Phase 2 Neoadjuvant Doxorubicin and Cyclophosphamide -> Docetaxel With Lapatinib in Stage II/III Her2Neu+ Breast Cancer: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Phase 2 Neoadjuvant Doxorubicin and Cyclophosphamide -> Docetaxel With Lapatinib in Stage II/III Her2Neu+ Breast Cancer (NCT00404066), a na phase 2 study. The primary outcome is Percentage of Participants With Pathologic Complete Response (pCR).

2. Clinical Question

3. Trial Design

This was a Phase 2, single-group clinical trial in clinical stage II/III HER2-positive breast cancer. The registry record lists enrollment of 21 and a completed status. It gives a start date of 2006-10 and a primary completion date of 2010-12. Allocation is recorded as NA, and masking as none. These design features describe a study without a randomized concurrent control arm; they do not support a direct treatment-versus-control effect estimate.

The neoadjuvant sequence began with doxorubicin and cyclophosphamide every 2 weeks for 4 cycles, with pegfilgrastim or filgrastim growth-factor support, followed by docetaxel and lapatinib for four 21-day cycles and then surgery. The official title also describes 1 year of adjuvant trastuzumab after the neoadjuvant phase and surgery. Dexamethasone and other listed medicines are part of the intervention record, although the available description does not give a complete administration account for all of them.

The primary endpoint was pathologic complete response, assessed at 12 weeks. The description defines it by the absence of invasive disease in excised surgical specimens of the breast and/or axilla. The endpoint population is described as participants who received at least 1 cycle of docetaxel and lapatinib and at least one follow-up evaluation. The record also lists disease-free survival as a secondary outcome, but does not report its result.

The registry record does not report the rationale for the enrollment target, a detailed statistical analysis plan, or a comparison group. Completion status alone does not establish that every planned outcome was fully reported.

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

Reasons for not completing this period:

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.

6. Primary Endpoint

The registry lists the primary outcome as Percentage of Participants With Pathologic Complete Response (pCR), measured over 12 weeks.

The primary endpoint was the percentage of participants with pathologic complete response (pCR), assessed at 12 weeks. The record defines pCR as no evidence of invasive disease in excised surgical specimens of the breast and/or axilla. It specifies that the endpoint applies to participants who received at least 1 cycle of docetaxel and lapatinib and had at least one follow-up evaluation.

General: A pathologic endpoint uses examination of tissue removed at surgery to characterize disease response after neoadjuvant treatment. Unlike an imaging or symptom measure, it is based on the surgical specimen. Expressing the outcome as a percentage describes the proportion of the defined endpoint population meeting the pCR definition. It does not, by itself, describe how precisely that proportion is estimated; an uncertainty interval would help communicate that precision.

The registry record gives the endpoint definition and timeframe, but not the observed percentage, the number meeting the definition, or an uncertainty interval. The endpoint population also has treatment and follow-up eligibility conditions, so the record does not establish from the available information how many enrolled participants contributed to the endpoint result. The result itself is not reported in the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The record describes a Phase 2, single-group study with no masking and no allocation to a concurrent control arm. Its main endpoint is a binary outcome: a participant either meets the pathologic complete response definition or does not. The registry expresses the primary endpoint as a percentage of participants. The actual percentage and its uncertainty are not reported in the registry record.

What does a single-group design estimate?

General: A single-group study can describe outcomes observed among participants receiving a treatment strategy. Without a concurrent control group, it cannot directly estimate a randomized between-group difference. A comparison with an external historical result, if attempted, would require additional assumptions about how comparable the populations, care, and outcome assessment are. The registry record does not report such a comparison.

The single-group design also affects interpretation of the stated aim to determine whether the regimen resulted in an increase in pCR. An increase requires a reference point, such as a comparator or a specified benchmark. Neither a concurrent comparator nor a benchmark is reported in the registry record. The stated purpose is not itself evidence of an observed increase.

How should a binary outcome be read?

General: For a binary endpoint, the observed proportion is the number meeting the endpoint divided by the number assessed in the relevant analysis population. A confidence interval communicates the statistical uncertainty around an estimate; a wider interval indicates less precision than a narrower one. The registry record defines the relevant endpoint population but does not report its size, the observed pCR proportion, or a confidence interval. No such values can be interpreted from the registry record.

The definition requires treatment exposure to docetaxel and lapatinib and at least one follow-up evaluation. These conditions should be kept distinct from the overall enrollment. An endpoint estimate applies to the population used to calculate it, and interpreting that estimate requires knowing who was included and how participants without an assessment were handled. Those details are not reported in the registry record.

What does the planning information mean?

The record describes a planning illustration based on the observed effect, using a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. It also describes the effect to detect as a stated fraction of the observed effect. These assumptions belong to the planning illustration, not to the documented single-group trial design. The registry record does not report the values needed to interpret particular planning scenarios or the trial’s own sample-size justification.

General: A planning sample size is a prospective illustration of how many participants might be needed under specified assumptions. It is not an observed result and is not observed power. In particular, a hypothetical equal-allocation comparison does not turn a single-group trial into a randomized comparison. The planning assumptions cannot substitute for an analysis of the trial’s outcomes.

Why can over-dispersion matter?

General: Over-dispersion occurs when observed variability is greater than a statistical model assumes. If it is ignored, estimated uncertainty can be too small and tests can appear more decisive than warranted. It is relevant in some outcome models, especially when counts vary more than a simple model expects. The registry record does not report a model for over-dispersion or a statistical analysis of the primary endpoint. This general concept should not be read as a claim that over-dispersion occurred in this trial.

What is missing for inferential interpretation?

The registry record lists 0 analyses. It does not report a p-value, confidence interval, model specification, adjustment strategy, or an analysis population count for the primary endpoint. A p-value, when reported, addresses compatibility of data with a specified statistical model and null hypothesis; it does not quantify the size or clinical importance of an effect. A confidence interval would provide a range of estimates compatible with the data and model, while still depending on assumptions and the quality of the underlying measurements.

Because the primary endpoint result and inferential analysis are not reported, no recalculated estimate can be interpreted. There is no posted summary result from which to assess precision or compare an unadjusted calculation with a sponsor analysis. The registry record does not report a sponsor analysis for this endpoint.

10. Exact Estimates for Each Arm

No two-arm comparison is shown for this trial, but each arm's result can still be summarized with exact interval estimates computed from the posted counts. The Clopper-Pearson interval is exact and conservative; the Wilson interval is a common closer-to-nominal alternative; the Bayesian credible interval uses a uniform Beta(1, 1) prior. For small groups the three can differ noticeably.

R code and output

arm    <- c("Neoadjuvant Chemotherapy")
n      <- c(18)
events <- c(7)
for (i in seq_along(n)) {
  ci <- binom.test(events[i], n[i])$conf.int          # Clopper-Pearson exact interval
  cr <- qbeta(c(0.025, 0.975), 1 + events[i], 1 + n[i] - events[i])   # Bayesian, uniform Beta(1,1) prior
  wi <- (function(x, n) { p <- x / n; z <- qnorm(0.975); d <- 1 + z^2 / n
    c((p + z^2 / (2 * n) - z * sqrt(p * (1 - p) / n + z^2 / (4 * n^2))) / d, (p + z^2 / (2 * n) + z * sqrt(p * (1 - p) / n + z^2 / (4 * n^2))) / d) })(events[i], n[i])
  cat(sprintf("ARM|%s|%d|%d|%.1f|%.1f|%.1f|%.1f|%.1f|%.1f|%.1f\n", arm[i], n[i], events[i], 100 * events[i] / n[i],
              100 * ci[1], 100 * ci[2], 100 * wi[1], 100 * wi[2], 100 * cr[1], 100 * cr[2]))
}

ARM  Neoadjuvant Chemotherapy  18  7  38.9  17.3  64.3  20.3  61.4  20.3  61.6

11. Multiplicity, Missing Data and Analysis Populations

The registry record identifies pCR as the primary outcome and disease-free survival as a secondary outcome. It lists 2 outcome measures and 0 analyses. It does not report results for either endpoint, nor does it provide a statistical plan describing how multiple outcomes or repeated tests were handled.

General: When several outcomes or hypotheses are examined, the chance of at least one apparently noteworthy finding can increase if each is interpreted independently. A prespecified hierarchy, adjustment procedure, or clear distinction between primary and exploratory analyses can help readers understand the scope of testing. No such approach is reported in the registry record, so it is not possible to assess how multiplicity was addressed.

Missing outcome information is also not described. The pCR definition applies to participants who received at least 1 cycle of docetaxel and lapatinib and at least one follow-up evaluation, but the record does not report how many met those conditions, whether any endpoint assessments were missing, or how missing data were handled. It does not report whether the analysis followed an intention-to-treat principle or another analysis-population definition.

These omissions limit interpretation independently of the treatment sequence. Without the outcome population, missing-data handling, and analysis plan, the completeness and potential selection of the reported endpoint cannot be assessed. The registry record does not report these details.

12. Safety Results

The registry reports serious adverse events as affected participants divided by participants at risk.

Deaths

Other (non-serious) adverse events

Participants with at least one non-serious event at or above the registry's 0% reporting threshold.

Most frequent non-serious adverse event terms

The registry lists 0 participants affected in the serious adverse-event category among 21 at risk. It lists 21 participants affected in the other adverse-event category among 21 at risk, and 2 deaths. These entries are descriptive counts in the registry record; they do not give event-level detail or an attribution to a particular medicine.

The record does not list serious adverse-event terms, explain the circumstances or timing of the deaths, or state whether any event was considered related to treatment. It also does not provide a concurrent control group for comparison. The adverse-event figures therefore do not establish causation, comparative safety, or the severity and duration of individual events.

General: Safety counts need to be read with their categories, observation periods, and analysis populations in mind. A count of affected participants is not necessarily the same as a count of all events, since one participant can experience more than one event. The registry record does not provide enough detail to determine event counts or characterize individual clinical courses.

13. What the Result Does, and Does Not, Mean

This record describes a Phase 2 investigation of a neoadjuvant treatment sequence for clinical stage II/III HER2-positive breast cancer. The regimen included doxorubicin and cyclophosphamide followed by docetaxel with lapatinib and surgery; the official title also describes adjuvant trastuzumab for 1 year. The primary outcome was defined as pCR in surgical specimens at 12 weeks, for participants meeting the stated treatment and follow-up conditions.

The record does not report the pCR result, its uncertainty, or a statistical analysis. It also does not report the disease-free survival result. Accordingly, the registry information cannot show the magnitude or precision of the primary outcome in this trial. The study purpose, as recorded, is not a substitute for an observed result.

The single-group design has no concurrent control arm. Any observed outcome in such a design would describe participants in the study, not establish a difference relative to an alternative regimen. The record also does not provide the analysis population size or details about missing outcome data, which are important for understanding how the endpoint estimate would apply.

The listed safety counts offer limited descriptive information: 0 affected in the serious adverse-event category among 21 at risk, 21 affected in the other adverse-event category among 21 at risk, and 2 deaths. The registry record does not provide event terms or enough detail to attribute events to treatment or assess comparative safety.

Thus, the available record establishes the trial design, treatment sequence, endpoint definition, and selected adverse-event counts. It does not establish whether the regimen changed pCR, how precisely an outcome was estimated, or whether outcomes differed from those under another treatment strategy.

14. Why This Trial Matters Statistically

This trial illustrates why a clearly defined endpoint and a reported result are both necessary for statistical interpretation. The registry record specifies pCR as the primary outcome, describes the surgical specimen criteria, and states a 12 weeks timeframe. Those details clarify what was intended to be measured. But the observed percentage and its uncertainty are not reported, so the endpoint definition alone cannot answer the study question.

The single-group design is also important. It can describe outcomes in the treated study population, but does not provide a concurrent control for estimating a comparative effect. This distinction matters when a study’s purpose is phrased in terms of an increase: a comparative claim needs a reference that is defined and analyzed. The registry record does not report such a comparison.

The record also distinguishes enrollment from the endpoint population. The pCR definition includes treatment exposure and follow-up conditions, while the size of that endpoint population is not reported. Without the analysis population and missing-data details, readers cannot assess how complete or representative the endpoint assessment was.

Finally, the planning illustration uses assumptions for a hypothetical two-arm comparison, whereas the trial is recorded as single group. Planning calculations can illustrate sample-size consequences of assumptions, but cannot supply evidence of an observed treatment effect. This trial is therefore a useful example of separating design, endpoint definition, planning assumptions, and results: they answer different statistical questions.

15. 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 registry record does not report the primary pCR result, its precision, or an inferential analysis. It also does not report the disease-free survival result. As a result, the main efficacy question cannot be answered from the recorded outcome information.

The study is identified as single group, with allocation recorded as NA and no masking. There is no concurrent comparator, so the design does not provide a randomized estimate of a difference between treatment strategies. The record does not describe a benchmark or external comparison used to evaluate the stated aim of an increase in pCR.

The pCR endpoint applies to participants who received at least 1 cycle of docetaxel and lapatinib and had at least one follow-up evaluation. The record does not state how many participants met these conditions, how many had missing assessments, or how those assessments were handled. This prevents evaluation of the endpoint analysis population and the potential influence of missing data.

The adverse-event information is limited to category counts and deaths. Event terms, timing, severity details beyond the category, and attribution are not reported. There is no concurrent safety comparator. The registry record also does not report a detailed statistical analysis plan, multiplicity procedures, or the rationale for the enrollment target. These limitations are specific to what is recorded and should not be treated as proof that unreported procedures or analyses did not occur.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Phase 2 Neoadjuvant Doxorubicin and Cyclophosphamide -> Docetaxel With Lapatinib in Stage II/III Her2Neu+ Breast Cancer — NCT00404066.
• Registry record last updated 2017-12-22; status last verified 2017-11.
• Results first posted 2017-12-22.
• 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.

19. Record Summary

The registry record describes a completed Phase 2, single-group study in clinical stage II/III HER2-positive breast cancer, with enrollment of 21. The treatment sequence included doxorubicin and cyclophosphamide followed by docetaxel with lapatinib and surgery; the official title also describes adjuvant trastuzumab for 1 year.

The primary endpoint was pCR at 12 weeks, defined by no invasive disease in excised breast and/or axillary specimens for participants meeting the specified treatment and follow-up conditions. Disease-free survival was listed as a secondary outcome. The record lists 0 analyses and does not report either outcome result.

Safety entries include 0 affected in the serious adverse-event category among 21 at risk, 21 affected in the other category among 21 at risk, and 2 deaths. Details about event terms, attribution, and the circumstances of deaths are not reported in the registry record.