Doxorubicin and Cyclophosphamide Followed by Paclitaxel, Trastuzumab, and Lapatinib in Treating Patients With HER2/Neu-Overexpressed Breast Cancer: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Doxorubicin and Cyclophosphamide Followed by Paclitaxel, Trastuzumab, and Lapatinib in Treating Patients With HER2/Neu-Overexpressed Breast Cancer (NCT00482391), a na phase 2 study. The primary outcome is Number of Patients Who Completed All Planned Therapy.

2. Clinical Question

The clinical question is therefore about whether participants in this study completed the planned treatment sequence, not whether the regimen outperformed another treatment. The study title and brief summary frame the work around a treatment for HER2/neu-positive breast cancer; its official title specifically identifies feasibility as the focus. The record lists 95 as the enrollment figure, but does not report how many participants completed all planned therapy.

The primary outcome description refers to patients with HER-2/neu-overexpressed or amplified breast cancer and defines the outcome as the number completing the dose-dense adjuvant or neoadjuvant chemotherapy regimen. The registry record does not report separate outcome results for adjuvant and neoadjuvant use, or describe how participants were classified for those settings. It also does not report a comparator, so the primary question cannot be interpreted as a treatment-effect estimate against a control group.

3. Trial Design

The registry record identifies this as a phase II, single-group study. Allocation is listed as NA and masking as none. These entries describe a study without a listed randomized allocation or masking procedure; the record does not describe a control arm for a like-for-like comparison. The study title and official title identify a treatment sequence for HER2/neu-overexpressed or amplified breast cancer, with feasibility as the stated focus.

The regimen description begins with doxorubicin 60 mg/m2 and cyclophosphamide 600 mg/m2 every 14 days for 4 cycles, with pegfilgrastim, followed by weekly paclitaxel 80 mg/m2 for 12 cycles with trastuzumab and lapatinib. Pegfilgrastim 6mg is described as given subcutaneously on day 2 of each AC cycle. The regimen text also says filgrastim may be used in lieu of peg, but does not complete that wording in the registry description. The record lists trastuzumab, cyclophosphamide, doxorubicin hydrochloride, lapatinib ditosylate, paclitaxel, and laboratory biomarker analysis among the interventions.

The registry lists enrollment as 95, a study start of 2007-03, primary completion of 2011-07, and status as completed. These record entries do not establish how many participants contributed to the primary outcome or whether every participant received every planned treatment component. The primary outcome timeframe is 2 years. The registry record does not report the timing of outcome collection for each participant or explain how that timeframe was applied.

The primary outcome is the number of patients who completed all planned therapy. The listed secondary outcome is the number of patients evaluated for toxicity. The record reports 2 outcome measures and 0 analyses. It does not report a statistical analysis plan, sample-size justification, prespecified interim analyses, or detailed eligibility criteria in the registry record for this trial.

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 Number of Patients Who Completed All Planned Therapy, measured over 2 years.

The primary endpoint is titled “Number of Patients Who Completed All Planned Therapy.” It is a count of participants, with a stated timeframe of 2 years. The description defines completion in relation to the planned dose-dense adjuvant or neoadjuvant chemotherapy regimen for patients with HER-2/neu-overexpressed or amplified breast cancer. The endpoint therefore records whether participants reached the end of the planned treatment sequence, rather than measuring a time-to-event outcome or a change in a continuous measurement.

In a feasibility study, treatment completion can describe whether participants were able to proceed through the planned regimen. It can complement safety monitoring by giving a direct account of completion, although it does not by itself explain why a participant did or did not complete treatment. General statistical interpretation: a count is easiest to interpret alongside its denominator and a clear definition of completion. The registry record lists enrollment as 95 but does not report the primary endpoint count, the analysis denominator, or rules for handling partial treatment, withdrawal, or missing outcome information.

The endpoint can describe treatment delivery in this study, but cannot alone establish comparative benefit or distinguish among reasons for non-completion. The record does not report a comparison group or a separate endpoint result for adjuvant and neoadjuvant treatment. The endpoint result itself is not reported in the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry record identifies a phase II, single-group study with allocation listed as NA and masking listed as none. These design details shape which statistical questions can be answered. A single-group study can describe outcomes among participants who received the study regimen, but it does not provide a concurrent randomized control group for estimating a treatment contrast. The record does not describe a comparator arm or a randomized allocation process. It is therefore not appropriate to interpret the listed outcomes as evidence of a difference versus another treatment.

What does the primary outcome measure?

The primary outcome is a count: the number of patients who completed all planned therapy. Its stated timeframe is 2 years. Counts are direct summaries of how many participants meet an outcome definition, but interpretation depends on knowing both the definition and the denominator. Here, the outcome description refers to completing the planned dose-dense adjuvant or neoadjuvant chemotherapy regimen. The registry record does not report the number meeting that definition or the denominator used for the endpoint analysis. Although the enrollment entry is 95, it cannot be assumed from the record alone that this was also the analysis population for the primary outcome.

General statistical explanation: a proportion can often make a count easier to interpret across studies with different group sizes, but it requires a specified numerator and denominator. No primary endpoint count or analysis denominator is reported, so a completion proportion cannot be interpreted from this registry record. No calculation should be substituted for a missing endpoint result.

What does a single-group design imply?

In a comparative trial, a treatment effect is typically expressed as a contrast between groups. In this study record, the design is single-group, and the allocation field is NA. There is no listed control group against which the completion outcome or safety summary can be contrasted. General statistical explanation: random allocation, when used, helps balance measured and unmeasured prognostic factors between groups on average. Without such a comparison, observed outcomes can describe the study group, but do not isolate the effect of the regimen from other possible influences.

The record's phase II designation does not establish a particular statistical plan. Phase labels are not a substitute for reported methods. The registry record does not report a sample-size justification, a target completion threshold, an interim monitoring plan, or the criteria used to assess feasibility. It is not possible to infer any of these elements from the phase designation or the enrollment entry.

What statistical results are available?

The record lists 0 analyses and does not provide a numerical primary endpoint result, confidence interval, or hypothesis test. It also does not report a model, adjustment variables, or an approach for estimating uncertainty around the completion count. General statistical explanation: an estimate describes the observed result, while an uncertainty interval indicates how imprecise that estimate may be under specified assumptions. A p-value addresses a particular statistical hypothesis under a model; it is not a measure of the size or clinical importance of an effect. None of these inferential quantities is reported for the primary outcome.

The registry lists 2 outcome measures: the primary completion outcome and the secondary outcome “Number of Patients Who Were Evaluated for Toxicity.” A measure's listing does not indicate that its result is available. The record does not report a result for the toxicity-evaluation outcome, nor does it give analysis details for either outcome.

How should safety counts be read?

The adverse-event summary gives the number at risk and the number affected for serious and other adverse events in the listed group. Those are descriptive counts in the registry record. They are not comparative estimates, and the record does not describe an adjusted analysis. General statistical explanation: adverse-event summaries may count participants with at least one event, individual event occurrences, or events grouped by a coding convention; the exact meaning depends on the registry's definitions. The available information does not specify those details. It also does not give a detailed timeframe or explain whether participants could appear in more than one event category.

The record lists several serious-event terms with percentages. Those percentages should be read as the registry's reported entries, without converting them to counts or combining them. The record does not specify the denominator associated with each percentage or explain the method used to produce it. The serious-event figure and the term-specific percentages may not represent the same summary unit, so they should not be treated as interchangeable.

What cannot be inferred?

No missing statistical method can be reconstructed from the regimen description, the study status, or the reported safety counts. The registry record does not report how missing outcome data were handled, which participants were included in each analysis, whether endpoint adjudication was used, or whether any analyses were adjusted. General statistical explanation: missing-data rules and analysis-population definitions matter because they can affect which participants contribute to an estimate and how that estimate should be interpreted. Without those details and an outcome result, the primary endpoint's magnitude and precision remain unknown.

The sample-size planning assumptions described for other analyses are not a substitute for trial-specific methods. Any sample-size illustration based on an observed effect is a planning exercise, not observed power and not evidence that this trial achieved a particular level of precision. The registry record does not report the trial's own statistical rationale for its enrollment. Consequently, the most defensible statistical reading is descriptive: the registry identifies the study design, intended endpoint, treatment sequence, and selected safety counts, while leaving the primary outcome result and its analysis unreported.

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("AC, PACLITAXEL , TRASTUZUMAB & LAPATINIB")
n      <- c(92)
events <- c(45)
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  AC, PACLITAXEL , TRASTUZUMAB & LAPATINIB  92  45  48.9  38.3  59.6  38.9  59.0  38.9  59.0

11. Multiplicity, Missing Data and Analysis Populations

The registry record lists a primary outcome and a secondary outcome, but does not report a statistical analysis plan, hypothesis tests, or endpoint-specific results. It lists 0 analyses. The record does not describe whether any formal testing was planned or how the study would address multiplicity if several outcomes or comparisons were tested. It is therefore not possible to determine whether multiplicity adjustments were planned or needed. No p-value or multiplicity-adjusted conclusion is reported for the primary endpoint.

The registry record does not report how missing outcome data were handled. It does not say whether participants without a recorded completion status were excluded, counted as not completing, or addressed through another method. It also does not give the primary endpoint analysis denominator. The enrollment entry of 95 should not be treated as a confirmed denominator for the completion outcome without an explicit statement in the record.

The record does not define an analysis population, such as all enrolled participants or participants who started treatment, and does not report which participants contributed to each outcome. It also does not explain whether outcome assessment was based on all participants or a subset. These omissions matter because the population included in an analysis and the handling of missing observations can change the interpretation of a count. No analysis population or missing-data method should be inferred from the completed study status or the adverse-event summaries.

General statistical explanation: multiplicity concerns arise when multiple statistical questions are assessed, because repeated testing can increase the chance of a misleading finding. Missing-data methods require assumptions about why information is absent and how that absence relates to outcomes. The registry record does not provide the information needed to evaluate either issue for this study.

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: dyspnea (shortness of breath) (6.3%), fever (4.2%), diarrhea (3.2%), hemoglobin (2.1%), hypotension (2.1%).

The registry adverse-event summary lists 23 of 95 at risk as affected for serious adverse events and 94 of 95 at risk as affected for other adverse events in the study group. These are descriptive entries, not a comparison with another treatment group. Deaths are listed as null, so a death count is not reported in the registry record.

The record lists the following serious-event terms and percentages: dyspnea (shortness of breath), 6.3%; fever, 4.2%; diarrhea, 3.2%; hemoglobin, 2.1%; hypotension, 2.1%; and “Inf norm ANC/gr1/2 neut-Cellulitis(skin),” 2.1%. These are registry labels and reported percentages. The record does not specify the denominator for each term, the event definitions, the reporting window, or whether the percentages refer to participants or events. The terms should therefore be read as listed, not reinterpreted as precise participant-level risks.

General statistical explanation: adverse-event categories can overlap, because a participant may experience more than one kind of event. As a result, term-specific percentages should not be added to produce an overall rate. A registry summary also does not, by itself, establish whether an event was caused by treatment. The record does not provide an attribution analysis or a comparator-based safety estimate.

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

The record identifies a feasibility-focused phase II study of a treatment sequence for HER2/neu-overexpressed or amplified breast cancer. Its primary outcome asks how many patients completed all planned therapy within 2 years. That is a relevant treatment-delivery question: it concerns completion of the regimen as planned, rather than a direct measure of a between-group treatment effect. However, the primary endpoint result is not reported in the registry record, so the extent of completion cannot be assessed from the information recorded.

The study's single-group design also limits the scope of any interpretation. The record does not describe a control arm or randomized comparison. Even if a completion count were available, it would describe outcomes in the study group and would not establish how outcomes would compare under a different regimen. No comparative estimate, confidence interval, or statistical test for the primary outcome is reported.

The adverse-event summary records affected counts for serious and other adverse events, along with selected serious-event terms and percentages. These entries describe what the registry reports, but they do not answer the primary completion question. The record does not report event definitions, detailed denominators for the term-specific percentages, or an analysis attributing events to treatment. The safety figures should not be interpreted as a causal comparison or a complete account of the regimen's risks.

General statistical explanation: a study result is most informative when the outcome definition, analysis population, denominator, estimate, and uncertainty are reported together. The registry record does not provide these elements for the primary outcome. The listed enrollment, completed status, regimen details, and safety counts cannot fill that gap or be used to infer an unreported completion result.

Thus, the record supports a description of what the investigators set out to assess and how the regimen was organized. It does not establish the observed completion frequency, the precision of that frequency, or a treatment effect relative to a comparator. It also does not establish whether the regimen should be used in any individual situation.

14. Why This Trial Matters Statistically

This study illustrates why a feasibility question and a treatment-effect question should be kept distinct. The registry's primary outcome is completion of planned therapy, a measure of whether participants reached the end of the intended regimen. That can be an important aspect of evaluating a complex treatment sequence. It is not, by itself, a measure of comparative effectiveness, and the single-group design does not include a listed control group for estimating a treatment contrast.

The record also shows why an endpoint's name and timeframe are not enough to interpret a result. The primary outcome is defined as a participant count over 2 years, but the registry does not report the count or the analysis denominator. Without those, readers cannot determine the observed completion frequency or its precision. The enrollment entry does not replace an outcome result.

General statistical explanation: careful reporting links each endpoint to its definition, analysis population, denominator, estimate, and uncertainty. It also explains how missing information and multiple analyses were handled. Those details help readers distinguish a planned measure from an observed result and a descriptive summary from an inferential claim. Here, the registry lists 2 outcome measures but provides no analysis results and no reported statistical plan.

The safety summary offers another statistical lesson. Aggregate affected counts and selected term-specific percentages can provide descriptive information, but interpretation depends on definitions, denominators, time windows, and whether categories overlap. The registry record does not report enough detail to resolve those issues or to make a comparison against another regimen.

The study is therefore statistically informative as a record of a single-group feasibility question, a specified treatment sequence, and selected adverse-event summaries. Its limitations are also instructive: a completed status does not substitute for an endpoint result, and descriptive safety entries do not establish comparative effects or causation. Clear reporting of the planned analysis and observed endpoint would be needed to evaluate the primary feasibility outcome quantitatively.

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 primary limitation for interpreting this trial is that the registry record does not report the primary outcome count, despite identifying completion of all planned therapy as the primary endpoint. It also does not report the endpoint analysis denominator. The enrollment entry of 95 cannot be assumed to be the number included in that analysis. Consequently, the primary outcome's observed magnitude and precision cannot be assessed.

The single-group design, with allocation listed as NA, provides no described comparator for evaluating outcomes against another treatment. The record does not describe randomized allocation or masking. It also does not report a statistical analysis plan, sample-size justification, interim analyses, target completion criterion, or adjustment methods. The phase II designation and feasibility focus do not supply those missing details.

The registry record does not explain how participants were handled if they did not complete treatment, had incomplete outcome information, or were evaluated for toxicity only. It does not define an analysis population or specify missing-data methods. The primary outcome description refers to adjuvant or neoadjuvant therapy, but the record does not report separate results for those settings or explain their analysis.

Safety interpretation is also limited by the absence of detailed definitions, event timing, term-specific denominators, and an explanation of how percentages were calculated. The death entry is null, so a death count is not reported. The record does not describe event attribution or provide a comparator-based safety analysis. These limitations mean the listed adverse-event summaries should be treated as registry descriptions rather than comprehensive estimates of treatment-related risk.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Doxorubicin and Cyclophosphamide Followed by Paclitaxel, Trastuzumab, and Lapatinib in Treating Patients With HER2/Neu-Overexpressed Breast Cancer — NCT00482391.
• Registry record last updated 2017-05-12; status last verified 2017-04.
• Results first posted 2017-03-13.
• 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 II, single-group study of dose-dense doxorubicin and cyclophosphamide followed by weekly paclitaxel with trastuzumab and lapatinib in HER2/neu-overexpressed or amplified breast cancer. Enrollment is listed as 95; the study start is 2007-03 and primary completion is 2011-07. The primary endpoint is the number of patients who completed all planned therapy within 2 years. The endpoint result and its analysis denominator are not reported in the registry record.

The record lists evaluation for toxicity as a secondary outcome and reports selected adverse-event counts and terms. It lists 2 outcome measures and 0 analyses, but no statistical analysis plan or primary outcome estimate. The single-group design does not provide a described control comparison. The available information supports a description of the study question, regimen, design, and reported safety entries, but not a quantitative conclusion about primary endpoint completion or a comparative treatment effect.