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 A Study to Evaluate the Efficacy and Safety of Trastuzumab Emtansine Versus the Combination of Trastuzumab Plus Docetaxel in Patients With HER2-positive Breast Cancer (NCT02144012), a randomized phase 3 study. The primary outcome is Progression-Free Survival (PFS).
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT02144012 |
| Phase | Phase 3 |
| Condition | Metastatic Breast Cancer |
| Allocation | Randomized |
| Design model | Parallel |
| Masking | None (open label) |
| Enrollment | 49 |
| Arms in the primary outcome | 2 |
| Lead sponsor | Hoffmann-La Roche |
| Results posted | Yes |
2. Clinical Question
Population
The study concerned people with HER2-positive breast cancer that was unresectable and locally advanced, recurrent or progressive after primary multimodality therapy, or metastatic without prior chemotherapy for metastatic disease. The record identifies metastatic breast cancer as the condition and describes the intent-to-treat population as all randomized participants analyzed according to assigned treatment. The registry does not give further participant characteristics in the results.
Intervention
Arm A received trastuzumab emtansine every three weeks. Treatment could continue until investigator-assessed disease progression, unacceptable toxicity, or sponsor study termination, whichever occurred first. The trial addressed this regimen as a first-line treatment option in the stated population.
Comparator
Arm B received trastuzumab plus docetaxel every three weeks. The registry says this comparator was selected because it represented a common first-line option in China and other Asia-Pacific countries. The comparison was randomized, parallel-group, and open-label.
Primary question
The primary endpoint was progression-free survival, defined as time from randomization to investigator-assessed disease progression or death from any cause, whichever occurred first. The central question was how the median time to this event was described in each assigned group at the clinical data cut-off, which was up to 20 months. The registry record does not report a sponsor hazard ratio or a formal between-group test for this endpoint.
3. Trial Design
This was a randomized, multicenter, multinational, open-label Phase III study with two parallel treatment groups. Its stated objective was to evaluate efficacy and safety of trastuzumab emtansine versus trastuzumab plus docetaxel as first-line treatment for HER2-positive progressive or recurrent locally advanced or metastatic breast cancer. The registry record lists enrollment of 49 participants. The study status is terminated, and the recorded start and primary completion dates are 2014-06 and 2016-01.
The planned allocation was 2:1 in favor of trastuzumab emtansine. The posted primary endpoint groups contain 34 participants in Arm A and 15 in Arm B. Both regimens were administered at in-clinic visits every three weeks during treatment. The record states that treatment could continue until investigator-assessed progression, unacceptable toxicity, or sponsor study termination. It does not report the reason for termination or the timing of that decision.
Participants and investigators were not masked to treatment assignment. This matters when interpreting investigator-assessed progression, because open-label knowledge can potentially influence assessment. It does not establish that such influence occurred, and the registry record does not describe any procedures to limit assessment bias.
The primary endpoint analysis population is defined as the intent-to-treat population: all randomized participants, grouped according to the treatment assigned at randomization. For the posted progression-free survival results, the arm sizes are consistent with the recorded randomized enrollment. The record does not provide a detailed account of follow-up completeness, protocol deviations, or how censoring was handled.
Other listed outcomes include overall survival, one-year survival, overall survival truncated at two years, objective response rate, duration of response, pharmacokinetics, immunogenicity, and patient-reported outcomes. The posted registry record includes an objective response rate result, but numerical results for the other named outcomes are not reported in the registry record. A detailed statistical analysis plan, sample-size justification, interim-analysis plan, and reasons for early termination are not reported in the registry record.
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.
Before assignment: Only 49 participants of the originally planned 561 participants were enrolled in the study at the time of study termination.
Overall Study
| Stage | Arm A: Trastuzumab Emtansine | Arm B: Trastuzumab + Docetaxel |
|---|---|---|
| STARTED | 34 | 15 |
| COMPLETED | 0 | 0 |
| NOT COMPLETED | 34 | 15 |
Reasons for not completing this period:
| Reason | Arm A: Trastuzumab Emtansine | Arm B: Trastuzumab + Docetaxel |
|---|---|---|
| Adverse Event | 1 | 0 |
| Death | 1 | 0 |
| Withdrawal by Subject | 11 | 3 |
| Study Terminated by Sponsor | 18 | 12 |
| Other | 3 | 0 |
Analysis population for the primary outcome, as defined in the registry: The intent-to-treat (ITT) population included all randomized participants grouped according to the treatment assigned at randomization.
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: The intention-to-treat (ITT) population included all randomized participants grouped according to the treatment assigned at randomization.
| Characteristic | Unit | Arm A: Trastuzumab Emtansine | Arm B: Trastuzumab + Docetaxel | Total |
|---|---|---|---|---|
| Participants analysed | 34 | 15 | 49 | |
| Age, Continuous | years | 53.7 (SD 9.5) | 51.7 (SD 11.1) | 53.1 (SD 9.9) |
| Sex: Female, Male: Female | Participants | 34 | 15 | 49 |
| Sex: Female, Male: Male | Participants | 0 | 0 | 0 |
6. Primary Endpoint
The registry lists the primary outcome as Progression-Free Survival (PFS), measured over At time of clinical data cut-off (up to 20 months).
| Element | Registry entry |
|---|---|
| Result type | Median |
| Measure of spread | 95% Confidence Interval |
| Unit | months |
| Endpoint classification | Time-to-Event Analysis |
Progression-free survival (PFS) measures the time from randomization until the first of disease progression or death from any cause. In this study, progression was based on investigator assessment and defined using RECIST v1.1: at least a 20% increase in the sum of target-lesion diameters with an absolute increase of at least 5 millimeter, or the appearance of one or more new lesions. The endpoint therefore combines radiographic progression and death into a single time-to-event outcome.
The registry reports median PFS in months, with a 95% confidence interval, at the clinical data cut-off, described as up to 20 months. A median is the time by which half of the analyzed group is estimated to have experienced the event and half to remain event-free. It summarizes the center of a time-to-event distribution without describing every participant’s course or the full shape of the survival curve.
PFS is used in oncology trials because it captures time until progression or death, rather than relying only on whether a participant ever responds. However, the measure depends on assessment timing, event definitions, follow-up, and handling of participants whose event status is not observed during follow-up. Those details are not fully reported in the registry record. The primary result is investigator-assessed and open-label, so it should be read with those design features in mind.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
Median PFS was 10.3 months in the trastuzumab emtansine group, with a 95% confidence interval from 4.2 months to an upper limit that is not reported. In the trastuzumab plus docetaxel group, median PFS was 8.2 months, with a 95% confidence interval from 6.0 to 13.8 months. These are separate arm summaries. The registry record does not report a hazard ratio, confidence interval for a relative effect, or formal statistical test for the primary endpoint, so the arm medians alone do not establish the magnitude or statistical certainty of a treatment contrast.
A confidence interval describes uncertainty in an estimated quantity under the statistical method used. The intervals for the two medians are not a substitute for a confidence interval for the difference between arms. In particular, comparing whether separate intervals overlap is not a formal test of the randomized treatment contrast. The missing upper confidence limit for the trastuzumab emtansine median further limits how fully that arm’s median precision can be described.
The trial was terminated, and enrollment was 49. The registry record does not report the reason for termination, a planned sample size, or whether the termination affected follow-up or outcome ascertainment. Those omissions matter for interpretation: a small enrolled group and incomplete information about follow-up may make estimates less precise, but the record does not allow a quantified assessment of that possibility. No sponsor-reported primary comparison is available to take precedence over or contextualize a recalculation.
The secondary objective response rate results describe the proportion of participants with a response in each arm, and the registry also posts an unadjusted comparison. These data address a different outcome from time to progression or death. The unadjusted p-value is 0.154; it should not be interpreted as proof of equivalence or as a definitive result, especially because the registry record does not report a multiplicity strategy or a formal analysis plan. The registry lists other secondary outcomes, but their numerical results are not reported in the registry record.
Safety summaries show serious adverse events in both groups, as well as other adverse events. The group sizes are unequal, and the record’s serious-event term list does not specify treatment assignment for each term. These figures describe events recorded in the study; they do not by themselves establish comparative safety or causation. Taken together, the posted results provide descriptive arm-level estimates, with important limits on formal comparative inference.
9. Statistical Methods Explained
What does a median time-to-event result mean?
Progression-free survival is a time-to-event endpoint: the event is the first occurrence of progression or death. In general, time-to-event methods are designed to use information from participants who have different lengths of follow-up, including those whose event has not been observed by the time observation ends. Such participants may be censored, meaning their event-free time is known up to a point but their later status is not known. The registry record does not report the censoring rules or the method used to estimate the medians, so details beyond the posted endpoint definition cannot be established.
A median is a distributional summary, not an average duration for every participant and not a statement that all participants experienced an event at that time. It does not show the complete course of the estimated event-free experience. Two medians alone also do not describe how the groups compare over the whole follow-up period; a relative time-to-event measure such as a hazard ratio would address a different aspect of the comparison. No sponsor-reported hazard ratio for PFS is reported in the registry record.
How should confidence intervals be read?
In general, a confidence interval expresses the uncertainty associated with an estimate under a specified procedure. A wider interval indicates less precision than a narrower interval, all else equal. The posted PFS results include 95% confidence intervals for the arm medians, but the upper limit for the trastuzumab emtansine median is not reported. The intervals refer to each median separately; they do not directly estimate the difference or relative effect between randomized groups. An interval crossing or not crossing a particular value should not be used to infer a treatment comparison unless the relevant contrast and its uncertainty are reported.
The primary results use investigator assessments in an open-label trial. In general, knowledge of assignment can affect subjective decisions or assessment processes. The endpoint’s RECIST-based definition gives a stated progression criterion, but the record does not report whether imaging was independently reviewed or whether any other masking safeguards were used. It is therefore appropriate to note the assessment context without assuming that it caused bias.
What does the response-rate comparison add?
Objective response rate is a binary outcome: each participant is classified according to whether a response was recorded under the endpoint definition. The registry posts response proportions with confidence intervals and an unadjusted comparison. The comparison includes a risk difference and also ratio measures, but these recalculated summaries are not the sponsor’s reported analysis. In general, a risk difference expresses the difference between proportions, while a ratio compares them on a relative scale. The registry’s unadjusted p-value is 0.154. A p-value measures how compatible the observed data are with a specified null model under the test assumptions; it is not the probability that the null hypothesis is true, nor does it measure clinical importance.
The response-rate denominators differ from the randomized group sizes: the posted endpoint counts are 27 in Arm A and 14 in Arm B, compared with 34 and 15 randomized participants. The registry record does not report why these denominators differ, how participants without an evaluable response were handled, or whether missing responses were imputed. Consequently, the response-rate estimates should be interpreted as reported, without assuming that the analysis included every randomized participant.
How should planning illustrations be distinguished from observed results?
Sample-size planning illustrations use the observed response-rate effect as an input and show hypothetical participants per arm under stated assumptions. The registry description specifies a two-sided significance level of 0.05, equal allocation, a normal approximation, and effect sizes defined as fractions of the observed effect. For planning at 100% of the observed effect, the illustration gives 69 participants per arm for 80% power and 92 for 90% power. For planning at 75% of the observed effect, the figures are 126 and 167; at 50%, they are 287 and 384.
These are planning illustrations, not the trial’s original design justification and not observed power. They do not show that the trial was designed using these assumptions. The registry record does not report the trial’s own sample-size justification. In general, observed-effect-based planning can be optimistic if the observed effect is imprecise or unusually large; using smaller fractions illustrates how required sample sizes change under less pronounced assumed effects. The record’s illustration assumes equal allocation, whereas the stated randomization plan was 2:1, so the illustration is not a reconstruction of the trial’s allocation plan.
Why do over-dispersion and multiplicity matter in general?
Over-dispersion arises when variability in count data is greater than a simple statistical model expects. In general, ignoring it can make uncertainty look too small and inference too confident. It is not the central modeling issue for the posted median PFS or binary response summaries, and the registry record does not report an over-dispersion analysis. Multiple testing arises when several outcomes or comparisons are examined; without an appropriate strategy, the chance of at least one apparently notable result can increase. The registry lists several secondary outcomes, but its multiplicity procedure is not reported in the registry record. The unadjusted response comparison therefore has less confirmatory weight than a prespecified primary analysis with a documented multiplicity approach.
10. Multiplicity, Missing Data and Analysis Populations
The registry identifies an intent-to-treat population for PFS, comprising all randomized participants analyzed according to assigned treatment. This preserves the randomized comparison in the endpoint definition. It does not, by itself, explain how censoring or missing assessments were handled. Those details are not reported in the registry record.
The response-rate results use 27 participants in the trastuzumab emtansine group and 14 in the trastuzumab plus docetaxel group, while the randomized arm counts are 34 and 15. The record does not explain the difference in denominators, report the disposition of participants without an evaluable response, or state whether any missing outcomes were imputed. The extent and direction of any resulting bias cannot be determined from the posted information.
The study lists multiple secondary outcomes, but a multiplicity strategy is not reported in the registry record. The response-rate comparison is labeled unadjusted, and the registry reports no analyses for the primary endpoint comparison. A protocol-defined testing hierarchy, adjustment method, or distinction between confirmatory and exploratory analyses is not reported. Without that information, the secondary p-value should not be treated as if it were an adjusted confirmatory test.
The registry record also does not report a detailed statistical analysis plan, interim analyses, sample-size justification, or reasons for termination. These are unknowns, not evidence that the study did or did not use particular procedures. The posted PFS analysis population is defined, but equivalent population and missing-data details for all secondary outcomes are not reported. This limits independent assessment of selection, follow-up, and multiplicity, and it makes the arm-level descriptions more informative than any broad claim of comparative certainty.
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 |
|---|---|---|---|
| Arm A: Trastuzumab Emtansine | 8 | 34 | 23.5% |
| Arm B: Trastuzumab + Docetaxel | 5 | 15 | 33.3% |
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 |
|---|---|
| Arm A: Trastuzumab Emtansine | 31 of 34 |
| Arm B: Trastuzumab + Docetaxel | 15 of 15 |
Most frequent serious adverse event terms
| Event term | Organ system | Arm A: Trastuzumab Emtansine | Arm B: Trastuzumab + Docetaxel |
|---|---|---|---|
| Febrile neutropenia | Blood and lymphatic system disorders | 0 of 34 | 3 of 15 |
| Neutropenia | Blood and lymphatic system disorders | 1 of 34 | 2 of 15 |
| Pneumonia | Infections and infestations | 2 of 34 | 1 of 15 |
| Pyrexia | General disorders | 2 of 34 | 0 of 15 |
| Post procedural cellulitis | Infections and infestations | 0 of 34 | 1 of 15 |
| Infusion related reaction | Injury, poisoning and procedural complications | 1 of 34 | 0 of 15 |
| Hyperammonaemia | Metabolism and nutrition disorders | 1 of 34 | 0 of 15 |
| Normal pressure hydrocephalus | Nervous system disorders | 0 of 34 | 1 of 15 |
| Vaginal haemorrhage | Reproductive system and breast disorders | 1 of 34 | 0 of 15 |
| Interstitial lung disease | Respiratory, thoracic and mediastinal disorders | 1 of 34 | 0 of 15 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Arm A: Trastuzumab Emtansine | Arm B: Trastuzumab + Docetaxel |
|---|---|---|---|
| Myalgia | Musculoskeletal and connective tissue disorders | 11 of 34 | 8 of 15 |
| Diarrhoea | Gastrointestinal disorders | 7 of 34 | 11 of 15 |
| Upper respiratory tract infection | Infections and infestations | 13 of 34 | 4 of 15 |
| Headache | Nervous system disorders | 11 of 34 | 5 of 15 |
| Peripheral sensory neuropathy | Nervous system disorders | 8 of 34 | 8 of 15 |
| Nausea | Gastrointestinal disorders | 11 of 34 | 3 of 15 |
| Alopecia | Skin and subcutaneous tissue disorders | 2 of 34 | 10 of 15 |
| Fatigue | General disorders | 9 of 34 | 1 of 15 |
| Cough | Respiratory, thoracic and mediastinal disorders | 10 of 34 | 0 of 15 |
| Aspartate aminotransferase increased | Investigations | 8 of 34 | 1 of 15 |
Serious events with the highest arm-level rate: febrile neutropenia (20.0%), neutropenia (13.3%), pneumonia (6.7%), post procedural cellulitis (6.7%), normal pressure hydrocephalus (6.7%).
The registry reports serious adverse events for 8 of 34 participants in the trastuzumab emtansine group and 5 of 15 participants in the trastuzumab plus docetaxel group. It also reports other adverse events for 31 of 34 and 15 of 15 participants, respectively. These are counts of participants with events in the registry’s groupings, not estimates of a causal treatment effect. The groups differ in size, and direct comparison of raw counts would not account for that difference.
The serious adverse event terms listed include febrile neutropenia, neutropenia, pneumonia, post procedural cellulitis, normal pressure hydrocephalus, and pyrexia, with percentages shown in the registry. The list does not identify the treatment arm associated with each term or describe the denominator used for each percentage. The terms should not be assigned to a group or interpreted as comparative rates without that information.
In general, adverse events recorded during a trial may have different levels of severity, timing, and attribution. The registry record does not report event-related deaths, and the death counts are not available. These summaries describe what was posted, but they do not establish that a drug caused an event or support a complete between-group safety comparison.
12. What the Result Does, and Does Not, Mean
The posted primary results describe estimated median progression-free survival in each randomized group. They show that the recorded median was 10.3 months for trastuzumab emtansine and 8.2 months for trastuzumab plus docetaxel. The confidence interval for the first median has a reported lower limit but no reported upper limit; the second median has a reported interval from 6.0 to 13.8 months. These summaries convey arm-level timing and precision, not a formal estimate of the treatment contrast.
The registry does not report a PFS hazard ratio, a confidence interval for a between-arm effect, or a formal primary comparison. The medians alone therefore do not establish whether the groups differ statistically, how any difference behaves across follow-up, or whether an observed difference is clinically important. Nor does a lack of a reported test establish no difference. The record’s open-label design and investigator assessment are relevant context, while the available details are insufficient to quantify any effect of those features.
The response-rate result is a separate, unadjusted secondary analysis with smaller analysis denominators than the randomized group sizes. The p-value of 0.154 does not prove that the treatments are equivalent, and it does not settle the primary time-to-event question. Other listed secondary outcome results are not reported in the registry record, and there is no reported multiplicity strategy to support a collection of confirmatory secondary claims.
The safety figures describe participants with reported events, but the listed serious-event terms are not linked to treatment groups, and no event-related death counts are reported. These data do not establish causation or provide a complete comparative safety assessment.
Overall, the record supports a descriptive account of the randomized groups and their posted outcomes. It does not support a definitive claim that one regimen is superior, equivalent, or safer. Such claims would require comparative estimates and uncertainty, fuller outcome reporting, and clearer documentation of analysis populations, missing data, follow-up, and prespecified statistical methods.
13. Why This Trial Matters Statistically
This trial illustrates why arm-level estimates and comparative inference are not the same. A median for each group is useful for describing the observed time-to-event experience, but the treatment question is fundamentally about the contrast between groups. A reported hazard ratio or another prespecified contrast, together with its uncertainty and analysis method, would directly address that question. The registry record does not report such a primary comparison.
The study also shows how a nominally large trial phase can end with limited enrollment. It is recorded as a Phase III randomized study with 49 participants and a terminated status. The record does not provide the reason for termination or the planned sample-size justification, so the effect of termination on precision and follow-up cannot be reconstructed. The modest enrollment is especially relevant when interpreting confidence intervals and smaller secondary analysis populations.
Open-label treatment and investigator-assessed progression are important design details, not automatic evidence of bias. The stated RECIST definition makes the event criterion explicit, but missing information about review procedures limits assessment of how assessments were protected from knowledge of assignment. Clear reporting of endpoint ascertainment and analysis procedures is essential for readers to distinguish a defined outcome from a fully documented comparison.
Finally, the record lists multiple secondary outcomes but does not report a multiplicity plan, detailed statistical analysis plan, or most secondary numerical results. A single unadjusted secondary comparison should not be asked to carry confirmatory weight in that setting. For biostatistical interpretation, this case emphasizes the value of reporting prespecified estimands, analysis populations, missing-data handling, effect estimates, confidence intervals, and the rationale for stopping a trial.
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.
Several limitations are specific to the record. Enrollment was 49, and the study status is terminated, but the reason for termination and any impact on planned follow-up are not reported in the registry record. The record also does not provide the sponsor’s sample-size justification, so it is not possible to assess the intended precision or power of the original design from the posted information.
The primary endpoint is investigator-assessed in an open-label study. Although the progression definition refers to RECIST v1.1, the registry record does not report whether imaging was independently reviewed, how assessment schedules were implemented, or how disagreements were handled. It also does not provide a primary hazard ratio or formal treatment comparison, and one confidence limit for the trastuzumab emtansine median is not reported.
For objective response rate, the analysis denominators are smaller than the randomized groups. Reasons for the smaller counts, response-evaluation rules beyond the posted result, and missing-data handling are not reported in the registry record. The unadjusted comparison has no reported multiplicity context. Numerical results for the other listed secondary outcomes are not reported, limiting the ability to assess consistency across outcomes.
The safety record provides group counts for serious and other adverse events, but does not report deaths in the posted safety summary or assign the listed serious-event terms to arms. The registry record also does not report detailed analysis methods, interim analyses, or a statistical analysis plan. These gaps restrict independent evaluation; they do not establish that a particular procedure was absent or that the findings are biased.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: A Study to Evaluate the Efficacy and Safety of Trastuzumab Emtansine Versus the Combination of Trastuzumab Plus Docetaxel in Patients With HER2-positive Breast Cancer — NCT02144012.
- Registry record last updated 2017-03-07; status last verified 2017-01.
- Results first posted 2017-03-07.
- 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
NCT02144012 is a randomized, open-label, parallel-group Phase III study comparing trastuzumab emtansine with trastuzumab plus docetaxel as first-line treatment for HER2-positive advanced or metastatic breast cancer. The registry records enrollment of 49 participants and a terminated status. The primary endpoint is investigator-assessed progression-free survival, defined as time from randomization to progression or death.
Median PFS was 10.3 months in Arm A and 8.2 months in Arm B. A confidence interval upper limit for Arm A and a formal between-group primary comparison are not reported in the registry record. The registry also posts an unadjusted objective response rate comparison and adverse-event counts. Reasons for termination, a detailed statistical analysis plan, multiplicity procedures, and missing-data handling are not reported in the registry record. The posted findings are descriptive and do not establish a definitive comparative conclusion.