Phase II Neoadjuvant in Inflammatory Breast Cancer: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Phase II Neoadjuvant in Inflammatory Breast Cancer (NCT00756470), a na phase 2 study. The primary outcome is Rate of Pathologic Complete Response (pCR) Following Neoadjuvant Chemotherapy.

2. Clinical Question

3. Trial Design

This was a Phase II study listed as a single-group trial. Enrollment was 15, and the registry status is terminated. The record gives a start date of 2008-10 and a primary completion date of 2013-10. It does not report a randomized allocation, a masking procedure, or a concurrent control arm: allocation is listed as not applicable, masking as none, and the model as single group. The study consequently describes an intervention sequence without a direct between-group comparison.

The intervention combined lapatinib with chemotherapy in a neoadjuvant setting. The arm description specifies lapatinib alone at 1,000 mg orally once daily during a 2-week run-in. It then describes four cycles of lapatinib and paclitaxel followed by four cycles of lapatinib plus 5-fluorouracil, cyclophosphamide, and epirubicin (FEC75). Each cycle is described as 21 days. The stated primary endpoint was assessed at surgery after the neoadjuvant chemotherapy, approximately 26 weeks following its start.

The primary endpoint is a participant-level binary outcome: whether or not pCR was observed. The record defines the analysis population as all participants who received any treatment, described as an intent-to-treat population analysis. It also lists a secondary outcome concerning pCR after completion of all protocol-specified therapy and surgery in the surgical population. The registry record does not report numerical results for these outcomes, nor does it describe the statistical analysis used to estimate them.

Termination is a registry status, not an explanation of why the study ended. The reason for termination is not reported in the registry record. The record also does not report a sample-size justification, planned enrollment target, or whether enrollment reached a prespecified target. These omissions limit interpretation of the study's planning and conduct, apart from the recorded enrollment of 15.

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: Study terminated early due to slow enrollment and review of futility.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: With an intent-to-treat population analysis, all participants who received any treatment were included in the analyses.

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 Rate of Pathologic Complete Response (pCR) Following Neoadjuvant Chemotherapy, measured over Assessed at time of surgery following completion neoadjuvant chemotherapy (approximately 26 weeks).

The primary endpoint is the rate of pathologic complete response following neoadjuvant chemotherapy. The registry defines pCR as having no residual invasive malignant cells in either the breast or axillary lymph nodes at surgery after all protocol-specified neoadjuvant chemotherapy. Assessment was planned at surgery, approximately 26 weeks after the start of neoadjuvant chemotherapy. The endpoint is expressed as a percentage of participants.

As a binary endpoint, each participant is classified according to whether the pCR definition was met. A rate describes the share of an analyzed group meeting that definition; it does not by itself describe the timing of response, changes in tumor size, or outcomes beyond the specified assessment. The endpoint is clinically interpretable because it records residual invasive disease at surgery, but its meaning depends on the definition, assessment timing, and population included in the analysis.

The registry specifies an intent-to-treat population analysis that includes all participants who received any treatment. It does not report the number meeting the pCR definition, the denominator used for the posted result, or an estimated pCR rate. The numerical primary endpoint result is not reported in the registry record, so the endpoint's observed value and its precision cannot be assessed from the posted information.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

What does a binary endpoint estimate?

In general, a binary endpoint places each participant into one of two categories, such as meeting or not meeting a prespecified response definition. A rate is the proportion of an analyzed group in the category of interest, often presented as a percentage. For this trial, the category of interest is pCR, defined by the absence of residual invasive disease in the breast and axillary lymph nodes at surgery after neoadjuvant chemotherapy.

The result depends on both the numerator and denominator: how many participants met the definition and which participants were included in the analysis. The registry describes an intent-to-treat population analysis including all participants who received any treatment. It does not report the number meeting the pCR definition or a numerical rate. It is therefore not possible to interpret the magnitude of the primary endpoint estimate from the posted results.

What would a confidence interval communicate?

In general, a confidence interval expresses uncertainty around an estimated effect or rate. A narrower interval indicates greater precision under the method used; a wider interval indicates less precision. For a participant-level binary outcome, the interval depends on the observed data and the estimation method. The registry record does not report a confidence interval for the primary endpoint, or the numerical pCR rate needed to understand one. The degree of statistical precision is therefore not reported in the registry record.

A confidence interval does not correct for limitations in the study design, and it does not establish that a result applies beyond the studied group. In a single-group study, an interval around a pCR rate would describe uncertainty in that group's rate under the analysis assumptions. It would not provide a randomized comparison with another treatment or a control condition.

What can a single-group design show?

In general, a single-group study can describe outcomes among participants receiving the study regimen. It lacks a concurrent comparator, so it cannot directly estimate a between-group treatment contrast. Differences between participants and other groups, changes in care over time, and other influences cannot be addressed through a randomized comparison when no comparator group is included. The record lists the model as single group and allocation as not applicable; no randomized comparison is reported.

The primary endpoint's definition and assessment time are specified, but the registry record does not report the statistical method used to estimate the pCR rate. It also does not report whether an inferential test was planned or performed. General statistical interpretation must therefore distinguish the design information that is posted from analysis details that are not reported in the registry record.

How should safety percentages be read?

In general, an adverse-event percentage describes the share of a stated population affected by a specified event or event category. The registry lists 15 participants at risk for other adverse events and 15 affected, and 15 at risk for serious adverse events with 7 affected. It also lists percentages for several serious adverse-event terms. The record does not state the event-counting rules for repeated events, provide event-level timing, or indicate whether a participant could contribute to more than one term. These percentages should therefore be read as posted safety summaries, not as mutually exclusive categories or as comparative treatment effects.

Over-dispersion is a general statistical concern when the variability in count data is greater than a model assumes. A model that ignores extra variability can produce uncertainty estimates that are too small. This issue is relevant in general to count outcomes and repeated events, but the registry record does not report a count-model analysis for this study. It does not state that over-dispersion was assessed or that such a model was used.

What do planning illustrations mean?

In general, sample-size calculations describe how many participants might be needed under stated assumptions to detect a specified effect with a chosen statistical procedure. The registry's planning assumptions describe a two-sided significance level of 0.05, equal allocation between two arms, a normal approximation, and effects framed as fractions of the observed effect. These are planning illustrations, not the design of the reported single-group trial. They are not observed power and do not demonstrate the probability that the study detected an effect after it was conducted.

The registry record does not report its own sample-size justification or statistical analysis plan. It also does not report the numerical observed primary effect needed to interpret planning illustrations tied to fractions of that effect. The listed assumptions should not be mistaken for evidence that the actual study had two randomized arms, or that a prespecified power target was met.

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 Lapatinib Plus Chemotherapy")
n      <- c(15)
events <- c(1)
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 Lapatinib Plus Chemotherapy  15  1  6.7  0.2  31.9  1.2  29.8  1.6  30.2

11. Multiplicity, Missing Data and Analysis Populations

The registry lists a primary pCR outcome and a secondary pCR outcome defined for the surgical population. It does not report a statistical analysis plan describing how multiple endpoints or analyses were to be handled. In general, when several hypotheses are tested, the chance of at least one apparently positive result can increase unless the analysis addresses multiplicity. The record does not say whether any adjustment or hierarchical testing strategy was planned or used. No multiplicity method is reported in the registry record.

The record describes the primary analysis population as all participants who received any treatment. It does not explain how participants without a surgery assessment, incomplete treatment, or missing endpoint information were handled. The number with missing primary outcome data, if any, is not reported in the registry record. The posted information also does not specify whether missing data were imputed, treated as non-response, excluded from an analysis, or handled using another method.

The secondary outcome is specified for the surgical population, which is narrower in wording than the primary intent-to-treat population. The record does not report the size of that population or how it relates to the participants who received treatment. Without those details and numerical outcome results, it is not possible to assess the impact of missing observations or differences between analysis populations.

The record reports zero analyses and gives no numerical outcome result. It does not report an interim analysis plan, stopping rule, or adjustment for interim looks. These details are not reported in the registry record and should not be inferred from the trial's terminated status.

12. Safety Results

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

Other (non-serious) adverse events

Participants with at least one non-serious event at or above the registry's 5% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: diarrhea (46.7%), neutropenia (20.0%), skin rash (20.0%), fatigue (20.0%), neutropenic fever (6.7%).

The registry lists 15 participants at risk for serious adverse events, with 7 affected. For other adverse events, it lists 15 at risk and 15 affected. These figures describe participant counts in the intervention group; the record does not provide a control group for comparison. The serious adverse-event terms with listed percentages are diarrhea at 46.7%, neutropenia at 20.0%, skin rash at 20.0%, fatigue at 20.0%, and neutropenic fever at 6.7%.

These summaries should not be read as the number of total episodes. The record does not specify whether repeated events in one participant were counted once or multiple times for each term, nor does it provide onset, duration, severity grading, or attribution details for the listed terms. The listed percentages also do not establish that the categories are mutually exclusive; one participant may potentially be represented under more than one term, but overlap is not reported in the registry record.

The safety figures describe what is posted for this study group. Without a comparator and fuller event details, they do not support a comparative safety estimate. The record does not report deaths in the adverse-event summary.

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

The registry record documents a Phase II, single-group study of neoadjuvant lapatinib combined with chemotherapy in women with inflammatory breast cancer whose tumors overexpressed ErbB2 (HER2/neu). It specifies pCR at surgery as the primary endpoint and defines the absence of residual invasive disease in the breast and axillary lymph nodes as the response criterion. It also provides enrollment and selected safety summaries.

The central primary outcome result is not reported in the registry record. There is no posted pCR count or rate, and no confidence interval or statistical test result for that endpoint. The information therefore cannot establish the observed pCR frequency or how precisely it was estimated. The secondary pCR outcome is also listed without a numerical result.

Even if a numerical response rate were available, a single-group design would describe the outcome in the participants receiving the regimen; it would not quantify a randomized difference from another approach. The posted record contains no concurrent control group. The safety figures likewise describe the study group and cannot be interpreted as comparative estimates.

The safety summary reports serious adverse events affecting 7 of 15 participants at risk and other adverse events affecting 15 of 15 at risk, along with percentages for selected serious adverse-event terms. The record does not provide event-level detail needed to understand timing, repeated events, grading, or overlap between terms. These data are descriptive and should be read within those limits.

Overall, the record supports statements about the study's design, endpoint definition, enrollment, and listed safety figures. It does not support a conclusion about the magnitude or precision of the primary response result, nor a comparison of treatment effects. The reason for termination and the study's statistical analysis plan are not reported in the registry record.

14. Why This Trial Matters Statistically

This study is statistically notable because its principal outcome is defined clearly as a binary response at surgery, yet the registry record does not report the numerical result. The distinction between a well-defined endpoint and a reported estimate matters: a definition explains what was measured, while the event count and denominator are needed to understand the observed rate. Without that result, the endpoint cannot be quantitatively interpreted.

The design also shapes the questions that can be answered. A single-group Phase II study can describe outcomes in the enrolled group, but it does not provide a randomized contrast. This is important when readers see a treatment sequence and an outcome label: the design itself does not isolate the effect of the regimen from other influences on outcomes. The absence of a reported comparator is a design limitation, not a statistical adjustment that can be resolved from the posted information.

The record distinguishes an intent-to-treat population for the primary endpoint from a surgical population for the secondary outcome. That distinction can affect denominators and interpretation. However, the registry does not report population counts, missing outcome data, or numerical results for either endpoint, so the impact cannot be evaluated.

Finally, planning illustrations and observed results answer different questions. The recorded planning assumptions do not describe a randomized two-arm trial design, and sample-size illustrations are not observed power. Separating planning assumptions, design features, and outcome evidence helps prevent hypothetical calculations from being mistaken for findings from the trial.

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 numerical primary pCR result, its denominator, or a measure of uncertainty. It also does not report a numerical result for the listed secondary pCR outcome. This prevents assessment of the observed response frequency and the precision of either endpoint estimate.

The study is single group, with allocation recorded as not applicable and masking as none. No concurrent comparator is reported, limiting direct comparative interpretation. Enrollment was 15, but the record does not report further participant characteristics or the size of the surgical population used for the secondary outcome.

The registry describes an intent-to-treat analysis including all participants who received any treatment, but does not describe the handling of missing endpoint data, incomplete treatment, or participants without surgery assessment. The number of missing outcomes is not reported in the registry record. The statistical analysis method, multiplicity approach, interim analyses, sample-size justification, and analysis plan are also not reported.

Safety information is limited to participant counts and selected serious adverse-event percentages. The record does not provide event-level timing, severity grades, repeated-event handling, or details about overlap among terms. The reason for the terminated status is not reported in the registry record, so its implications for enrollment, follow-up, or outcome reporting cannot be determined.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Phase II Neoadjuvant in Inflammatory Breast Cancer — NCT00756470.
• Registry record last updated 2014-11-17; status last verified 2014-11.
• Results first posted 2014-11-05.
• 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

This registry record describes a Phase II, single-group study of neoadjuvant lapatinib with paclitaxel and FEC75 chemotherapy in women with inflammatory breast cancer whose tumors overexpressed ErbB2 (HER2/neu). Enrollment was 15, and the record lists the trial status as terminated. The primary endpoint was pCR at surgery after neoadjuvant chemotherapy, approximately 26 weeks after treatment began.

The record defines pCR and describes an intent-to-treat primary analysis population, but the numerical primary result and its precision are not reported in the registry record. A secondary pCR outcome is listed for the surgical population without a numerical result. Safety figures include serious adverse events affecting 7 participants among 15 at risk and other adverse events affecting 15 among 15 at risk. No concurrent comparator is reported. The reason for termination and the statistical analysis plan are not reported in the registry record.