This page provides an independent statistical analysis and educational interpretation of publicly reported results. ClinicalTrials.gov provides the official trial registry record. Numerical trial results on this page are restricted to the results posted in the ClinicalTrials.gov record; calculations added by Clinical Biostats are labelled as such.
1. Trial at a Glance
This page covers the registry results for DS-8201a Versus T-DM1 for Human Epidermal Growth Factor Receptor 2 (HER2)-Positive, Unresectable and/or Metastatic Breast Cancer Previously Treated With Trastuzumab and Taxane [DESTINY-Breast03] (NCT03529110), a randomized phase 3 study. The primary outcome is Progression-Free Survival (PFS) Based on Blinded Independent Central Review (BICR) in Participants With HER2-Positive, Unresectable and/or Metastatic Breast Cancer Previously Treated With Trastuzumab and Taxane.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT03529110 |
| Phase | Phase 3 |
| Condition | Breast Cancer |
| Allocation | Randomized |
| Design model | Parallel |
| Masking | None (open label) |
| Enrollment | 524 |
| Arms in the primary outcome | 2 |
| Lead sponsor | Daiichi Sankyo |
| Results posted | Yes |
2. Clinical Question
Population
Participants had HER2-positive, unresectable and/or metastatic breast cancer and had previously been treated with trastuzumab and taxane. The primary outcome was assessed in the Full Analysis Set at the data cut-off date of 21 May 2021. The registry record reports enrollment of 524 participants.
Intervention
One group received trastuzumab deruxtecan (T-DXd) as an intravenous solution at 5.4 mg/kg every 3 weeks. The registry record describes 261 participants in this arm.
Comparator
The active-control group received ado-trastuzumab emtansine (T-DM1) in accordance with the approved label. The registry record describes 263 participants in this arm.
Primary question
The primary question was how progression-free survival, assessed by blinded independent central review, compared between the groups. Progression-free survival was measured from enrollment until the first objective documentation of disease progression or death from any cause, whichever occurred first.
3. Trial Design
This was a phase 3, multicenter, randomized, open-label, active-controlled, parallel-group study sponsored by Daiichi Sankyo. Its stated purpose was to compare the anti-tumor activity, safety and efficacy of trastuzumab deruxtecan with T-DM1 in participants with HER2-positive, unresectable and/or metastatic breast cancer previously treated with trastuzumab and taxane. The registry record lists the study as completed.
Participants were assigned to one of two treatment groups. The trastuzumab deruxtecan group received 5.4 mg/kg intravenously every 3 weeks. The T-DM1 group received treatment in accordance with the approved label. The record lists 261 participants in the trastuzumab deruxtecan arm and 263 in the T-DM1 arm, with overall enrollment of 524.
The study was open-label, so treatment assignment was not masked from participants or study personnel as described in the registry. The primary endpoint, however, was assessed by blinded independent central review (BICR). That distinction matters: the trial’s treatment assignment was open, while the stated primary endpoint relied on an independent review process described as blinded. The registry record does not report further details about how that review was conducted.
The primary outcome was median progression-free survival (PFS) by BICR, with a timeframe of up to 33 months at data cut-off. The registry also lists four secondary outcomes: overall survival, objective response rate, duration of response, and PFS based on investigator assessment. The record does not include posted analysis entries for these outcomes.
4. Participant Flow and Accounting
The registry reports how participants moved through each stage of the study. All counts below are exactly as posted; missing counts are not inferred from other stages.
Overall Study
| Stage | Trastuzumab Deruxtecan (T-DXd) | Ado-trastuzumab Emtansine (T-DM1) |
|---|---|---|
| STARTED | 261 | 263 |
| COMPLETED | 136 | 49 |
| NOT COMPLETED | 125 | 214 |
Reasons for not completing this period:
| Reason | Trastuzumab Deruxtecan (T-DXd) | Ado-trastuzumab Emtansine (T-DM1) |
|---|---|---|
| Progressive Disease | 66 | 158 |
| Clinical Progression | 4 | 12 |
| Adverse Event | 35 | 17 |
| Withdrawal by Subject (from treatment only) | 13 | 11 |
| Lack of Efficacy | 3 | 3 |
| Physician Decision | 2 | 8 |
| Miscellaneous | 2 | 5 |
Analysis population for the primary outcome, as defined in the registry: Progression-free survival (PFS) was assessed in the Full Analysis Set at data cut-off date of 21 May 2021.
5. Baseline Characteristics
The table reproduces the baseline characteristics posted in the registry, which describe the participants analysed at baseline and help show whether the randomized groups were comparable.
Population: Baseline characteristics were assessed using the Full Analysis Set.
| Characteristic | Unit | Trastuzumab Deruxtecan (T-DXd) | Ado-trastuzumab Emtansine (T-DM1) | Total |
|---|---|---|---|---|
| Participants analysed | 261 | 263 | 524 | |
| Age, Categorical: <=18 years | Participants | 0 | 0 | 0 |
| Age, Categorical: Between 18 and 65 years | Participants | 212 | 206 | 418 |
| Age, Categorical: >=65 years | Participants | 49 | 57 | 106 |
| Age, Continuous | years | 54.5 (SD 11.11) | 54.2 (SD 11.84) | 54.4 (SD 11.47) |
| Sex: Female, Male: Female | Participants | 260 | 262 | 522 |
| Sex: Female, Male: Male | Participants | 1 | 1 | 2 |
| Race (NIH/OMB): American Indian or Alaska Native | Participants | 0 | 0 | 0 |
| Race (NIH/OMB): Asian | Participants | 152 | 162 | 314 |
| Race (NIH/OMB): Native Hawaiian or Other Pacific Islander | Participants | 0 | 0 | 0 |
| Race (NIH/OMB): Black or African American | Participants | 10 | 9 | 19 |
| Race (NIH/OMB): White | Participants | 71 | 72 | 143 |
| Race (NIH/OMB): More than one race | Participants | 2 | 0 | 2 |
| Race (NIH/OMB): Unknown or Not Reported | Participants | 26 | 20 | 46 |
6. Primary Endpoint
The registry lists the primary outcome as Progression-Free Survival (PFS) Based on Blinded Independent Central Review (BICR) in Participants With HER2-Positive, Unresectable and/or Metastatic Breast Cancer Previously Treated With Trastuzumab and Taxane, measured over Up to 33 months (data cut-off).
| Element | Registry entry |
|---|---|
| Result type | Median |
| Measure of spread | 95% Confidence Interval |
| Unit | months |
| Endpoint classification | Time-to-Event Analysis |
Progression-free survival measures the time participants remain alive without documented disease progression. In this trial, the interval began on the date of enrollment and ended at the earlier of the first objective documentation of disease progression under RECIST v1.1 or death due to any cause. The registry definition describes progressive disease as at least a 20% increase in the sum of the diameters of target lesions.
The primary summary was the median PFS in each group. A median is the time by which half of the analyzed group has experienced the defined event, subject to the study’s time-to-event analysis. It is a way to describe the distribution of time to progression or death; it does not describe every participant’s course or show the size of a treatment effect on its own.
PFS is used as a time-to-event endpoint because it incorporates both whether an event occurred and when it occurred. The endpoint also counts death from any cause, not only death attributed to cancer. BICR was the specified assessment source for the primary outcome, while investigator-assessed PFS was listed separately as a secondary outcome. The registry record reports that PFS was assessed in the Full Analysis Set at the 21 May 2021 data cut-off.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The posted median PFS for the T-DM1 group is 6.8 months, with a 95% confidence interval from 5.6 to 8.2 months. For the trastuzumab deruxtecan group, the registry record does not report a median value; it lists a lower confidence limit of 18.5 months and no upper confidence limit. The missing median and incomplete interval mean that the two groups’ medians cannot be compared as a complete pair using the posted figures.
A confidence interval conveys uncertainty around an estimated quantity under the statistical method used. It is not a range containing every participant’s PFS time, and it does not by itself establish whether a difference between groups is statistically persuasive. The posted T-DM1 interval describes uncertainty around that group’s median. The available trastuzumab deruxtecan entry does not provide a complete median estimate and interval for a parallel reading.
The registry record contains no posted analysis entries and no hazard ratio or p-value for the primary endpoint. A hazard ratio can summarize the relative rate of events over follow-up under a time-to-event analysis, while the medians describe a point in each group’s event-time distribution. The posted median figures alone cannot substitute for a sponsor-reported hazard ratio, establish the relative event rate, or determine statistical significance. No unadjusted re-calculation is reported for this comparison.
The time frame is listed as up to 33 months at data cut-off, and the primary analysis population is identified as the Full Analysis Set. The actual follow-up distribution, numbers at risk over time, event counts for PFS, censoring details and handling of missing outcome data are not reported in the registry record. Those details would help readers understand how much information contributed to the time-to-event estimates and how much uncertainty remains.
The results should therefore be read narrowly: the record posts a median and 95% confidence interval for T-DM1 and a lower confidence limit, but not a median or upper limit, for trastuzumab deruxtecan. It does not post the comparative analysis needed to quantify the difference between groups. These limitations do not alter the reported figures; they define what can and cannot be concluded from them.
9. Statistical Methods Explained
The primary endpoint is a time-to-event outcome. General statistical explanation: time-to-event methods account for both the time until an event and the fact that some participants may not have had an observed event by the end of available follow-up. Participants without an observed event can contribute information up to the point their follow-up ends, under the analysis method’s assumptions. The registry record does not describe the censoring rules or the specific statistical model used for the primary comparison.
What does the median describe?
General statistical explanation: the median is the time at which the estimated event-free proportion reaches the halfway point. For PFS, the event is the first documented progression or death, whichever occurs first. This summary is different from an average: it is based on the midpoint of the event-time distribution rather than the arithmetic mean of individual times. It also does not say that all participants experienced the event at the median time.
The record reports a T-DM1 median of 6.8 months, with a 95% confidence interval of 5.6 to 8.2 months. For trastuzumab deruxtecan, the median is not reported in the registry record; the lower confidence limit is 18.5 months and the upper confidence limit is not reported. Without both medians and a comparative analysis, readers cannot use these entries alone to quantify the between-group effect.
How should a confidence interval be read?
General statistical explanation: a confidence interval expresses uncertainty about an estimate using a specified statistical procedure. It is not an interval for individual participant outcomes. The width and limits depend on the data and method, and an interval for one group does not directly test the difference between groups. Comparing whether two separate intervals overlap is not a substitute for a formal comparison of the groups.
The registry identifies the dispersion measure as a 95% confidence interval. The T-DM1 interval is complete in the posted result, but the trastuzumab deruxtecan entry has no reported median or upper limit. Consequently, the interval information does not permit a complete side-by-side comparison of median estimates.
What does blinded independent review add?
The primary PFS assessment was based on blinded independent central review. General statistical explanation: independent review can provide an assessment separate from the treating investigator’s assessment, and blinding can reduce the possibility that knowledge of treatment assignment influences outcome classification. It does not remove every source of uncertainty, and it does not replace the need for a clearly reported comparative statistical analysis. The trial itself was open-label, while the primary endpoint was specified as BICR-assessed.
The registry lists investigator-assessed PFS as a secondary outcome, allowing a different assessment source to be distinguished from the primary one. The record does not post analysis results for that secondary outcome or detail how disagreements between assessments were handled.
Why is the hazard ratio not interchangeable with a median?
General statistical explanation: a hazard ratio is a relative summary of event rates over follow-up, whereas a median is a time point in an estimated event-time distribution. They answer related but different questions. A hazard ratio requires an analysis of event timing across follow-up; it cannot be derived from the two posted median entries alone. The registry record contains no posted hazard ratio for this primary outcome, and no p-value or other comparative analysis is listed.
Time-to-event analyses can also be affected by the amount and pattern of follow-up, the number of events, and assumptions about censoring. General statistical explanation: when the event rate changes over time, a single hazard ratio may not capture the entire pattern equally well at every point in follow-up. The registry record does not report whether this issue was assessed or what model was used.
What can sample-size calculations establish?
General statistical explanation: a sample-size calculation is a planning exercise based on assumptions about the effect to detect, variability or event rates, significance level and allocation. It does not show that a completed trial had a particular probability of detecting an effect after the results are known; that would be an observed-power interpretation and should not be inferred. The stated planning illustration assumptions use a two-sided significance level of 0.05, equal allocation and a normal approximation, with the target effect expressed as a fraction of the observed effect. For time-to-event outcomes, the stated illustration is based on a total event count.
The registry record does not report the trial’s own sample-size justification or the assumptions used to plan enrollment. The posted medians are not enough to recreate a comparative time-to-event calculation, and no sponsor-reported hazard ratio is posted. No planning illustration should therefore be treated as an observed trial result.
10. Multiplicity, Missing Data and Analysis Populations
The registry record lists five outcome measures in total: the primary PFS outcome and four secondary outcomes. The secondary outcomes are overall survival, objective response rate, duration of response and investigator-assessed PFS. It contains no posted analysis entries. Results for those secondary outcomes are therefore not reported in the registry record represented by these results.
When a trial evaluates multiple outcomes or makes multiple statistical comparisons, the chance of at least one apparently positive result can increase if each is interpreted independently. General statistical explanation: a multiplicity plan specifies how the analyses are prioritized or how error rates are controlled. The registry record does not report a multiplicity strategy, a testing hierarchy, or which outcomes were intended to support formal claims.
Details of missing-data handling are not reported in the registry record. For a time-to-event endpoint, the treatment of participants who leave follow-up or have no documented event is important because their information is generally censored at a specified point under the analysis method. The record does not describe censoring rules, reasons for censoring, or sensitivity analyses for missing or incomplete follow-up.
The primary outcome population is identified as the Full Analysis Set, assessed at the 21 May 2021 data cut-off. The registry does not define the Full Analysis Set further in the posted description. A detailed population definition, analysis plan, interim analysis information and protocol-specific sample-size justification are not reported in the registry record. The record’s lack of posted analysis entries also means that comparative estimates and uncertainty for the listed secondary outcomes cannot be assessed from these results.
11. Safety Results
The registry reports serious adverse events as affected participants divided by participants at risk.
| Arm | Participants with serious adverse events | Participants at risk | Percentage |
|---|---|---|---|
| Trastuzumab Deruxtecan (T-DXd) | 49 | 257 | 19.1% |
| Ado-trastuzumab Emtansine (T-DM1) | 47 | 261 | 18.0% |
Deaths
| Arm | Deaths (participants affected of at risk) |
|---|---|
| Trastuzumab Deruxtecan (T-DXd) | 33 of 257 |
| Ado-trastuzumab Emtansine (T-DM1) | 53 of 261 |
Other (non-serious) adverse events
Participants with at least one non-serious event at or above the registry's 5% reporting threshold.
| Arm | Participants affected of at risk |
|---|---|
| Trastuzumab Deruxtecan (T-DXd) | 256 of 257 |
| Ado-trastuzumab Emtansine (T-DM1) | 249 of 261 |
Most frequent serious adverse event terms
| Event term | Organ system | Trastuzumab Deruxtecan (T-DXd) | Ado-trastuzumab Emtansine (T-DM1) |
|---|---|---|---|
| Pneumonia | Infections and infestations | 4 of 257 | 5 of 261 |
| Vomiting | Gastrointestinal disorders | 5 of 257 | 2 of 261 |
| Interstitial lung disease | Respiratory, thoracic and mediastinal disorders | 5 of 257 | 0 of 261 |
| Anaemia | Blood and lymphatic system disorders | 2 of 257 | 3 of 261 |
| Pyrexia | General disorders | 4 of 257 | 0 of 261 |
| Disease progression | General disorders | 3 of 257 | 1 of 261 |
| Urinary tract infection | Infections and infestations | 3 of 257 | 1 of 261 |
| COVID-19 | Infections and infestations | 1 of 257 | 2 of 261 |
| Platelet count decreased | Investigations | 0 of 257 | 3 of 261 |
| Cellulitis | Infections and infestations | 2 of 257 | 0 of 261 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Trastuzumab Deruxtecan (T-DXd) | Ado-trastuzumab Emtansine (T-DM1) |
|---|---|---|---|
| Nausea | Gastrointestinal disorders | 195 of 257 | 79 of 261 |
| Aspartate aminotransferase increased | Investigations | 66 of 257 | 105 of 261 |
| Platelet count decreased | Investigations | 54 of 257 | 112 of 261 |
| Vomiting | Gastrointestinal disorders | 126 of 257 | 26 of 261 |
| Constipation | Gastrointestinal disorders | 88 of 257 | 51 of 261 |
| Alanine aminotransferase increased | Investigations | 56 of 257 | 77 of 261 |
| Anaemia | Blood and lymphatic system disorders | 83 of 257 | 43 of 261 |
| Fatigue | General disorders | 74 of 257 | 52 of 261 |
| Decreased appetite | Metabolism and nutrition disorders | 75 of 257 | 44 of 261 |
| Alopecia | Skin and subcutaneous tissue disorders | 95 of 257 | 8 of 261 |
Serious events with the highest arm-level rate: vomiting (1.9%), interstitial lung disease (1.9%), pneumonia (1.9%), pyrexia (1.6%), disease progression (1.2%).
The serious adverse event figures describe participants affected among those listed as at risk in each group. For trastuzumab deruxtecan, 49 of 257 participants at risk were affected; for T-DM1, 47 of 261 were affected. These are participant counts, not a comparison adjusted for follow-up time or other factors. No new percentages have been calculated from them.
The registry lists vomiting, interstitial lung disease and pneumonia at 1.9% each among the top serious adverse event terms for the trastuzumab deruxtecan group. Pyrexia is listed at 1.6%, and disease progression and urinary tract infection at 1.2% each. These term-level entries should not be interpreted as a complete account of every safety outcome. The registry record does not explain whether a participant could contribute to more than one term.
The adverse-event data also list deaths of 33 participants in the trastuzumab deruxtecan group and 53 in the T-DM1 group. These counts do not, on their own, identify cause or establish that deaths were treatment-related. The registry record does not provide attribution details alongside these figures. Serious adverse event counts and death counts should therefore be read as descriptive safety information, not as proof of causation or as a complete safety comparison.
12. What the Result Does, and Does Not, Mean
The registry record documents a randomized comparison of trastuzumab deruxtecan and T-DM1 in participants with HER2-positive, unresectable and/or metastatic breast cancer previously treated with trastuzumab and taxane. Its primary outcome was BICR-assessed PFS. The posted results include a T-DM1 median of 6.8 months with a 95% confidence interval from 5.6 to 8.2 months, and a lower confidence limit of 18.5 months for trastuzumab deruxtecan.
Those entries do not form a complete numerical comparison: the trastuzumab deruxtecan median and upper confidence limit are not reported in the registry record. Nor is a hazard ratio, p-value or other comparative analysis posted. The results therefore do not support calculation of a between-group difference or a determination of statistical significance from the reported PFS summaries alone.
General statistical explanation: a trial result is an estimate based on the participants and follow-up included in an analysis, and its uncertainty depends on the data and methods. A median does not describe every participant’s outcome, and it is not a guarantee of an individual’s experience. A confidence interval describes uncertainty about an estimate under the analysis procedure; it is not a prediction interval for individual outcomes.
The record also lists serious adverse event counts and selected serious event terms. These are descriptive figures and do not establish that a particular event was caused by treatment. The death counts likewise do not identify cause. The record does not post the comparative analyses for the secondary outcomes, including overall survival, objective response rate, duration of response and investigator-assessed PFS.
Accordingly, the posted information can be used to identify the trial design and the reported endpoint summaries, but it is not a complete basis for judging the comparative PFS effect or for making claims about treatment efficacy or safety. Those judgments would require the missing comparative estimates, fuller outcome reporting and sufficient information about analysis populations, follow-up and methods.
13. Why This Trial Matters Statistically
This trial illustrates why a randomized design and a complete comparative analysis are both important. Random assignment is intended to create groups suitable for comparison, while reporting the comparative effect and its uncertainty allows readers to assess what the observed data say. The registry record describes randomization and parallel treatment groups, but the posted primary endpoint results do not include a hazard ratio, p-value or complete median entry for both groups.
The endpoint also shows how assessment source can matter. The primary PFS outcome was determined by blinded independent central review, while investigator-assessed PFS was listed as a secondary outcome. Distinguishing these assessments makes clear that endpoint definition and review process are part of interpreting a trial result, especially in an open-label study.
The posted figures reinforce the difference between a group summary and a comparative effect. A median and its confidence interval summarize one group; they do not directly answer how the groups differ. For a time-to-event outcome, comparative estimates should be interpreted with information about event timing, follow-up and the analysis method. Those comparative results are not reported in the registry record.
Finally, the record lists several secondary outcomes and safety counts, but does not post analyses for the secondary outcomes. This highlights why outcome completeness, multiplicity plans and clear reporting of analysis populations matter. Without those details, a reader should keep conclusions proportional to the limited summaries available and avoid treating isolated figures as a full account of the trial’s evidence.
14. Limitations
- The posted summary statistics are the only data these results rest on; patient-level data, full protocols and statistical analysis plans are not available.
- Recalculated results are simple, unadjusted calculations from posted summaries. They do not replace the sponsor's prespecified analysis.
The main limitation for interpreting the primary result is incomplete reporting of the two-arm comparison. The T-DM1 median and confidence interval are posted, but the trastuzumab deruxtecan median is not reported in the registry record, and its upper confidence limit is absent. No hazard ratio, p-value, event count or other comparative PFS analysis is posted. The available entries therefore do not quantify the relative effect or its statistical uncertainty.
The record identifies the PFS analysis population as the Full Analysis Set and gives the data cut-off date, but does not define that population further or report the number of PFS events. Follow-up distribution, censoring details and missing-data handling are also not reported in the registry record. These omissions limit assessment of the information underlying the time-to-event summaries.
The study was open-label, although the primary endpoint was assessed by blinded independent central review. The registry does not provide further details on the BICR process or on agreement between central and investigator assessments. It also does not post results for the four listed secondary outcomes, including overall survival and investigator-assessed PFS.
The registry record does not report the multiplicity strategy, interim analyses, the trial’s own sample-size justification or a full statistical analysis plan. The safety figures are descriptive; event attribution and the relationship of deaths to treatment are not reported alongside the counts. These limitations concern what can be evaluated from the registry record and do not establish that the underlying study did or did not collect additional information.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: DS-8201a Versus T-DM1 for Human Epidermal Growth Factor Receptor 2 (HER2)-Positive, Unresectable and/or Metastatic Breast Cancer Previously Treated With Trastuzumab and Taxane [DESTINY-Breast03] — NCT03529110.
- Registry record last updated 2026-10-07; status last verified 2026-09.
- Results first posted 2022-04-29.
- Data retrieved from ClinicalTrials.gov on 2026-11-09.
- Group sizes, means, event counts and sponsor-reported p-values are reproduced as posted. Effect estimates, confidence intervals and p-values not attributed to the sponsor are independently calculated from the posted summary statistics.
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18. Record Summary
NCT03529110 is a completed phase 3, multicenter, randomized, open-label, active-controlled, parallel-group study sponsored by Daiichi Sankyo. It enrolled 524 participants with HER2-positive, unresectable and/or metastatic breast cancer previously treated with trastuzumab and taxane. The groups received trastuzumab deruxtecan, 5.4 mg/kg intravenously every 3 weeks, or T-DM1 in accordance with the approved label.
The primary outcome was median PFS by BICR, assessed in the Full Analysis Set at the 21 May 2021 data cut-off. The registry posts a T-DM1 median of 6.8 months (95% confidence interval 5.6 to 8.2 months). For trastuzumab deruxtecan, it reports a lower confidence limit of 18.5 months but no median or upper limit. No comparative hazard ratio, p-value or analysis entry is posted. Four secondary outcomes are listed, but their analyses are not reported in the registry record.