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 of Trastuzumab Emtansine, Paclitaxel, and Pertuzumab in Patients With HER2-Positive, Locally Advanced or Metastatic Breast Cancer (NCT00951665), a randomized phase 1, phase 2 study. The primary outcome is Number of Participants With Any Adverse Events (AEs), Serious Adverse Events (SAEs), AEs of Grades 3/4, and Death.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT00951665 |
| Phase | Phase 1, Phase 2 |
| Condition | Metastatic Breast Cancer |
| Allocation | Randomized |
| Design model | Parallel |
| Masking | None (open label) |
| Enrollment | 107 |
| Arms in the primary outcome | n/a |
| Lead sponsor | Genentech, Inc. |
| Results posted | Yes |
2. Clinical Question
Population
Participants had HER2-positive, locally advanced or metastatic breast cancer. The condition field identifies metastatic breast cancer, while the study description also includes locally advanced disease. The safety population is defined as participants who received at least a single dose of study medication. The record reports enrollment of 107, but does not give the number who received treatment in each regimen in the narrative description.
Intervention
The study evaluated intravenous trastuzumab emtansine (T-DM1) and paclitaxel, with pertuzumab included in some regimens. Phase Ib tested weekly or every-three-weeks schedules and combinations, while Phase IIa included groups receiving the maximum tolerated dose identified in Phase Ib, with or without pertuzumab. The registry describes the study as a dose-escalation evaluation of safety, tolerability, pharmacokinetics and feasibility.
Comparator
The record identifies randomized parallel assignment and describes six regimens across Phase Ib and Phase IIa. It does not report the allocation process, the specific comparisons planned between regimens, or whether the comparisons were designed to support formal claims of superiority or equivalence. The arms should therefore be read as distinct dose and combination groups rather than as a single, clearly specified treatment-versus-control contrast.
Primary question
The primary outcome concerns the number of participants with adverse events, serious adverse events, adverse events of Grades 3/4, and death. The safety observation period runs up to 30 days after the last dose of study treatment or study discontinuation or termination, whichever is later. The registry record does not report a single inferential comparison for this multi-part endpoint. The posted group counts describe observed safety events, but do not establish comparative treatment effects.
3. Trial Design
This is a Phase Ib-IIa, multi-institutional, open-label study with randomized parallel assignment. The registry lists enrollment of 107 and a completed status. It gives a start date of 2009-08 and a primary completion date of 2012-02. Masking is listed as none. Although randomization is recorded, the allocation procedure, any stratification factors, and the number assigned to each regimen are not reported in the registry record.
The Phase Ib part used dose escalation and included four regimens. Participants received T-DM1 every three weeks with weekly paclitaxel, the same combination with pertuzumab every three weeks, weekly T-DM1 with weekly paclitaxel, or that weekly combination with pertuzumab every three weeks. Phase IIa included two groups receiving the maximum tolerated dose identified in Phase Ib: T-DM1 3.6mg/kg every three weeks plus paclitaxel 80mg/m\^2 weekly, with or without pertuzumab every three weeks. All listed drugs were administered intravenously.
The study’s stated aims included safety, tolerability, pharmacokinetics and feasibility. Secondary outcomes listed in the registry include objective response rate, duration of objective response, clinical benefit and progression-free survival. The record does not describe the statistical methods used to select the dose, the rules for moving between dose levels, or how the randomized regimen groups were intended to be compared. Those design details are not reported in the registry record, so the listed arms alone do not establish a prespecified primary contrast.
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.
Phase 1b
| Stage | Phase Ib Regimen 1 | Phase Ib Regimen 2 | Phase Ib Regimen 3 | Phase Ib Regimen 4 | Phase IIa Group A | Phase IIa Group B |
|---|---|---|---|---|---|---|
| STARTED | 29 | 10 | 21 | 3 | 0 | 0 |
| Started Treatment | 26 | 10 | 21 | 3 | 0 | 0 |
| COMPLETED | 7 | 6 | 4 | 2 | 0 | 0 |
| NOT COMPLETED | 22 | 4 | 17 | 1 | 0 | 0 |
Reasons for not completing this period:
| Reason | Phase Ib Regimen 1 | Phase Ib Regimen 2 | Phase Ib Regimen 3 | Phase Ib Regimen 4 | Phase IIa Group A | Phase IIa Group B |
|---|---|---|---|---|---|---|
| Adverse Event | 2 | 1 | 0 | 1 | 0 | 0 |
| Death | 1 | 0 | 2 | 0 | 0 | 0 |
| Physician Decision | 4 | 0 | 1 | 0 | 0 | 0 |
| Withdrawal by Subject | 0 | 1 | 0 | 0 | 0 | 0 |
| Disease Progression | 13 | 2 | 14 | 0 | 0 | 0 |
| Protocol Violation | 2 | 0 | 0 | 0 | 0 | 0 |
Phase 2a
| Stage | Phase Ib Regimen 1 | Phase Ib Regimen 2 | Phase Ib Regimen 3 | Phase Ib Regimen 4 | Phase IIa Group A | Phase IIa Group B |
|---|---|---|---|---|---|---|
| STARTED | 0 | 0 | 0 | 0 | 22 | 22 |
| COMPLETED | 0 | 0 | 0 | 0 | 10 | 15 |
| NOT COMPLETED | 0 | 0 | 0 | 0 | 12 | 7 |
Reasons for not completing this period:
| Reason | Phase Ib Regimen 1 | Phase Ib Regimen 2 | Phase Ib Regimen 3 | Phase Ib Regimen 4 | Phase IIa Group A | Phase IIa Group B |
|---|---|---|---|---|---|---|
| Adverse Event | 0 | 0 | 0 | 0 | 2 | 0 |
| Death | 0 | 0 | 0 | 0 | 1 | 1 |
| Lost to Follow-up | 0 | 0 | 0 | 0 | 1 | 0 |
| Physician Decision | 0 | 0 | 0 | 0 | 0 | 1 |
| Withdrawal by Subject | 0 | 0 | 0 | 0 | 2 | 0 |
| Disease Progression | 0 | 0 | 0 | 0 | 6 | 5 |
Analysis population for the primary outcome, as defined in the registry: Safety Population: All participants who received at least a single dose of study medication were included.
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.
Only the first 6 of 7 groups are shown.
| Characteristic | Unit | Phase Ib Regimen 1 | Phase Ib Regimen 2 | Phase Ib Regimen 3 | Phase Ib Regimen 4 | Phase IIa Group A | Phase IIa Group B |
|---|---|---|---|---|---|---|---|
| Participants analysed | 26 | 10 | 21 | 3 | 22 | 22 | |
| Age, Continuous | years | 53.3 (SD 12.3) | 51.3 (SD 11.9) | 54.1 (SD 8.5) | 49.3 (SD 4.0) | 51.7 (SD 11.8) | 55.1 (SD 7.7) |
| Sex: Female, Male: Female | Participants | 26 | 10 | 19 | 3 | 21 | 22 |
| Sex: Female, Male: Male | Participants | 0 | 0 | 2 | 0 | 1 | 0 |
6. Primary Endpoint
The registry lists the primary outcome as Number of Participants With Any Adverse Events (AEs), Serious Adverse Events (SAEs), AEs of Grades 3/4, and Death, measured over Up to 30 days after the last dose of study treatment or study discontinuation/termination, whichever is later.
| Element | Registry entry |
|---|---|
| Result type | Number |
| Measure of spread | not applicable |
| Unit | participants |
| Endpoint classification | Binary Endpoint |
The primary outcome is the number of participants with any adverse events, serious adverse events, adverse events of Grades 3/4, and death. An adverse event is defined as an untoward medical occurrence temporally associated with use of a medicinal product, whether or not it is considered related to that product. A serious adverse event is defined using consequences such as death, life-threatening events, hospitalization or its prolongation, disability or incapacity, or a congenital anomaly or birth defect.
The endpoint is used to describe safety during treatment and follow-up, rather than to measure tumor response. Its timeframe extends up to 30 days after the last dose or study discontinuation or termination, whichever is later. The registry defines the safety population as all participants who received at least a single dose of study medication. A count of participants with an event can communicate how many people experienced an outcome, but it does not by itself describe event severity, duration, recurrence, or causal relation to a study drug.
The primary outcome combines several event categories, and the posted record does not provide one consolidated comparison across regimens. The group-level safety figures should therefore be interpreted as descriptive counts, not as a single estimate of relative risk or treatment effect.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The record supports a descriptive reading of adverse-event counts across six named regimen groups. For serious adverse events, it reports 7 of 26 participants in Phase Ib Regimen 1, 5 of 10 in Phase Ib Regimen 2, 7 of 21 in Phase Ib Regimen 3, 2 of 3 in Phase Ib Regimen 4, 6 of 22 in Phase IIa Group A and 6 of 22 in Phase IIa Group B. The posted figures for other adverse events are 26 of 60, 10 of 10, 21 of 21, 3 of 3, 22 of 22 and 22 of 22, respectively. These are observed counts within the group-specific denominators; they are not adjusted comparisons.
The figures should not be read as a ranking of regimens. Group sizes differ, including a very small denominator in Phase Ib Regimen 4, and the regimens vary in dose schedule and in whether pertuzumab was included. The record does not report a statistical comparison, confidence intervals, or an adjustment for differences between groups. Nor does it describe whether groups were comparable at baseline. Without those elements, a difference in counts cannot be attributed to a regimen or interpreted as evidence that one regimen has a higher or lower risk.
The primary endpoint also names adverse events of Grades 3/4 and death, but the posted group summary does not provide separate group counts for either category. Death values are absent in the group information. The record’s listed serious-event terms include Neutropenia, Thrombosis in device and Epistaxis at 33.3% each, Pneumonia at 20.0%, and Thrombocytopenia and Gastroenteritis at 10.0% each. The denominator and method used to calculate these percentages are not explained in the registry record, so they should not be treated as rates among all enrolled participants or as comparative estimates.
The registry lists secondary outcomes related to tumor response and progression, but provides no analyses for the posted outcome measures. Accordingly, these data do not establish the size or precision of an efficacy effect. A missing inferential result is not evidence of no effect; it means that the corresponding estimate cannot be evaluated from the registry record. The available safety counts are informative as descriptions of observed events, but support no causal or comparative conclusion by themselves.
9. Statistical Methods Explained
What do the counts represent?
For a binary safety outcome, a participant is classified according to whether the event occurred during the defined observation period. The count is the number classified with the event, and the denominator is the number of participants at risk for that reported group outcome. A count alone is not a rate unless its denominator and the relevant observation period are understood. The record supplies group denominators for serious and other adverse events, but the posted figures do not provide event-level timing or duration.
These summaries are descriptive. General statistical principle: a proportion from a group is an estimate based on the participants observed, and its precision depends in part on the amount of information in that group. Small groups tend to yield less precise estimates, so a single participant can have a larger influence on a small-group proportion than on a larger-group proportion. The 3-participant denominator for Phase Ib Regimen 4 makes that group especially difficult to compare reliably with the larger groups. This is a limitation of interpreting the observed counts, not a calculation of an unreported interval.
Why is a direct comparison not available?
A comparative analysis needs a defined contrast, an outcome definition, an analysis population and a statistical method. The registry reports randomized parallel assignment but does not report the allocation details or a planned comparison among the six regimens. It also identifies a primary outcome spanning several categories. The posted record has no analyses for the outcome measures and does not provide p-values, confidence intervals, adjusted estimates or a model specification. As a result, it is not possible to judge the magnitude or precision of a comparative effect from the posted counts.
General statistical principle: a confidence interval describes a range of values compatible with an estimate under a specified statistical model and sampling assumptions. It conveys uncertainty that a point estimate alone cannot show. No confidence intervals are reported for these group counts in the registry record. Likewise, a p-value would address compatibility with a specified null hypothesis under a chosen analysis; it would not measure clinical importance or establish causation. No such p-values are posted for the safety comparisons.
How should the sample-size assumptions be understood?
The record describes a planning illustration based on an observed effect, with a two-sided significance level of 0.05, equal allocation between two arms and a normal approximation. The effect to detect is defined as a stated fraction of the observed effect. For time-to-event outcomes, the stated planning approach uses a total number of events; for other outcomes, it expresses sample size as participants per arm. These are planning assumptions, not evidence that the study was designed or powered using those assumptions.
General statistical principle: a sample-size calculation is conditional on assumptions about the target effect, variability or event frequency, significance level, allocation and analysis. Changing those assumptions changes the planning result. A calculation based on an observed effect is a hypothetical planning illustration; it is not observed power and does not show that the trial had a particular probability of detecting an effect. The registry record does not report the original protocol’s sample-size justification, so the illustration cannot be taken as the trial’s own design rationale.
The primary safety endpoint contains several categories or time points and is not reduced to one comparison in the registry record. Therefore, there is no single observed contrast in the posted results from which to interpret a sample-size illustration as a definitive planning target for that primary endpoint. The record does not report the effect-size definition used for a particular safety comparison, nor a prespecified analysis that resolves the multiple endpoint categories.
What remains unknown about the analysis?
The registry does not report whether the primary safety summaries were adjusted, how missing observations were handled, or whether participants were analyzed according to assigned regimen or treatment received. It does define the safety population as participants receiving at least a single dose. The record also does not describe handling of repeated events, exposure time, treatment discontinuation, or changes in dose. These omissions matter because participant counts do not convey how long each person was observed or how many events an individual experienced.
General statistical principle: when follow-up duration differs, simple proportions may not capture differences in time at risk. Event-rate methods can incorporate time, but require suitable information and assumptions. No person-time analysis or event-rate estimate is reported in the registry record. The posted summaries should consequently be read as the reported participant counts and denominators, not as exposure-adjusted rates.
10. Multiplicity, Missing Data and Analysis Populations
The primary outcome names multiple safety categories: any adverse events, serious adverse events, adverse events of Grades 3/4, and death. Secondary outcomes include objective response rate, duration of objective response, clinical benefit and progression-free survival. Testing many outcomes or making many pairwise comparisons can increase the chance of a false-positive finding if the analyses are treated as independent opportunities to claim a result. General statistical principle: multiplicity can be addressed through prespecified testing hierarchies, adjusted significance thresholds or other methods, but the appropriate approach depends on the study’s objectives and analysis plan.
The registry record does not report a multiplicity strategy, a hierarchy of outcomes, or which comparisons were prespecified. It reports no analyses for the outcome measures, so there are no posted inferential findings from which to assess multiplicity adjustments. The primary safety endpoint is not reduced to one comparison in the registry record.
The safety population includes participants who received at least a single dose of study medication. The record does not state how missing safety observations were handled, whether any participants lacked follow-up, or how the analysis accounted for treatment discontinuation. It also does not report missing-data methods for the secondary outcomes. Missing data could affect interpretation if the likelihood of missingness were related to health status or treatment experience; whether that occurred is not reported in the registry record.
The registry lists randomized assignment, but the analysis population and the handling of participants who did not follow assigned treatment are not described. There is therefore no basis for asserting an intention-to-treat analysis or another particular analysis set. General statistical principle: defining analysis populations in advance helps clarify which participants contribute to each estimate and what question an estimate addresses. Here, the safety population definition is stated, but the analysis populations for other outcomes and the detailed analysis plan are not reported in the registry record.
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 |
|---|---|---|---|
| Phase Ib Regimen 1 | 7 | 26 | 26.9% |
| Phase Ib Regimen 2 | 5 | 10 | 50.0% |
| Phase Ib Regimen 3 | 7 | 21 | 33.3% |
| Phase Ib Regimen 4 | 2 | 3 | 66.7% |
| Phase IIa Group A | 6 | 22 | 27.3% |
| Phase IIa Group B | 6 | 22 | 27.3% |
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 |
|---|---|
| Phase Ib Regimen 1 | 26 of 60 |
| Phase Ib Regimen 2 | 10 of 10 |
| Phase Ib Regimen 3 | 21 of 21 |
| Phase Ib Regimen 4 | 3 of 3 |
| Phase IIa Group A | 22 of 22 |
| Phase IIa Group B | 22 of 22 |
Most frequent serious adverse event terms
| Event term | Organ system | Phase Ib Regimen 1 | Phase Ib Regimen 2 | Phase Ib Regimen 3 | Phase Ib Regimen 4 | Phase IIa Group A | Phase IIa Group B |
|---|---|---|---|---|---|---|---|
| Pneumonia | Infections and infestations | 0 of 26 | 2 of 10 | 2 of 21 | 0 of 3 | 0 of 22 | 0 of 22 |
| Nausea | Gastrointestinal disorders | 1 of 26 | 0 of 10 | 0 of 21 | 0 of 3 | 1 of 22 | 1 of 22 |
| Cellulitis | Infections and infestations | 2 of 26 | 0 of 10 | 1 of 21 | 0 of 3 | 0 of 22 | 0 of 22 |
| Gastroenteritis | Infections and infestations | 1 of 26 | 1 of 10 | 0 of 21 | 0 of 3 | 1 of 22 | 0 of 22 |
| Thrombocytopenia | Blood and lymphatic system disorders | 0 of 26 | 1 of 10 | 0 of 21 | 0 of 3 | 1 of 22 | 0 of 22 |
| Fatigue | General disorders | 0 of 26 | 0 of 10 | 0 of 21 | 0 of 3 | 1 of 22 | 1 of 22 |
| Sepsis | Infections and infestations | 0 of 26 | 0 of 10 | 2 of 21 | 0 of 3 | 0 of 22 | 0 of 22 |
| Muscular weakness | Musculoskeletal and connective tissue disorders | 1 of 26 | 0 of 10 | 0 of 21 | 0 of 3 | 0 of 22 | 1 of 22 |
| Febrile neutropenia | Blood and lymphatic system disorders | 1 of 26 | 0 of 10 | 0 of 21 | 0 of 3 | 0 of 22 | 0 of 22 |
| Neutropenia | Blood and lymphatic system disorders | 0 of 26 | 0 of 10 | 0 of 21 | 1 of 3 | 0 of 22 | 0 of 22 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Phase Ib Regimen 1 | Phase Ib Regimen 2 | Phase Ib Regimen 3 | Phase Ib Regimen 4 | Phase IIa Group A | Phase IIa Group B |
|---|---|---|---|---|---|---|---|
| Neuropathy peripheral | Nervous system disorders | 22 of 60 | 8 of 10 | 18 of 21 | 3 of 3 | 20 of 22 | 19 of 22 |
| Fatigue | General disorders | 23 of 60 | 8 of 10 | 18 of 21 | 2 of 3 | 16 of 22 | 19 of 22 |
| Alopecia | Skin and subcutaneous tissue disorders | 10 of 60 | 6 of 10 | 8 of 21 | 1 of 3 | 6 of 22 | 11 of 22 |
| Epistaxis | Respiratory, thoracic and mediastinal disorders | 9 of 60 | 6 of 10 | 9 of 21 | 2 of 3 | 5 of 22 | 11 of 22 |
| Dry eye | Eye disorders | 8 of 60 | 3 of 10 | 9 of 21 | 2 of 3 | 6 of 22 | 12 of 22 |
| Diarrhoea | Gastrointestinal disorders | 8 of 60 | 5 of 10 | 8 of 21 | 2 of 3 | 4 of 22 | 11 of 22 |
| Nausea | Gastrointestinal disorders | 7 of 60 | 3 of 10 | 10 of 21 | 0 of 3 | 9 of 22 | 9 of 22 |
| Arthralgia | Musculoskeletal and connective tissue disorders | 8 of 60 | 3 of 10 | 7 of 21 | 2 of 3 | 9 of 22 | 7 of 22 |
| Rash | Skin and subcutaneous tissue disorders | 5 of 60 | 7 of 10 | 6 of 21 | 2 of 3 | 3 of 22 | 9 of 22 |
| Decreased appetite | Metabolism and nutrition disorders | 7 of 60 | 1 of 10 | 8 of 21 | 0 of 3 | 5 of 22 | 7 of 22 |
Serious events with the highest arm-level rate: neutropenia (33.3%), thrombosis in device (33.3%), epistaxis (33.3%), pneumonia (20.0%), thrombocytopenia (10.0%).
The serious adverse-event counts are presented by regimen, with the number of affected participants and the number at risk. In Phase Ib Regimen 1, 7 of 26 participants had a serious adverse event; in Phase Ib Regimen 2, 5 of 10 did; in Phase Ib Regimen 3, 7 of 21 did; and in Phase Ib Regimen 4, 2 of 3 did. The Phase IIa counts are 6 of 22 in Group A and 6 of 22 in Group B. These counts describe the groups as reported and should not be interpreted as a formal comparison.
Group sizes vary, and the regimen groups differ in dose schedule and use of pertuzumab. The record does not report confidence intervals or a statistical model for comparing them. The percentages attached to listed serious-event terms are reported as 33.3% for Neutropenia, Thrombosis in device and Epistaxis; 20.0% for Pneumonia; and 10.0% for Thrombocytopenia and Gastroenteritis. The denominator for these term-specific percentages is not reported in the registry record.
Death is named in the primary outcome, but group-specific death counts are not reported in the registry record. The posted serious-event figures do not establish that an event was caused by a study drug; an adverse event is recorded whether or not it is considered related to the medicinal product.
12. What the Result Does, and Does Not, Mean
The registry record documents a study that evaluated combinations and dosing schedules of T-DM1, paclitaxel and, in some groups, pertuzumab. Its posted safety summaries show that serious adverse events were recorded in each listed regimen group, and it provides counts for other adverse events. Those observations describe what was recorded among participants in the stated groups and follow-up framework. They are not, on their own, estimates of a causal treatment effect.
The record does not provide a single comparative estimate, an uncertainty interval or an inferential test for the safety groups. It also does not supply separate posted counts for Grades 3/4 adverse events or death. The secondary outcomes include response and progression measures, but analyses for those outcomes are not reported in the registry record. Therefore, the posted information cannot establish how the regimens compare in efficacy or provide a precise estimate of any difference.
A lack of a reported comparative result should not be confused with a finding of no difference. It means that the registry record does not provide the analysis needed to assess that question. Similarly, the presence of reported adverse events does not by itself establish that a study drug caused them, because the adverse-event definition includes events whether or not considered related to treatment.
Randomized assignment is listed, but the allocation details and planned comparisons are not reported. The differing group sizes and regimens further limit simple side-by-side interpretation. The observed counts are useful as descriptive safety information; they do not demonstrate that one regimen is safer or more effective than another, and they do not support medical advice for an individual patient.
13. Why This Trial Matters Statistically
Statistically, this record illustrates the distinction between a study’s broad design label and the information needed to interpret a treatment comparison. Randomized parallel assignment is listed, yet the registry record does not describe the allocation procedure, the intended pairwise contrasts or the analysis plan. A label of randomization alone cannot supply those details. The regimens also vary across dose schedules and combinations, so a simple comparison would need to specify exactly which treatment features are being contrasted.
The primary safety outcome is a composite description of several event categories, while the posted group information gives separate participant counts. Those counts are interpretable as descriptive summaries, but they do not constitute a single effect estimate. The absent confidence intervals and statistical comparisons mean that precision and between-group uncertainty cannot be evaluated from the registry record. Different denominators, particularly the small Phase Ib Regimen 4 group, reinforce why raw counts should not be used to rank groups.
The record also demonstrates the importance of distinguishing a study’s planning rationale from later illustrative calculations. The stated planning assumptions describe a hypothetical calculation based on an observed effect, not the original design justification and not observed power. Since the protocol’s sample-size justification is not reported in the registry record, that rationale cannot be reconstructed.
For clinical research readers, the central statistical lesson is that a registry’s outcome definitions, denominators, analysis populations and reported estimates all matter. When the inferential analysis is absent, descriptive safety data remain useful, but their scope must remain descriptive. Transparent reporting of analysis methods and uncertainty would be needed to support stronger comparative conclusions.
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 trial-specific limitations affect interpretation of the posted information. The study combines dose escalation in Phase Ib with Phase IIa groups receiving the maximum tolerated dose identified in Phase Ib. This means the six regimens are not simply identical treatment groups differing in one feature: schedules vary, and pertuzumab is included in some combinations but not others. The registry record does not report the rules used to select the Phase IIa dose or the basis for comparing groups across phases.
Although allocation is listed as randomized, the method of randomization, allocation ratios and group assignment procedures are not reported. The record does not state whether randomization applied to all six groups, how dose escalation related to assignment, or whether treatment groups were intended to be compared statistically. Baseline characteristics by group are also not included in the posted information.
Safety figures have uneven denominators, and Phase Ib Regimen 4 includes 3 participants at risk for serious adverse events. No confidence intervals or adjusted estimates are reported. The figures for other adverse events use different denominators from the serious-event figures in some groups; the reason for that difference is not reported in the registry record. The record also does not provide participant-level event details, event timing, exposure duration, or rates adjusted for time at risk.
The primary outcome names Grades 3/4 adverse events and death, but group-specific counts for those components are not reported. The listed serious-event term percentages have no stated denominator. The registry does not report missing-data handling, analysis populations beyond the safety-population definition, or the statistical plan. It also provides no analyses for the listed secondary outcomes. These gaps prevent assessment of comparative efficacy, precision, multiplicity and the influence of missing observations.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: A Study of Trastuzumab Emtansine, Paclitaxel, and Pertuzumab in Patients With HER2-Positive, Locally Advanced or Metastatic Breast Cancer — NCT00951665.
- Registry record last updated 2016-06-24; status last verified 2016-05.
- Results first posted 2016-06-24.
- 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
The registry describes a completed, randomized, open-label Phase Ib-IIa parallel study of intravenous T-DM1 and paclitaxel, with pertuzumab in some regimens, among participants with HER2-positive locally advanced or metastatic breast cancer. Enrollment was 107. Phase Ib included four dose and combination regimens; Phase IIa included two groups at the maximum tolerated dose identified in Phase Ib.
The primary outcome concerns participants with adverse events, serious adverse events, Grades 3/4 adverse events and death, with observation up to 30 days after the last dose or study discontinuation or termination, whichever is later. Group-level serious and other adverse-event counts are reported, but separate counts for Grades 3/4 events and death are not reported in the registry record. The registry lists response and progression outcomes but provides no outcome analyses. Comparative estimates, confidence intervals, p-values, the detailed analysis plan and the original sample-size justification are not reported in the registry record.