Advanced or Metastatic Breast Cancer
Conditions
Keywords
Breast Cancer, HR positive, HER2-Low, HER2-Negative, Trastuzumab Deruxtecan (T-DXd; DS-8201a), Anti-HER2-Antibody Drug Conjugate (ADC), DESTINY-Breast06
Brief summary
This study will evaluate the efficacy, safety and tolerability of trastuzumab deruxtecan compared with investigator's choice chemotherapy in human epidermal growth factor receptor (HER)2-low, hormone receptor (HR) positive breast cancer patients whose disease has progressed on endocrine therapy in the metastatic setting.
Detailed description
Eligible patients will be those patients who have had disease progression on at least 2 previous lines of endocrine therapies given for the treatment of metastatic disease or disease progression within 6 months of starting first line treatment for metastatic disease with an endocrine therapy combined with a CDK4/6 inhibitor. All patients must have historically confirmed HR positive (either estrogen receptor and/or progesterone receptor positive), HER2-low (defined as IHC2+/ISH- and IHC 1+) or HER2 IHC \>0 \<1+ expression, as determined by central laboratory testing results, advanced or metastatic breast cancer. The study aims to evaluate the efficacy, safety and tolerability of trastuzumab deruxtecan compared with investigator's choice chemotherapy. This study aims to see if trastuzumab deruxtecan allows patients to live longer without the cancer getting worse, or simply to live longer, compared to patients receiving standard of care chemotherapy. This study is also looking to see how the treatment and the cancer affects patients' quality of life.
Interventions
DRUGTrastuzumab deruxtecan
Trastuzumab deruxtecan by intravenous infusion
DRUGCapecitabine
Investigator's choice standard of care single agent chemotherapy; capecitabine tablets will be given orally.
DRUGPaclitaxel
Investigator's choice standard of care single agent chemotherapy; paclitaxel by intravenous infusion.
DRUGNab-Paclitaxel
Investigator's choice standard of care single agent chemotherapy; nab-paclitaxel by intravenous infusion
Sponsors
AstraZeneca
Daiichi Sankyo
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Masking description
This study is an open-label study that will be conducted "Sponsor-blind". To maintain the integrity of the study, Sponsor personnel directly involved in study conduct will not undertake or have access to efficacy data aggregated by treatment group prior to final data readout for the primary endpoint.
Intervention model description
The study consists of 2 independent open label treatment arms: trastuzumab deruxtecan and Investigator's choice chemotherapy (paclitaxel, nab-paclitaxel or capecitabine).
Eligibility
Sex/Gender
ALL
Age
18 Years to 105 Years
Healthy volunteers
No
Inclusion criteria
Key Inclusion Criteria: * Patients must be ≥18 years of age * Pathologically documented breast cancer that: 1. is advanced or metastatic 2. has a history of HER2-low or negative expression by local test, defined as IHC 2+/ISH- or IHC 1+ (ISH- or untested) or HER2 IHC 0 (ISH- or untested) 3. has HER2-low or HER2 IHC \>0 \<1+ expression as determined by the central laboratory result established on a tissue sample taken in the metastatic setting 4. was never previously HER2-positive 5. is documented HR+ disease in the metastatic setting. * No prior chemotherapy for advanced or metastatic breast cancer. * Has adequate tumor samples for assessment of HER2 status * Must have either: 1. disease progression within 6 months of starting first line metastatic treatment with an endocrine therapy combined with a CDK4/6 inhibitor or 2. disease progression on at least 2 previous lines of endocrine therapy with or without a targeted therapy in the metastatic setting. Of note with regards to the ≥2 lines of previous ET requirement: disease recurrence while on the first 24 months of starting adjuvant ET, will be considered a line of therapy; these patients will only require 1 line of ET in the metastatic setting. * Has protocol-defined adequate organ and bone marrow function Key
Exclusion criteria
* Ineligible for all options in the investigator's choice chemotherapy arm * Lung-specific intercurrent clinically significant illnesses * Uncontrolled or significant cardiovascular disease or infection * Prior documented interstitial lung disease (ILD)/ pneumonitis that required steroids, current ILD/ pneumonitis, or suspected ILD/ pneumonitis that cannot be ruled out by imaging at screening. * Patients with spinal cord compression or clinically active central nervous system metastases * Prior randomization or treatment in a previous trastuzumab deruxtecan study regardless of treatment arm assignment * Concurrent enrolment in another clinical study, unless it is an observational (non-interventional) clinical study during the follow up period of a prior interventional study (prescreening for this study while a patient is on treatment in another clinical study is acceptable)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Progression-Free Survival (PFS) Assessed by Blinded Independent Central Review (BICR) in the Hormone Receptor-Positive (HR+), Human Epidermal Growth Factor Receptor 2 (HER2)-Low Population | Response evaluations performed at screening, every 6 weeks (q6w) ± 1 week from randomization for 48 weeks, and then every 9 weeks (q9w) ± 1 week, starting at Week 48 until PD, up to PCD of 18 March 2024 (maximum of approximately 43.85 months) | PFS per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1) assessed by BICR was defined as the time from the date of randomization until the date of PD, as defined or death (by any cause in the absence of progression) regardless of whether the participant withdrew from randomized therapy or received another anticancer therapy prior to progression. PD was defined as at least a 20% increase in the sum of diameters of target lesions (TLs), taking as reference the smallest previous sum of diameters (nadir), this included the baseline sum if that was the smallest on study. In addition to the relative increase of 20%, the sum must demonstrate an absolute increase of at least 5 millimeter (mm) from nadir. Median PFS was calculated using Kaplan-Meier method and its confidence interval (CI) using Brookmeyer-Crowley method. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Overall Survival (OS) in the Hormone Receptor-Positive, Human Epidermal Growth Factor Receptor 2-low Population | From date of randomization until death due to any cause, up to PCD of 18 March 2024 (maximum of approximately 43.85 months) | OS was defined as the time from the date of randomization until death due to any cause regardless of whether the participant withdrew from randomized therapy or received another anticancer therapy. Median OS was calculated using Kaplan-Meier method and its CI using Brookmeyer-Crowley method. |
| Progression-Free Survival Assessed by Blinded Independent Central Review in the Intent-to-Treat, Human Epidermal Growth Factor Receptor 2 Immunohistochemistry (IHC) >0 <1+ and Human Epidermal Growth Factor Receptor 2-low Population | Response evaluations performed at screening, q6w ± 1 week from randomization for 48 weeks, and then q9w ± 1 week, starting at Week 48 until PD, up to PCD of 18 March 2024 (maximum of approximately 43.85 months) | PFS per RECIST 1.1 assessed by BICR was defined as the time from the date of randomization until the date of PD, as defined or death (by any cause in the absence of progression) regardless of whether the participant withdrew from randomized therapy or received another anticancer therapy prior to progression. PD was defined as at least a 20% increase in the sum of diameters of TLs, taking as reference the smallest previous sum of diameters (nadir), this included the baseline sum if that was the smallest on study. In addition to the relative increase of 20%, the sum must demonstrate an absolute increase of at least 5 mm from nadir. Median PFS was calculated using Kaplan-Meier method and its CI using Brookmeyer-Crowley method. |
| Overall Survival (OS) in the Intent-to-Treat Population | From date of randomization until death due to any cause, up to PCD of 18 March 2024 (maximum of approximately 43.85 months) | OS was defined as the time from the date of randomization until death due to any cause regardless of whether the participant withdrew from randomized therapy or received another anticancer therapy. Median OS was calculated using Kaplan-Meier method and its CI using Brookmeyer-Crowley method. |
| Progression-Free Survival Assessed by Investigator in the Hormone Receptor-Positive, Human Epidermal Growth Factor Receptor 2-low Population | Response evaluations performed at screening, q6w ± 1 week from randomization for 48 weeks, and then q9w ± 1 week, starting at Week 48 until PD, up to PCD of 18 March 2024 (maximum of approximately 43.85 months) | PFS per RECIST 1.1 assessed by Investigator was defined as the time from the date of randomization until the date of PD, as defined or death (by any cause in the absence of progression) regardless of whether the participant withdrew from randomized therapy or received another anticancer therapy prior to progression. PD was defined as at least a 20% increase in the sum of diameters of TLs, taking as reference the smallest previous sum of diameters (nadir), this included the baseline sum if that was the smallest on study. In addition to the relative increase of 20%, the sum must demonstrate an absolute increase of at least 5 mm from nadir. Median PFS was calculated using Kaplan-Meier method and its CI using Brookmeyer-Crowley method. |
| Objective Response Rate (ORR) Assessed by Blinded Independent Central Review and Investigator in the Hormone Receptor-Positive, Human Epidermal Growth Factor Receptor 2-low Population | Response evaluations performed at screening, q6w ± 1 week from randomization for 48 weeks, and then q9w ± 1 week, starting at Week 48 until PD, up to PCD of 18 March 2024 (maximum of approximately 43.85 months) | ORR per RECIST 1.1 assessed by BICR and Investigator was defined as the percentage of participants with at least 1 visit response of complete response (CR) or partial response (PR). CR was defined as disappearance of all TLs since baseline. Any pathological lymph nodes selected as TLs must have a reduction in short axis diameter to \<10 mm. PR was defined as at least a 30% decrease in the sum of the diameters of TL, taking as reference the baseline sum of diameters. |
| Duration of Response (DOR) Assessed by Blinded Independent Central Review and Investigator in the Hormone Receptor-Positive, Human Epidermal Growth Factor Receptor 2-low Population | Response evaluations performed at screening, q6w ± 1 week from randomization for 48 weeks, and then q9w ± 1 week, starting at Week 48 until PD, up to PCD of 18 March 2024 (maximum of approximately 43.85 months) | DOR per RECIST v1.1 was defined as the time from the date of first documented response until date of documented progression or death in the absence of PD. PD was defined as at least a 20% increase in the sum of diameters of TLs, taking as reference the smallest previous sum of diameters (nadir), this included the baseline sum if that was the smallest on study. In addition to the relative increase of 20%, the sum must demonstrate an absolute increase of at least 5 mm from nadir. Median DOR was calculated using Kaplan-Meier method. |
| Objective Response Rate Assessed by Blinded Independent Central Review and Investigator in the Intent-to-Treat and Human Epidermal Growth Factor Receptor 2 Immunohistochemistry >0 <1+ Population | Response evaluations performed at screening, q6w ± 1 week from randomization for 48 weeks, and then q9w ± 1 week, starting at Week 48 until PD, up to PCD of 18 March 2024 (maximum of approximately 43.85 months) | ORR per RECIST 1.1 assessed by BICR and Investigator was defined as the percentage of participants with at least 1 visit response of CR or PR. CR was defined as disappearance of all TLs since baseline. Any pathological lymph nodes selected as TLs must have a reduction in short axis diameter to \<10 mm. PR was defined as at least a 30% decrease in the sum of the diameters of TL, taking as reference the baseline sum of diameters. |
| Duration of Response Assessed by Blinded Independent Central Review and Investigator in the Intent-to-Treat Population | Response evaluations performed at screening, q6w ± 1 week from randomization for 48 weeks, and then q9w ± 1 week, starting at Week 48 until PD, up to PCD of 18 March 2024 (maximum of approximately 43.85 months) | DOR per RECIST v1.1 was defined as the time from the date of first documented response until date of documented progression or death in the absence of PD. PD was defined as at least a 20% increase in the sum of diameters of TLs, taking as reference the smallest previous sum of diameters (nadir), this included the baseline sum if that was the smallest on study. In addition to the relative increase of 20%, the sum must demonstrate an absolute increase of at least 5 mm from nadir. Median DOR was calculated using Kaplan-Meier method. |
| Time From Randomization to Second Progression or Death (PFS2) in the Hormone Receptor-Positive, Human Epidermal Growth Factor Receptor 2-low and Intent-to-Treat Population | Response evaluations performed at screening, q6w ± 1 week from randomization for 48 weeks, and then q9w ± 1 week, starting at Week 48 until PD, up to PCD of 18 March 2024 (maximum of approximately 43.85 months) | PFS2 was defined as time from randomization to second progression (the earliest of the progression event subsequent to first subsequent therapy) or death; second progression was defined according to local standard clinical practice and might involve any of the following: objective radiological imaging, symptomatic progression, or death. Median PFS2 was calculated using Kaplan-Meier method and its CI using Brookmeyer-Crowley method. |
| Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Treatment-Emergent Serious Adverse Events (TESAEs) | From first dose of study drug (Day 1) up to PCD of 18 March 2024 (maximum of approximately 43.85 months) | An adverse event (AE) was any untoward medical occurrence in a participant or clinical study participant administered a medicinal product and which did not necessarily had a causal relationship with this treatment. A serious adverse event (SAE) was an AE occurring during any study phase, that fulfilled 1 or more of following criteria: resulted in death, was immediately life-threatening, required in-participant hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability or incapacity, was congenital abnormality or birth defect, and was an important medical event that jeopardized participant or required medical treatment to prevent 1 of outcomes listed above. TEAE was any AE that occurred, having been absent before the first dose of study drug, or had worsened in severity or seriousness after initiation of the study drug until the 40-day (+7 days) safety follow-up visit. |
| Serum Concentration of Trastuzumab Deruxtecan (T-DXd), Total Anti-Human Epidermal Growth Factor Receptor 2 Antibody and MAAA-1181a | Pre-dose on Day 1 of Cycles 1, 2, 4, 6 and 8; 15 minutes post-dose on Day 1 of Cycles 1, 2 and 4; and 5 hours post-dose on Day 1 of Cycle 1 (each cycle is 21 days) | Blood samples were collected at indicated time points to determine the concentration of T-DXd, total anti-HER2 antibody and MAAA-1181a in serum. |
| Change From Baseline in European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) Scale Score at Week 91 | Baseline (Day 1) and Week 91 | EORTC QLQ-C30 is a 30-item self-administered questionnaire grouped into 5 multi-item functional scales(physical,role,emotional,cognitive and social),3 multiitem symptom scales(fatigue,pain and nausea/vomiting),2-item global QoL scale,5 single items assessing additional symptoms reported by cancer participants(dyspnea,loss of appetite,insomnia,constipation and diarrhea). All but 2 questions have 4-point scales:1:not at all,2:a little,3:quite a bit,4:very much.2 questions concerning global health status and QoL have 7-point scales with responses ranging from 1:very poor to 7:excellent;higher score:better level of functioning/greater degree of symptoms.For each of 15 scales,final scores were averaged from scores of component items,transformed,range: 0 to 100;higher scores:better functioning,better health related (HR)QoL,or greater level of symptoms(higher scores:opposite interpretations for functioning/QoL and symptoms/problems).Baseline:last observed measurement prior to randomization. |
| Change From Baseline in European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire-Breast Module 45 (BR45) Scale Score at Week 58 | Baseline (Day 1) and Week 58 | EORTC QLQ-BR45 is an updated version of the BR23. Self-administered instrument includes original 23-items yielding 5 multi-item scores (body image, sexual functioning, arm symptoms, breast symptoms, and systemic therapy side effects). Additional 22 items yield 4 additional multi-item scales (breast satisfaction, endocrine therapy symptoms, skin mucosis symptoms, and endocrine sexual symptoms). Single items assess sexual enjoyment, future perspective and being upset by hair loss. Items are scored on a 4-point verbal rating scale: 1: not at all, 2: a little, 3: quite a bit, and 4: very much; higher score: better level of functioning or greater degree of symptoms. Scores of these scales were averaged from scores of component items, transformed, and ranged from 0 to 100; higher scores for functioning scales or items indicate better functioning, whereas higher scores for symptom scales or items represent a higher level of symptoms. Baseline:last observed measurement prior to randomization. |
| Time to Deterioration in European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 Scale Score | From randomization until date of first symptom deterioration that is confirmed, up to PCD of 18 March 2024 (maximum of approximately 43.85 months) | Time to deterioration was defined as the time from randomization until the date of the first clinically meaningful deterioration that was confirmed at next available assessment, at least 14 days apart, regardless of whether the participant withdrew from study treatment or receives another anti-cancer therapy prior to deterioration. |
| Number of Participants With Anti-Drug Antibodies (ADAs) Against Trastuzumab Deruxtecan | From Day 1 up to PCD of 18 March 2024 (maximum of approximately 43.85 months) | Blood samples were collected at indicated timepoints to determine ADA. Treatment-induced ADA was defined as ADA positive post-baseline and not detected at baseline (negative or missing). Treatment-boosted ADA was defined as a baseline positive ADA titer that was boosted to a 4-fold or higher-level following drug administration. |
| Time to First Subsequent Treatment or Death (TFST) in the Hormone Receptor-Positive, Human Epidermal Growth Factor Receptor 2-low and Intent-to-Treat Population | From Day 1 up to 64 months | TFST was defined as time from randomization to the start date of the first subsequent anti-cancer therapy after discontinuation of randomized treatment or death due to any cause. |
| Time to Second Subsequent Treatment or Death (TSST) in the Hormone Receptor-Positive, Human Epidermal Growth Factor Receptor 2-low and Intent-to-Treat Population | From Day 1 up to 64 months | TSST was defined as time from randomization to the start date of the second subsequent anti-cancer therapy after discontinuation of randomized treatment or death due to any cause. |
Countries
Argentina, Australia, Austria, Belgium, Brazil, Canada, China, Denmark, France, Germany, Hungary, India, Israel, Italy, Japan, Mexico, Netherlands, Poland, Portugal, Russia, Saudi Arabia, Singapore, South Korea, Spain, Sweden, Taiwan, United Kingdom, United States
Participant flow
Recruitment details
This Phase III, multi-center, open-label study was conducted in participants with human epidermal growth factor receptor 2 (HER2)-low, hormone receptor-positive (HR+) breast cancer at 273 sites in 28 countries. Results are presented based on primary completion date (PCD) of up to 18 March 2024.
Pre-assignment details
866 participants were randomized in a 1:1 ratio to receive trastuzumab deruxtecan (T-DXd) or standard of care: Investigator's choice single agent chemotherapy (capecitabine, paclitaxel or nab-paclitaxel). As pre-specified in the protocol and statistical analysis plan (SAP), results are presented by treatment group.
Participants by arm
| Arm | Count |
|---|---|
| T-DXd Participants received T-DXd 5.4 mg/kg via IV infusion every 3 weeks until PD, unacceptable toxicity, withdrawal of consent, or another criterion for discontinuation was met. | 436 |
| Chemotherapy Participants received Investigator's choice single-agent chemotherapy (capecitabine 1000 or 1250 mg/m\^2 orally twice daily for 2 weeks followed by a 1-week rest period in 3-week cycles, paclitaxel 80 mg/m\^2 via IV infusion qw in 3-week cycles or nab-paclitaxel 100 mg/m\^2 via IV infusion qw for 3 weeks followed by 1-week rest period in 4-week cycles) until PD, unacceptable toxicity, withdrawal of consent, or another criterion for discontinuation was met. | 430 |
| Total | 866 |
Baseline characteristics
| Characteristic | T-DXd | Chemotherapy | Total |
|---|---|---|---|
| Age, Continuous | 58.2 years STANDARD_DEVIATION 11.46 | 58.2 years STANDARD_DEVIATION 10.92 | 58.2 years STANDARD_DEVIATION 11.19 |
| Race/Ethnicity, Customized American Indian or Alaska Native | 1 Participants | 0 Participants | 1 Participants |
| Race/Ethnicity, Customized Asian | 154 Participants | 151 Participants | 305 Participants |
| Race/Ethnicity, Customized Black or African American | 4 Participants | 3 Participants | 7 Participants |
| Race/Ethnicity, Customized Hispanic or Latino | 28 Participants | 32 Participants | 60 Participants |
| Race/Ethnicity, Customized Missing | 11 Participants | 11 Participants | 22 Participants |
| Race/Ethnicity, Customized Not Hispanic or Latino | 397 Participants | 387 Participants | 784 Participants |
| Race/Ethnicity, Customized Not reported | 39 Participants | 34 Participants | 73 Participants |
| Race/Ethnicity, Customized Other | 7 Participants | 12 Participants | 19 Participants |
| Race/Ethnicity, Customized White | 231 Participants | 230 Participants | 461 Participants |
| Sex: Female, Male Female | 436 Participants | 429 Participants | 865 Participants |
| Sex: Female, Male Male | 0 Participants | 1 Participants | 1 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 161 / 436 | 174 / 430 |
| other Total, other adverse events | 427 / 434 | 383 / 417 |
| serious Total, serious adverse events | 88 / 434 | 67 / 417 |
Outcome results
Primary
Progression-Free Survival (PFS) Assessed by Blinded Independent Central Review (BICR) in the Hormone Receptor-Positive (HR+), Human Epidermal Growth Factor Receptor 2 (HER2)-Low Population
PFS per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1) assessed by BICR was defined as the time from the date of randomization until the date of PD, as defined or death (by any cause in the absence of progression) regardless of whether the participant withdrew from randomized therapy or received another anticancer therapy prior to progression. PD was defined as at least a 20% increase in the sum of diameters of target lesions (TLs), taking as reference the smallest previous sum of diameters (nadir), this included the baseline sum if that was the smallest on study. In addition to the relative increase of 20%, the sum must demonstrate an absolute increase of at least 5 millimeter (mm) from nadir. Median PFS was calculated using Kaplan-Meier method and its confidence interval (CI) using Brookmeyer-Crowley method.
Time frame: Response evaluations performed at screening, every 6 weeks (q6w) ± 1 week from randomization for 48 weeks, and then every 9 weeks (q9w) ± 1 week, starting at Week 48 until PD, up to PCD of 18 March 2024 (maximum of approximately 43.85 months)
Population: The HER2-low population included the subset of participants in the ITT population with HER2 immunohistochemistry (IHC) 2+/ in situ hybridization (ISH)- and IHC 1+ as determined per the interactive response technology (IRT) data for HER2 IHC expression.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| T-DXd | Progression-Free Survival (PFS) Assessed by Blinded Independent Central Review (BICR) in the Hormone Receptor-Positive (HR+), Human Epidermal Growth Factor Receptor 2 (HER2)-Low Population | 13.2 months |
| Chemotherapy | Progression-Free Survival (PFS) Assessed by Blinded Independent Central Review (BICR) in the Hormone Receptor-Positive (HR+), Human Epidermal Growth Factor Receptor 2 (HER2)-Low Population | 8.1 months |
p-value: <0.000195% CI: [0.52, 0.75]Log Rank
Secondary
Change From Baseline in European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire-Breast Module 45 (BR45) Scale Score at Week 58
EORTC QLQ-BR45 is an updated version of the BR23. Self-administered instrument includes original 23-items yielding 5 multi-item scores (body image, sexual functioning, arm symptoms, breast symptoms, and systemic therapy side effects). Additional 22 items yield 4 additional multi-item scales (breast satisfaction, endocrine therapy symptoms, skin mucosis symptoms, and endocrine sexual symptoms). Single items assess sexual enjoyment, future perspective and being upset by hair loss. Items are scored on a 4-point verbal rating scale: 1: not at all, 2: a little, 3: quite a bit, and 4: very much; higher score: better level of functioning or greater degree of symptoms. Scores of these scales were averaged from scores of component items, transformed, and ranged from 0 to 100; higher scores for functioning scales or items indicate better functioning, whereas higher scores for symptom scales or items represent a higher level of symptoms. Baseline:last observed measurement prior to randomization.
Time frame: Baseline (Day 1) and Week 58
Population: The ITT population included all randomized participants. Only participants with data collected in specified categories are reported.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| T-DXd | Change From Baseline in European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire-Breast Module 45 (BR45) Scale Score at Week 58 | Body Image | -3.12 score on a scale | Standard Deviation 23.585 |
| T-DXd | Change From Baseline in European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire-Breast Module 45 (BR45) Scale Score at Week 58 | Sexual Functioning | -2.96 score on a scale | Standard Deviation 12.708 |
| T-DXd | Change From Baseline in European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire-Breast Module 45 (BR45) Scale Score at Week 58 | Arm Symptoms | -5.30 score on a scale | Standard Deviation 20.496 |
| T-DXd | Change From Baseline in European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire-Breast Module 45 (BR45) Scale Score at Week 58 | Breast Symptoms | -2.41 score on a scale | Standard Deviation 17.132 |
| T-DXd | Change From Baseline in European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire-Breast Module 45 (BR45) Scale Score at Week 58 | Systemic Therapy Side Effects | 5.65 score on a scale | Standard Deviation 15.536 |
| T-DXd | Change From Baseline in European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire-Breast Module 45 (BR45) Scale Score at Week 58 | Breast Satisfaction | 2.65 score on a scale | Standard Deviation 30.982 |
| T-DXd | Change From Baseline in European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire-Breast Module 45 (BR45) Scale Score at Week 58 | Endocrine Therapy Symptoms | -0.14 score on a scale | Standard Deviation 11.316 |
| T-DXd | Change From Baseline in European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire-Breast Module 45 (BR45) Scale Score at Week 58 | Skin Mucosis Symptoms | 4.67 score on a scale | Standard Deviation 14.721 |
| T-DXd | Change From Baseline in European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire-Breast Module 45 (BR45) Scale Score at Week 58 | Endocrine Sexual Symptoms | 3.66 score on a scale | Standard Deviation 20.831 |
| T-DXd | Change From Baseline in European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire-Breast Module 45 (BR45) Scale Score at Week 58 | Sexual Enjoyment | -3.03 score on a scale | Standard Deviation 17.979 |
| T-DXd | Change From Baseline in European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire-Breast Module 45 (BR45) Scale Score at Week 58 | Future Perspective | 8.72 score on a scale | Standard Deviation 32.161 |
| T-DXd | Change From Baseline in European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire-Breast Module 45 (BR45) Scale Score at Week 58 | Being Upset By Hair Loss | 2.47 score on a scale | Standard Deviation 34.5 |
| Chemotherapy | Change From Baseline in European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire-Breast Module 45 (BR45) Scale Score at Week 58 | Future Perspective | 11.25 score on a scale | Standard Deviation 29.022 |
| Chemotherapy | Change From Baseline in European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire-Breast Module 45 (BR45) Scale Score at Week 58 | Body Image | -5.42 score on a scale | Standard Deviation 22.349 |
| Chemotherapy | Change From Baseline in European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire-Breast Module 45 (BR45) Scale Score at Week 58 | Endocrine Therapy Symptoms | 0.17 score on a scale | Standard Deviation 12.458 |
| Chemotherapy | Change From Baseline in European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire-Breast Module 45 (BR45) Scale Score at Week 58 | Sexual Functioning | 1.46 score on a scale | Standard Deviation 14.081 |
| Chemotherapy | Change From Baseline in European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire-Breast Module 45 (BR45) Scale Score at Week 58 | Sexual Enjoyment | 0.00 score on a scale | Standard Deviation 20.101 |
| Chemotherapy | Change From Baseline in European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire-Breast Module 45 (BR45) Scale Score at Week 58 | Arm Symptoms | -3.06 score on a scale | Standard Deviation 18.54 |
| Chemotherapy | Change From Baseline in European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire-Breast Module 45 (BR45) Scale Score at Week 58 | Skin Mucosis Symptoms | 12.22 score on a scale | Standard Deviation 18.232 |
| Chemotherapy | Change From Baseline in European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire-Breast Module 45 (BR45) Scale Score at Week 58 | Breast Symptoms | -2.19 score on a scale | Standard Deviation 12.631 |
| Chemotherapy | Change From Baseline in European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire-Breast Module 45 (BR45) Scale Score at Week 58 | Being Upset By Hair Loss | 0.00 score on a scale | Standard Deviation 40.825 |
| Chemotherapy | Change From Baseline in European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire-Breast Module 45 (BR45) Scale Score at Week 58 | Systemic Therapy Side Effects | 3.99 score on a scale | Standard Deviation 15.536 |
| Chemotherapy | Change From Baseline in European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire-Breast Module 45 (BR45) Scale Score at Week 58 | Endocrine Sexual Symptoms | 2.00 score on a scale | Standard Deviation 15.969 |
| Chemotherapy | Change From Baseline in European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire-Breast Module 45 (BR45) Scale Score at Week 58 | Breast Satisfaction | 0.85 score on a scale | Standard Deviation 31.428 |
Secondary
Change From Baseline in European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) Scale Score at Week 91
EORTC QLQ-C30 is a 30-item self-administered questionnaire grouped into 5 multi-item functional scales(physical,role,emotional,cognitive and social),3 multiitem symptom scales(fatigue,pain and nausea/vomiting),2-item global QoL scale,5 single items assessing additional symptoms reported by cancer participants(dyspnea,loss of appetite,insomnia,constipation and diarrhea). All but 2 questions have 4-point scales:1:not at all,2:a little,3:quite a bit,4:very much.2 questions concerning global health status and QoL have 7-point scales with responses ranging from 1:very poor to 7:excellent;higher score:better level of functioning/greater degree of symptoms.For each of 15 scales,final scores were averaged from scores of component items,transformed,range: 0 to 100;higher scores:better functioning,better health related (HR)QoL,or greater level of symptoms(higher scores:opposite interpretations for functioning/QoL and symptoms/problems).Baseline:last observed measurement prior to randomization.
Time frame: Baseline (Day 1) and Week 91
Population: The ITT population included all randomized participants. Only participants with data collected in specified categories are reported.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| T-DXd | Change From Baseline in European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) Scale Score at Week 91 | Nausea/Vomiting | 9.85 score on a scale | Standard Deviation 19.128 |
| T-DXd | Change From Baseline in European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) Scale Score at Week 91 | Role Functioning | -14.77 score on a scale | Standard Deviation 21.631 |
| T-DXd | Change From Baseline in European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) Scale Score at Week 91 | Global Health Status/QoL | -7.77 score on a scale | Standard Deviation 23.529 |
| T-DXd | Change From Baseline in European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) Scale Score at Week 91 | Social Functioning | -10.98 score on a scale | Standard Deviation 23 |
| T-DXd | Change From Baseline in European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) Scale Score at Week 91 | Dyspnea | 6.06 score on a scale | Standard Deviation 23.041 |
| T-DXd | Change From Baseline in European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) Scale Score at Week 91 | Emotional Functioning | -6.06 score on a scale | Standard Deviation 25.44 |
| T-DXd | Change From Baseline in European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) Scale Score at Week 91 | Loss of Appetite | 12.88 score on a scale | Standard Deviation 30.682 |
| T-DXd | Change From Baseline in European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) Scale Score at Week 91 | Fatigue | 11.87 score on a scale | Standard Deviation 24.367 |
| T-DXd | Change From Baseline in European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) Scale Score at Week 91 | Insomnia | 6.06 score on a scale | Standard Deviation 26.19 |
| T-DXd | Change From Baseline in European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) Scale Score at Week 91 | Physical Functioning | -7.88 score on a scale | Standard Deviation 17.389 |
| T-DXd | Change From Baseline in European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) Scale Score at Week 91 | Constipation | 11.36 score on a scale | Standard Deviation 30.452 |
| T-DXd | Change From Baseline in European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) Scale Score at Week 91 | Pain | -1.89 score on a scale | Standard Deviation 21.025 |
| T-DXd | Change From Baseline in European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) Scale Score at Week 91 | Diarrhea | 6.82 score on a scale | Standard Deviation 19.792 |
| T-DXd | Change From Baseline in European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) Scale Score at Week 91 | Cognitive Functioning | -8.71 score on a scale | Standard Deviation 22.872 |
| Chemotherapy | Change From Baseline in European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) Scale Score at Week 91 | Diarrhea | 13.64 score on a scale | Standard Deviation 28.469 |
| Chemotherapy | Change From Baseline in European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) Scale Score at Week 91 | Physical Functioning | -4.85 score on a scale | Standard Deviation 13.52 |
| Chemotherapy | Change From Baseline in European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) Scale Score at Week 91 | Emotional Functioning | 1.52 score on a scale | Standard Deviation 22.218 |
| Chemotherapy | Change From Baseline in European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) Scale Score at Week 91 | Cognitive Functioning | -6.82 score on a scale | Standard Deviation 19.009 |
| Chemotherapy | Change From Baseline in European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) Scale Score at Week 91 | Social Functioning | -7.58 score on a scale | Standard Deviation 21.656 |
| Chemotherapy | Change From Baseline in European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) Scale Score at Week 91 | Fatigue | 8.59 score on a scale | Standard Deviation 18.444 |
| Chemotherapy | Change From Baseline in European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) Scale Score at Week 91 | Pain | -0.76 score on a scale | Standard Deviation 24.922 |
| Chemotherapy | Change From Baseline in European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) Scale Score at Week 91 | Nausea/Vomiting | -0.76 score on a scale | Standard Deviation 12.037 |
| Chemotherapy | Change From Baseline in European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) Scale Score at Week 91 | Global Health Status/QoL | -10.61 score on a scale | Standard Deviation 22.15 |
| Chemotherapy | Change From Baseline in European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) Scale Score at Week 91 | Dyspnea | 1.52 score on a scale | Standard Deviation 21.767 |
| Chemotherapy | Change From Baseline in European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) Scale Score at Week 91 | Loss of Appetite | 6.06 score on a scale | Standard Deviation 19.616 |
| Chemotherapy | Change From Baseline in European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) Scale Score at Week 91 | Insomnia | -15.15 score on a scale | Standard Deviation 24.618 |
| Chemotherapy | Change From Baseline in European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) Scale Score at Week 91 | Constipation | 1.52 score on a scale | Standard Deviation 12.503 |
| Chemotherapy | Change From Baseline in European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) Scale Score at Week 91 | Role Functioning | -12.12 score on a scale | Standard Deviation 26.318 |
Secondary
Duration of Response Assessed by Blinded Independent Central Review and Investigator in the Intent-to-Treat Population
DOR per RECIST v1.1 was defined as the time from the date of first documented response until date of documented progression or death in the absence of PD. PD was defined as at least a 20% increase in the sum of diameters of TLs, taking as reference the smallest previous sum of diameters (nadir), this included the baseline sum if that was the smallest on study. In addition to the relative increase of 20%, the sum must demonstrate an absolute increase of at least 5 mm from nadir. Median DOR was calculated using Kaplan-Meier method.
Time frame: Response evaluations performed at screening, q6w ± 1 week from randomization for 48 weeks, and then q9w ± 1 week, starting at Week 48 until PD, up to PCD of 18 March 2024 (maximum of approximately 43.85 months)
Population: The ITT population included all randomized participants. Only participants with response in each specified category are reported.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| T-DXd | Duration of Response Assessed by Blinded Independent Central Review and Investigator in the Intent-to-Treat Population | BICR Assessment | 13.7 months |
| T-DXd | Duration of Response Assessed by Blinded Independent Central Review and Investigator in the Intent-to-Treat Population | Investigator Assessment | 12.1 months |
| Chemotherapy | Duration of Response Assessed by Blinded Independent Central Review and Investigator in the Intent-to-Treat Population | BICR Assessment | 7.3 months |
| Chemotherapy | Duration of Response Assessed by Blinded Independent Central Review and Investigator in the Intent-to-Treat Population | Investigator Assessment | 6.9 months |
Secondary
Duration of Response (DOR) Assessed by Blinded Independent Central Review and Investigator in the Hormone Receptor-Positive, Human Epidermal Growth Factor Receptor 2-low Population
DOR per RECIST v1.1 was defined as the time from the date of first documented response until date of documented progression or death in the absence of PD. PD was defined as at least a 20% increase in the sum of diameters of TLs, taking as reference the smallest previous sum of diameters (nadir), this included the baseline sum if that was the smallest on study. In addition to the relative increase of 20%, the sum must demonstrate an absolute increase of at least 5 mm from nadir. Median DOR was calculated using Kaplan-Meier method.
Time frame: Response evaluations performed at screening, q6w ± 1 week from randomization for 48 weeks, and then q9w ± 1 week, starting at Week 48 until PD, up to PCD of 18 March 2024 (maximum of approximately 43.85 months)
Population: The HER2-low population included the subset of participants in the ITT population with HER2 IHC 2+/ISH- and IHC 1+ as determined per the IRT data for HER2 IHC expression. Only participants with response in each specified category are reported.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| T-DXd | Duration of Response (DOR) Assessed by Blinded Independent Central Review and Investigator in the Hormone Receptor-Positive, Human Epidermal Growth Factor Receptor 2-low Population | BICR Assessment | 13.6 months |
| T-DXd | Duration of Response (DOR) Assessed by Blinded Independent Central Review and Investigator in the Hormone Receptor-Positive, Human Epidermal Growth Factor Receptor 2-low Population | Investigator Assessment | 12.0 months |
| Chemotherapy | Duration of Response (DOR) Assessed by Blinded Independent Central Review and Investigator in the Hormone Receptor-Positive, Human Epidermal Growth Factor Receptor 2-low Population | BICR Assessment | 7.3 months |
| Chemotherapy | Duration of Response (DOR) Assessed by Blinded Independent Central Review and Investigator in the Hormone Receptor-Positive, Human Epidermal Growth Factor Receptor 2-low Population | Investigator Assessment | 6.9 months |
Secondary
Number of Participants With Anti-Drug Antibodies (ADAs) Against Trastuzumab Deruxtecan
Blood samples were collected at indicated timepoints to determine ADA. Treatment-induced ADA was defined as ADA positive post-baseline and not detected at baseline (negative or missing). Treatment-boosted ADA was defined as a baseline positive ADA titer that was boosted to a 4-fold or higher-level following drug administration.
Time frame: From Day 1 up to PCD of 18 March 2024 (maximum of approximately 43.85 months)
Population: The ADA population included all participants who received at least 1 dose of T-DXd and who had a non-missing ADA result at any time.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| T-DXd | Number of Participants With Anti-Drug Antibodies (ADAs) Against Trastuzumab Deruxtecan | Treatment-induced ADA | 22 Participants |
| T-DXd | Number of Participants With Anti-Drug Antibodies (ADAs) Against Trastuzumab Deruxtecan | Treatment-boosted ADA | 0 Participants |
Secondary
Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Treatment-Emergent Serious Adverse Events (TESAEs)
An adverse event (AE) was any untoward medical occurrence in a participant or clinical study participant administered a medicinal product and which did not necessarily had a causal relationship with this treatment. A serious adverse event (SAE) was an AE occurring during any study phase, that fulfilled 1 or more of following criteria: resulted in death, was immediately life-threatening, required in-participant hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability or incapacity, was congenital abnormality or birth defect, and was an important medical event that jeopardized participant or required medical treatment to prevent 1 of outcomes listed above. TEAE was any AE that occurred, having been absent before the first dose of study drug, or had worsened in severity or seriousness after initiation of the study drug until the 40-day (+7 days) safety follow-up visit.
Time frame: From first dose of study drug (Day 1) up to PCD of 18 March 2024 (maximum of approximately 43.85 months)
Population: The Safety population included all participants who received at least 1 dose of study drug.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| T-DXd | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Treatment-Emergent Serious Adverse Events (TESAEs) | TEAEs | 429 Participants |
| T-DXd | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Treatment-Emergent Serious Adverse Events (TESAEs) | TESAEs | 88 Participants |
| Chemotherapy | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Treatment-Emergent Serious Adverse Events (TESAEs) | TEAEs | 397 Participants |
| Chemotherapy | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Treatment-Emergent Serious Adverse Events (TESAEs) | TESAEs | 67 Participants |
Secondary
Objective Response Rate Assessed by Blinded Independent Central Review and Investigator in the Intent-to-Treat and Human Epidermal Growth Factor Receptor 2 Immunohistochemistry >0 <1+ Population
ORR per RECIST 1.1 assessed by BICR and Investigator was defined as the percentage of participants with at least 1 visit response of CR or PR. CR was defined as disappearance of all TLs since baseline. Any pathological lymph nodes selected as TLs must have a reduction in short axis diameter to \<10 mm. PR was defined as at least a 30% decrease in the sum of the diameters of TL, taking as reference the baseline sum of diameters.
Time frame: Response evaluations performed at screening, q6w ± 1 week from randomization for 48 weeks, and then q9w ± 1 week, starting at Week 48 until PD, up to PCD of 18 March 2024 (maximum of approximately 43.85 months)
Population: The ITT population included all randomized participants. The HER2 IHC \>0 \<1+ population included subset of participants included in ITT population with HER2 IHC \>0 \<1+ as determined by central laboratory testing and who have had at least 24 weeks of follow-up at time of interim futility PCD. Only participants with data collected in specified categories are reported.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| T-DXd | Objective Response Rate Assessed by Blinded Independent Central Review and Investigator in the Intent-to-Treat and Human Epidermal Growth Factor Receptor 2 Immunohistochemistry >0 <1+ Population | BICR Assessment: ITT Population | 61.5 percentage of participants |
| T-DXd | Objective Response Rate Assessed by Blinded Independent Central Review and Investigator in the Intent-to-Treat and Human Epidermal Growth Factor Receptor 2 Immunohistochemistry >0 <1+ Population | Investigator Assessment: ITT Population | 61.5 percentage of participants |
| T-DXd | Objective Response Rate Assessed by Blinded Independent Central Review and Investigator in the Intent-to-Treat and Human Epidermal Growth Factor Receptor 2 Immunohistochemistry >0 <1+ Population | BICR Assessment: HER2 IHC >0 <1+ Population | 67.1 percentage of participants |
| T-DXd | Objective Response Rate Assessed by Blinded Independent Central Review and Investigator in the Intent-to-Treat and Human Epidermal Growth Factor Receptor 2 Immunohistochemistry >0 <1+ Population | Investigator Assessment: HER2 IHC >0 <1+ Population | 65.8 percentage of participants |
| Chemotherapy | Objective Response Rate Assessed by Blinded Independent Central Review and Investigator in the Intent-to-Treat and Human Epidermal Growth Factor Receptor 2 Immunohistochemistry >0 <1+ Population | Investigator Assessment: HER2 IHC >0 <1+ Population | 31.6 percentage of participants |
| Chemotherapy | Objective Response Rate Assessed by Blinded Independent Central Review and Investigator in the Intent-to-Treat and Human Epidermal Growth Factor Receptor 2 Immunohistochemistry >0 <1+ Population | BICR Assessment: ITT Population | 36.7 percentage of participants |
| Chemotherapy | Objective Response Rate Assessed by Blinded Independent Central Review and Investigator in the Intent-to-Treat and Human Epidermal Growth Factor Receptor 2 Immunohistochemistry >0 <1+ Population | BICR Assessment: HER2 IHC >0 <1+ Population | 31.6 percentage of participants |
| Chemotherapy | Objective Response Rate Assessed by Blinded Independent Central Review and Investigator in the Intent-to-Treat and Human Epidermal Growth Factor Receptor 2 Immunohistochemistry >0 <1+ Population | Investigator Assessment: ITT Population | 38.8 percentage of participants |
Secondary
Objective Response Rate (ORR) Assessed by Blinded Independent Central Review and Investigator in the Hormone Receptor-Positive, Human Epidermal Growth Factor Receptor 2-low Population
ORR per RECIST 1.1 assessed by BICR and Investigator was defined as the percentage of participants with at least 1 visit response of complete response (CR) or partial response (PR). CR was defined as disappearance of all TLs since baseline. Any pathological lymph nodes selected as TLs must have a reduction in short axis diameter to \<10 mm. PR was defined as at least a 30% decrease in the sum of the diameters of TL, taking as reference the baseline sum of diameters.
Time frame: Response evaluations performed at screening, q6w ± 1 week from randomization for 48 weeks, and then q9w ± 1 week, starting at Week 48 until PD, up to PCD of 18 March 2024 (maximum of approximately 43.85 months)
Population: The HER2-low population included the subset of participants in the ITT population with HER2 IHC 2+/ISH- and IHC 1+ as determined per the IRT data for HER2 IHC expression.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| T-DXd | Objective Response Rate (ORR) Assessed by Blinded Independent Central Review and Investigator in the Hormone Receptor-Positive, Human Epidermal Growth Factor Receptor 2-low Population | BICR Assessment | 60.4 percentage of participants |
| T-DXd | Objective Response Rate (ORR) Assessed by Blinded Independent Central Review and Investigator in the Hormone Receptor-Positive, Human Epidermal Growth Factor Receptor 2-low Population | Investigator Assessment | 60.4 percentage of participants |
| Chemotherapy | Objective Response Rate (ORR) Assessed by Blinded Independent Central Review and Investigator in the Hormone Receptor-Positive, Human Epidermal Growth Factor Receptor 2-low Population | BICR Assessment | 37.9 percentage of participants |
| Chemotherapy | Objective Response Rate (ORR) Assessed by Blinded Independent Central Review and Investigator in the Hormone Receptor-Positive, Human Epidermal Growth Factor Receptor 2-low Population | Investigator Assessment | 40.4 percentage of participants |
Secondary
Overall Survival (OS) in the Hormone Receptor-Positive, Human Epidermal Growth Factor Receptor 2-low Population
OS was defined as the time from the date of randomization until death due to any cause regardless of whether the participant withdrew from randomized therapy or received another anticancer therapy. Median OS was calculated using Kaplan-Meier method and its CI using Brookmeyer-Crowley method.
Time frame: From date of randomization until death due to any cause, up to PCD of 18 March 2024 (maximum of approximately 43.85 months)
Population: The HER2-low population included the subset of participants in the ITT population with HER2 IHC 2+/ISH- and IHC 1+ as determined per the IRT data for HER2 IHC expression.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| T-DXd | Overall Survival (OS) in the Hormone Receptor-Positive, Human Epidermal Growth Factor Receptor 2-low Population | 28.9 months |
| Chemotherapy | Overall Survival (OS) in the Hormone Receptor-Positive, Human Epidermal Growth Factor Receptor 2-low Population | 27.1 months |
Secondary
Overall Survival (OS) in the Intent-to-Treat Population
OS was defined as the time from the date of randomization until death due to any cause regardless of whether the participant withdrew from randomized therapy or received another anticancer therapy. Median OS was calculated using Kaplan-Meier method and its CI using Brookmeyer-Crowley method.
Time frame: From date of randomization until death due to any cause, up to PCD of 18 March 2024 (maximum of approximately 43.85 months)
Population: The ITT population included all randomized participants.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| T-DXd | Overall Survival (OS) in the Intent-to-Treat Population | 28.9 months |
| Chemotherapy | Overall Survival (OS) in the Intent-to-Treat Population | 27.4 months |
Secondary
Progression-Free Survival Assessed by Blinded Independent Central Review in the Intent-to-Treat, Human Epidermal Growth Factor Receptor 2 Immunohistochemistry (IHC) >0 <1+ and Human Epidermal Growth Factor Receptor 2-low Population
PFS per RECIST 1.1 assessed by BICR was defined as the time from the date of randomization until the date of PD, as defined or death (by any cause in the absence of progression) regardless of whether the participant withdrew from randomized therapy or received another anticancer therapy prior to progression. PD was defined as at least a 20% increase in the sum of diameters of TLs, taking as reference the smallest previous sum of diameters (nadir), this included the baseline sum if that was the smallest on study. In addition to the relative increase of 20%, the sum must demonstrate an absolute increase of at least 5 mm from nadir. Median PFS was calculated using Kaplan-Meier method and its CI using Brookmeyer-Crowley method.
Time frame: Response evaluations performed at screening, q6w ± 1 week from randomization for 48 weeks, and then q9w ± 1 week, starting at Week 48 until PD, up to PCD of 18 March 2024 (maximum of approximately 43.85 months)
Population: ITT population: all randomized participants. HER2 IHC \>0 \<1+ population: subset of participants included in ITT population with HER2 IHC \>0 \<1+ as determined by central laboratory testing and who have had at least 24 weeks of follow-up at time of interim futility PCD. HER2-low population: subset of participants in ITT population with HER2 IHC 2+/ISH- and IHC 1+ as determined per IRT data for HER2 IHC expression. Only participants with data collected in specified categories are reported.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| T-DXd | Progression-Free Survival Assessed by Blinded Independent Central Review in the Intent-to-Treat, Human Epidermal Growth Factor Receptor 2 Immunohistochemistry (IHC) >0 <1+ and Human Epidermal Growth Factor Receptor 2-low Population | ITT Population | 13.2 months |
| T-DXd | Progression-Free Survival Assessed by Blinded Independent Central Review in the Intent-to-Treat, Human Epidermal Growth Factor Receptor 2 Immunohistochemistry (IHC) >0 <1+ and Human Epidermal Growth Factor Receptor 2-low Population | HER2 IHC >0 <1+ Population | 13.2 months |
| T-DXd | Progression-Free Survival Assessed by Blinded Independent Central Review in the Intent-to-Treat, Human Epidermal Growth Factor Receptor 2 Immunohistochemistry (IHC) >0 <1+ and Human Epidermal Growth Factor Receptor 2-low Population | HER2-low Population | 12.8 months |
| Chemotherapy | Progression-Free Survival Assessed by Blinded Independent Central Review in the Intent-to-Treat, Human Epidermal Growth Factor Receptor 2 Immunohistochemistry (IHC) >0 <1+ and Human Epidermal Growth Factor Receptor 2-low Population | ITT Population | 8.1 months |
| Chemotherapy | Progression-Free Survival Assessed by Blinded Independent Central Review in the Intent-to-Treat, Human Epidermal Growth Factor Receptor 2 Immunohistochemistry (IHC) >0 <1+ and Human Epidermal Growth Factor Receptor 2-low Population | HER2 IHC >0 <1+ Population | 8.3 months |
| Chemotherapy | Progression-Free Survival Assessed by Blinded Independent Central Review in the Intent-to-Treat, Human Epidermal Growth Factor Receptor 2 Immunohistochemistry (IHC) >0 <1+ and Human Epidermal Growth Factor Receptor 2-low Population | HER2-low Population | 7.0 months |
Secondary
Progression-Free Survival Assessed by Investigator in the Hormone Receptor-Positive, Human Epidermal Growth Factor Receptor 2-low Population
PFS per RECIST 1.1 assessed by Investigator was defined as the time from the date of randomization until the date of PD, as defined or death (by any cause in the absence of progression) regardless of whether the participant withdrew from randomized therapy or received another anticancer therapy prior to progression. PD was defined as at least a 20% increase in the sum of diameters of TLs, taking as reference the smallest previous sum of diameters (nadir), this included the baseline sum if that was the smallest on study. In addition to the relative increase of 20%, the sum must demonstrate an absolute increase of at least 5 mm from nadir. Median PFS was calculated using Kaplan-Meier method and its CI using Brookmeyer-Crowley method.
Time frame: Response evaluations performed at screening, q6w ± 1 week from randomization for 48 weeks, and then q9w ± 1 week, starting at Week 48 until PD, up to PCD of 18 March 2024 (maximum of approximately 43.85 months)
Population: The HER2-low population included the subset of participants in the ITT population with HER2 IHC 2+/ISH- and IHC 1+ as determined per the IRT data for HER2 IHC expression.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| T-DXd | Progression-Free Survival Assessed by Investigator in the Hormone Receptor-Positive, Human Epidermal Growth Factor Receptor 2-low Population | 12.8 months |
| Chemotherapy | Progression-Free Survival Assessed by Investigator in the Hormone Receptor-Positive, Human Epidermal Growth Factor Receptor 2-low Population | 7.0 months |
Secondary
Serum Concentration of Trastuzumab Deruxtecan (T-DXd), Total Anti-Human Epidermal Growth Factor Receptor 2 Antibody and MAAA-1181a
Blood samples were collected at indicated time points to determine the concentration of T-DXd, total anti-HER2 antibody and MAAA-1181a in serum.
Time frame: Pre-dose on Day 1 of Cycles 1, 2, 4, 6 and 8; 15 minutes post-dose on Day 1 of Cycles 1, 2 and 4; and 5 hours post-dose on Day 1 of Cycle 1 (each cycle is 21 days)
Population: The Pharmacokinetic population included all participants who received at least 1 dose of T-DXd per the protocol for whom any post-dose data were available. Only participants with data collected in specified timepoints are reported.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| T-DXd | Serum Concentration of Trastuzumab Deruxtecan (T-DXd), Total Anti-Human Epidermal Growth Factor Receptor 2 Antibody and MAAA-1181a | MAAA-1181a: Day 1: pre-dose, Cycle 1 | NA micrograms per milliliter (mcg/mL) | — |
| T-DXd | Serum Concentration of Trastuzumab Deruxtecan (T-DXd), Total Anti-Human Epidermal Growth Factor Receptor 2 Antibody and MAAA-1181a | MAAA-1181a: Day 1: pre-dose, Cycle 2 | 0.261850 micrograms per milliliter (mcg/mL) | Standard Deviation 0.2096642 |
| T-DXd | Serum Concentration of Trastuzumab Deruxtecan (T-DXd), Total Anti-Human Epidermal Growth Factor Receptor 2 Antibody and MAAA-1181a | T-DXd: Day 1: pre-dose, Cycle 1 | NA micrograms per milliliter (mcg/mL) | — |
| T-DXd | Serum Concentration of Trastuzumab Deruxtecan (T-DXd), Total Anti-Human Epidermal Growth Factor Receptor 2 Antibody and MAAA-1181a | T-DXd: Day 1: pre-dose, Cycle 2 | 4.35225 micrograms per milliliter (mcg/mL) | Standard Deviation 8.958729 |
| T-DXd | Serum Concentration of Trastuzumab Deruxtecan (T-DXd), Total Anti-Human Epidermal Growth Factor Receptor 2 Antibody and MAAA-1181a | T-DXd: Day 1: pre-dose, Cycle 4 | 8.21037 micrograms per milliliter (mcg/mL) | Standard Deviation 9.464435 |
| T-DXd | Serum Concentration of Trastuzumab Deruxtecan (T-DXd), Total Anti-Human Epidermal Growth Factor Receptor 2 Antibody and MAAA-1181a | T-DXd: Day 1: pre-dose, Cycle 6 | 8.65950 micrograms per milliliter (mcg/mL) | Standard Deviation 4.753592 |
| T-DXd | Serum Concentration of Trastuzumab Deruxtecan (T-DXd), Total Anti-Human Epidermal Growth Factor Receptor 2 Antibody and MAAA-1181a | T-DXd: Day 1: pre-dose, Cycle 8 | 11.31496 micrograms per milliliter (mcg/mL) | Standard Deviation 22.894112 |
| T-DXd | Serum Concentration of Trastuzumab Deruxtecan (T-DXd), Total Anti-Human Epidermal Growth Factor Receptor 2 Antibody and MAAA-1181a | T-DXd: Day 1: 15 minutes post-dose, Cycle 1 | 135.90160 micrograms per milliliter (mcg/mL) | Standard Deviation 102.989325 |
| T-DXd | Serum Concentration of Trastuzumab Deruxtecan (T-DXd), Total Anti-Human Epidermal Growth Factor Receptor 2 Antibody and MAAA-1181a | T-DXd: Day 1: 15 minutes post-dose, Cycle 2 | 136.74872 micrograms per milliliter (mcg/mL) | Standard Deviation 108.860006 |
| T-DXd | Serum Concentration of Trastuzumab Deruxtecan (T-DXd), Total Anti-Human Epidermal Growth Factor Receptor 2 Antibody and MAAA-1181a | T-DXd: Day 1: 15 minutes post-dose, Cycle 4 | 124.60481 micrograms per milliliter (mcg/mL) | Standard Deviation 39.812165 |
| T-DXd | Serum Concentration of Trastuzumab Deruxtecan (T-DXd), Total Anti-Human Epidermal Growth Factor Receptor 2 Antibody and MAAA-1181a | T-DXd: Day 1: 5 hours post-dose, Cycle 1 | 123.82288 micrograms per milliliter (mcg/mL) | Standard Deviation 30.513998 |
| T-DXd | Serum Concentration of Trastuzumab Deruxtecan (T-DXd), Total Anti-Human Epidermal Growth Factor Receptor 2 Antibody and MAAA-1181a | Total anti-HER2 antibody: Day 1: pre-dose, Cycle 1 | NA micrograms per milliliter (mcg/mL) | — |
| T-DXd | Serum Concentration of Trastuzumab Deruxtecan (T-DXd), Total Anti-Human Epidermal Growth Factor Receptor 2 Antibody and MAAA-1181a | Total anti-HER2 antibody: Day 1: pre-dose, Cycle 2 | 5.75841 micrograms per milliliter (mcg/mL) | Standard Deviation 11.351915 |
| T-DXd | Serum Concentration of Trastuzumab Deruxtecan (T-DXd), Total Anti-Human Epidermal Growth Factor Receptor 2 Antibody and MAAA-1181a | Total anti-HER2 antibody: Day 1: pre-dose, Cycle 4 | 12.00513 micrograms per milliliter (mcg/mL) | Standard Deviation 11.087226 |
| T-DXd | Serum Concentration of Trastuzumab Deruxtecan (T-DXd), Total Anti-Human Epidermal Growth Factor Receptor 2 Antibody and MAAA-1181a | Total anti-HER2 antibody: Day 1: pre-dose, Cycle 6 | 13.97891 micrograms per milliliter (mcg/mL) | Standard Deviation 8.72079 |
| T-DXd | Serum Concentration of Trastuzumab Deruxtecan (T-DXd), Total Anti-Human Epidermal Growth Factor Receptor 2 Antibody and MAAA-1181a | Total anti-HER2 antibody: Day 1: pre-dose, Cycle 8 | 17.47641 micrograms per milliliter (mcg/mL) | Standard Deviation 27.144299 |
| T-DXd | Serum Concentration of Trastuzumab Deruxtecan (T-DXd), Total Anti-Human Epidermal Growth Factor Receptor 2 Antibody and MAAA-1181a | Total anti-HER2 antibody: Day 1: 15 minutes post-dose, Cycle 1 | 141.27586 micrograms per milliliter (mcg/mL) | Standard Deviation 114.137606 |
| T-DXd | Serum Concentration of Trastuzumab Deruxtecan (T-DXd), Total Anti-Human Epidermal Growth Factor Receptor 2 Antibody and MAAA-1181a | Total anti-HER2 antibody: Day 1: 15 minutes post-dose, Cycle 2 | 146.17993 micrograms per milliliter (mcg/mL) | Standard Deviation 134.780719 |
| T-DXd | Serum Concentration of Trastuzumab Deruxtecan (T-DXd), Total Anti-Human Epidermal Growth Factor Receptor 2 Antibody and MAAA-1181a | Total anti-HER2 antibody: Day 1: 15 minutes post-dose, Cycle 4 | 131.06830 micrograms per milliliter (mcg/mL) | Standard Deviation 44.22838 |
| T-DXd | Serum Concentration of Trastuzumab Deruxtecan (T-DXd), Total Anti-Human Epidermal Growth Factor Receptor 2 Antibody and MAAA-1181a | Total anti-HER2 antibody: Day 1: 5 hours post-dose, Cycle 1 | 119.64619 micrograms per milliliter (mcg/mL) | Standard Deviation 26.591288 |
| T-DXd | Serum Concentration of Trastuzumab Deruxtecan (T-DXd), Total Anti-Human Epidermal Growth Factor Receptor 2 Antibody and MAAA-1181a | MAAA-1181a: Day 1: pre-dose, Cycle 4 | 0.401004 micrograms per milliliter (mcg/mL) | Standard Deviation 0.2825761 |
| T-DXd | Serum Concentration of Trastuzumab Deruxtecan (T-DXd), Total Anti-Human Epidermal Growth Factor Receptor 2 Antibody and MAAA-1181a | MAAA-1181a: Day 1: pre-dose, Cycle 6 | 0.446237 micrograms per milliliter (mcg/mL) | Standard Deviation 0.2957478 |
| T-DXd | Serum Concentration of Trastuzumab Deruxtecan (T-DXd), Total Anti-Human Epidermal Growth Factor Receptor 2 Antibody and MAAA-1181a | MAAA-1181a: Day 1: pre-dose, Cycle 8 | 0.432894 micrograms per milliliter (mcg/mL) | Standard Deviation 0.2819292 |
| T-DXd | Serum Concentration of Trastuzumab Deruxtecan (T-DXd), Total Anti-Human Epidermal Growth Factor Receptor 2 Antibody and MAAA-1181a | MAAA-1181a: Day 1: 15 minutes post-dose, Cycle 1 | 6.014366 micrograms per milliliter (mcg/mL) | Standard Deviation 3.1859583 |
| T-DXd | Serum Concentration of Trastuzumab Deruxtecan (T-DXd), Total Anti-Human Epidermal Growth Factor Receptor 2 Antibody and MAAA-1181a | MAAA-1181a: Day 1: 15 minutes post-dose, Cycle 2 | 2.985606 micrograms per milliliter (mcg/mL) | Standard Deviation 1.927612 |
| T-DXd | Serum Concentration of Trastuzumab Deruxtecan (T-DXd), Total Anti-Human Epidermal Growth Factor Receptor 2 Antibody and MAAA-1181a | MAAA-1181a: Day 1: 15 minutes post-dose, Cycle 4 | 2.411409 micrograms per milliliter (mcg/mL) | Standard Deviation 1.5862547 |
| T-DXd | Serum Concentration of Trastuzumab Deruxtecan (T-DXd), Total Anti-Human Epidermal Growth Factor Receptor 2 Antibody and MAAA-1181a | MAAA-1181a: Day 1: 5 hours post-dose, Cycle 1 | 13.917874 micrograms per milliliter (mcg/mL) | Standard Deviation 6.5178612 |
Secondary
Time From Randomization to Second Progression or Death (PFS2) in the Hormone Receptor-Positive, Human Epidermal Growth Factor Receptor 2-low and Intent-to-Treat Population
PFS2 was defined as time from randomization to second progression (the earliest of the progression event subsequent to first subsequent therapy) or death; second progression was defined according to local standard clinical practice and might involve any of the following: objective radiological imaging, symptomatic progression, or death. Median PFS2 was calculated using Kaplan-Meier method and its CI using Brookmeyer-Crowley method.
Time frame: Response evaluations performed at screening, q6w ± 1 week from randomization for 48 weeks, and then q9w ± 1 week, starting at Week 48 until PD, up to PCD of 18 March 2024 (maximum of approximately 43.85 months)
Population: The HER2-low population included subset of participants in ITT population with HER2 IHC 2+/ISH- and IHC 1+ as determined per IRT data for HER2 IHC expression. The ITT population included all randomized participants. Only participants with data collected in specified categories are reported.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| T-DXd | Time From Randomization to Second Progression or Death (PFS2) in the Hormone Receptor-Positive, Human Epidermal Growth Factor Receptor 2-low and Intent-to-Treat Population | HER2-low Population | 20.0 months |
| T-DXd | Time From Randomization to Second Progression or Death (PFS2) in the Hormone Receptor-Positive, Human Epidermal Growth Factor Receptor 2-low and Intent-to-Treat Population | ITT Population | 20.3 months |
| Chemotherapy | Time From Randomization to Second Progression or Death (PFS2) in the Hormone Receptor-Positive, Human Epidermal Growth Factor Receptor 2-low and Intent-to-Treat Population | HER2-low Population | 14.5 months |
| Chemotherapy | Time From Randomization to Second Progression or Death (PFS2) in the Hormone Receptor-Positive, Human Epidermal Growth Factor Receptor 2-low and Intent-to-Treat Population | ITT Population | 14.7 months |
Secondary
Time to Deterioration in European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 Scale Score
Time to deterioration was defined as the time from randomization until the date of the first clinically meaningful deterioration that was confirmed at next available assessment, at least 14 days apart, regardless of whether the participant withdrew from study treatment or receives another anti-cancer therapy prior to deterioration.
Time frame: From randomization until date of first symptom deterioration that is confirmed, up to PCD of 18 March 2024 (maximum of approximately 43.85 months)
Population: The ITT population included all randomized participants.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| T-DXd | Time to Deterioration in European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 Scale Score | Constipation | 9.2 months |
| T-DXd | Time to Deterioration in European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 Scale Score | Emotional Functioning | 28.2 months |
| T-DXd | Time to Deterioration in European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 Scale Score | Dyspnea | 20.0 months |
| T-DXd | Time to Deterioration in European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 Scale Score | Cognitive Functioning | 11.8 months |
| T-DXd | Time to Deterioration in European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 Scale Score | Social Functioning | 11.7 months |
| T-DXd | Time to Deterioration in European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 Scale Score | Diarrhea | 29.0 months |
| T-DXd | Time to Deterioration in European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 Scale Score | Fatigue | 4.3 months |
| T-DXd | Time to Deterioration in European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 Scale Score | Insomnia | NA months |
| T-DXd | Time to Deterioration in European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 Scale Score | Pain | 22.0 months |
| T-DXd | Time to Deterioration in European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 Scale Score | Physical Functioning | 18.0 months |
| T-DXd | Time to Deterioration in European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 Scale Score | Nausea/Vomiting | 3.5 months |
| T-DXd | Time to Deterioration in European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 Scale Score | Loss of Appetite | 8.3 months |
| T-DXd | Time to Deterioration in European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 Scale Score | Global Health Status/QoL | 11.3 months |
| T-DXd | Time to Deterioration in European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 Scale Score | Role Functioning | 10.3 months |
| Chemotherapy | Time to Deterioration in European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 Scale Score | Global Health Status/QoL | 10.5 months |
| Chemotherapy | Time to Deterioration in European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 Scale Score | Dyspnea | 20.8 months |
| Chemotherapy | Time to Deterioration in European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 Scale Score | Loss of Appetite | 13.8 months |
| Chemotherapy | Time to Deterioration in European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 Scale Score | Insomnia | 15.2 months |
| Chemotherapy | Time to Deterioration in European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 Scale Score | Constipation | 22.0 months |
| Chemotherapy | Time to Deterioration in European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 Scale Score | Diarrhea | 16.5 months |
| Chemotherapy | Time to Deterioration in European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 Scale Score | Physical Functioning | 9.9 months |
| Chemotherapy | Time to Deterioration in European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 Scale Score | Role Functioning | 5.5 months |
| Chemotherapy | Time to Deterioration in European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 Scale Score | Emotional Functioning | 17.3 months |
| Chemotherapy | Time to Deterioration in European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 Scale Score | Social Functioning | 7.7 months |
| Chemotherapy | Time to Deterioration in European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 Scale Score | Fatigue | 2.9 months |
| Chemotherapy | Time to Deterioration in European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 Scale Score | Pain | 6.3 months |
| Chemotherapy | Time to Deterioration in European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 Scale Score | Nausea/Vomiting | 13.8 months |
| Chemotherapy | Time to Deterioration in European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 Scale Score | Cognitive Functioning | 9.9 months |
Secondary
Time to First Subsequent Treatment or Death (TFST) in the Hormone Receptor-Positive, Human Epidermal Growth Factor Receptor 2-low and Intent-to-Treat Population
TFST was defined as time from randomization to the start date of the first subsequent anti-cancer therapy after discontinuation of randomized treatment or death due to any cause.
Time frame: From Day 1 up to 64 months
Secondary
Time to Second Subsequent Treatment or Death (TSST) in the Hormone Receptor-Positive, Human Epidermal Growth Factor Receptor 2-low and Intent-to-Treat Population
TSST was defined as time from randomization to the start date of the second subsequent anti-cancer therapy after discontinuation of randomized treatment or death due to any cause.
Time frame: From Day 1 up to 64 months