaluation Criteria in Solid Tumors (mRECIST) version 1.1. Median PFS was from Kaplan-Meier analysis. Confidence interval for median was computed using the Brookmeyer-Crowley method.
Time frame: From the date of randomization to the earliest date of the first objective documentation of radiographic disease progression or death due to any cause, up to approximately 3 years
Population: Progression-free survival (PFS) was assessed in the Full Analysis Set.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Trastuzumab Deruxtecan (T-DXd) | Progression-free Survival Based on Investigator Assessment in Participants With HER2-low Breast Cancer (All Patients) | 8.8 months |
| Physician's Choice | Progression-free Survival Based on Investigator Assessment in Participants With HER2-low Breast Cancer (All Patients) | 4.2 months |
Secondary
Progression-free Survival Based on Investigator Assessment in the Hormone Receptor-Positive Cohort in Participants With HER2-low Breast Cancer
Progression-free survival (PFS), defined as at least a 20% increase in the sum of diameters of target lesions, was assessed from the date of randomization to the date of the first radiographic disease progression or death due to any cause, whichever came first. PFS was based on investigator assessment in the hormone receptor-positive cohort according to modified Response Evaluation Criteria in Solid Tumors (mRECIST) version 1.1. Median PFS was from Kaplan-Meier analysis. Confidence interval for median was computed using the Brookmeyer-Crowley method.
Time frame: From the date of randomization to the earliest date of the first objective documentation of radiographic disease progression or death due to any cause, up to approximately 3 years
Population: Progression-free survival (PFS) was assessed in the Hormone Receptor-Positive cohort of Full Analysis Set.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Trastuzumab Deruxtecan (T-DXd) | Progression-free Survival Based on Investigator Assessment in the Hormone Receptor-Positive Cohort in Participants With HER2-low Breast Cancer | 9.6 months |
| Physician's Choice | Progression-free Survival Based on Investigator Assessment in the Hormone Receptor-Positive Cohort in Participants With HER2-low Breast Cancer | 4.2 months |
Secondary
Progression-free Survival (PFS) Based on Blinded Independent Central Review (BICR) in Participants With HER2-low Breast Cancer (All Patients) Regardless of Hormone Receptor Status
Progression-free survival (PFS), defined as at least a 20% increase in the sum of diameters of target lesions, was assessed from the date of randomization to the date of the first radiographic disease progression or death due to any cause, whichever came first. PFS was based on blinded independent central review (BICR) according to modified Response Evaluation Criteria in Solid Tumors (mRECIST) version 1.1. Median PFS was from Kaplan-Meier analysis. Confidence interval for median was computed using the Brookmeyer-Crowley method.
Time frame: From the date of randomization to the earliest date of the first objective documentation of radiographic disease progression or death due to any cause, up to approximately 3 years
Population: Progression-free survival (PFS) was assessed in the Full Analysis Set.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Trastuzumab Deruxtecan (T-DXd) | Progression-free Survival (PFS) Based on Blinded Independent Central Review (BICR) in Participants With HER2-low Breast Cancer (All Patients) Regardless of Hormone Receptor Status | 9.9 months |
| Physician's Choice | Progression-free Survival (PFS) Based on Blinded Independent Central Review (BICR) in Participants With HER2-low Breast Cancer (All Patients) Regardless of Hormone Receptor Status | 5.1 months |
Other Pre-specified
All-Cause Mortality
All-cause mortality is defined as all anticipated and unanticipated deaths due to any cause, with the number and frequency of such events by arm or comparison group of the clinical study.
Time frame: From the date of randomization up to the date of death due to any cause, up to approximately 3 years
Population: All-cause mortality was assessed in the Safety Analysis Set.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Trastuzumab Deruxtecan (T-DXd) | All-Cause Mortality | 148 Participants |
| Physician's Choice | All-Cause Mortality | 88 Participants |