Trastuzumab and Ixabepilone in Treating Women With HER2-Positive Metastatic Breast Cancer: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Trastuzumab and Ixabepilone in Treating Women With HER2-Positive Metastatic Breast Cancer (NCT00079326), a na phase 2 study. The primary outcome is Overall Response Rate.

2. Clinical Question

The clinical question is whether responses were observed among participants treated with this combination in this phase 2 study, and how precisely the response rate was estimated. Because there is no concurrent comparator, the study cannot directly estimate how the combination compares with another regimen or with no treatment. The registry’s description of the rationale for combining an antibody and a chemotherapy drug is not evidence of the size or certainty of a treatment effect. The posted record identifies the endpoint and its assessment criteria, but does not give the primary response result.

3. Trial Design

This was a phase 2 study sponsored by the National Cancer Institute (NCI). It is registered as a single-group trial, with allocation recorded as not applicable and masking listed as none. The registry reports enrollment of 39 participants. The study status is terminated; the reason for termination is not reported in the registry record.

The intervention group received trastuzumab and ixabepilone. The regimen description specifies trastuzumab by intravenous infusion over 30-90 minutes and ixabepilone by intravenous infusion over 3 hours on day 1. Courses were scheduled to repeat every 21 days while disease had not progressed and toxicity remained acceptable. Laboratory biomarker analysis is also listed as an intervention, but its role and results are not reported in the registry record.

The registry lists a start date of 2004-01 and a primary completion date of 2008-07. It identifies overall response rate as the primary outcome, with assessment up to 6 years, and time to treatment failure as a secondary outcome. The response definition uses RECIST v1.0 criteria and imaging by computed tomography or magnetic resonance imaging.

A single-group design can describe outcomes among participants who received the regimen, but it does not create a randomized control group. Differences from outcomes in other studies could reflect differences in participants, care, measurement, or follow-up, as well as treatment. The registry record does not report a protocol-level sample-size justification, the reason the study was terminated, or a detailed statistical analysis plan. The planning illustration associated with sample-size calculations is not the study’s design justification and does not constitute observed evidence of power.

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

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 Overall Response Rate, measured over Up to 6 years.

Overall response rate (ORR) is the percentage of participants classified as having either a complete response or a partial response. Under the registry’s RECIST v1.0 description, a complete response means disappearance of all target lesions. A partial response requires at least a 30% decrease in the sum of the longest diameter of target lesions. The registry specifies assessment using computed tomography or magnetic resonance imaging scans and gives a timeframe of up to 6 years.

Response rate is a binary-type endpoint at the participant level: each participant is classified according to whether the specified response criteria are met, and the group result is expressed as a percentage. In general, an endpoint definition matters because it determines what counts as an event and helps readers understand which clinical changes contribute to the result. A common response framework can make the endpoint more interpretable, although its practical application still depends on how assessments were scheduled, reviewed, and handled when information was unavailable.

The registry identifies the endpoint and its definition but does not report the number or percentage of participants with a response, the confidence interval, or details about the analysis population. The observed ORR and its precision are therefore not reported in the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

What does a single-group design estimate?

A single-group study follows participants who receive the study regimen and describes outcomes within that group. For a binary endpoint such as overall response, the basic quantity is the fraction of analyzed participants meeting the response definition, expressed as a percentage. In general, the estimate is informative about the observed group under the study’s eligibility, care, and assessment procedures. It does not by itself measure a causal difference between the regimen and an alternative.

Here, the registry classifies the model as single-group and reports no masking. Allocation is listed as not applicable. There is therefore no randomized control arm in the registry record. A comparison with results from a different trial would not be a like-for-like randomized comparison: participant characteristics, assessment schedules, and other study conditions may differ. The registry does not report a statistical adjustment intended to address such differences.

How should a response percentage be understood?

The primary endpoint classifies response using RECIST v1.0. Complete response requires disappearance of all target lesions; partial response requires at least a 30% decrease in the sum of the longest diameter of target lesions. ORR combines these response categories and is defined as a percentage of participants. In general, a percentage describes how common the specified outcome was in the analyzed group; its meaning depends on the denominator and on how participants without assessable measurements were handled.

The registry lists the endpoint and its timeframe as up to 6 years, but it does not report the observed response percentage, the confidence interval, the analysis denominator, or the handling of missing assessments. These omissions limit interpretation of both the estimate and the precision that would accompany it.

What does a confidence interval add?

In general, a confidence interval represents statistical uncertainty around an estimate, conditional on the method and assumptions used. It is not a guarantee that the true value lies within the interval, and it does not address every source of uncertainty. For example, it cannot correct a nonrepresentative study population or turn a single-group result into a randomized comparison. The primary endpoint is described as using a 95% confidence interval, but the estimate and interval are not reported in the registry record.

Why can event counts and analysis details matter?

For a percentage endpoint, readers need to know both how many participants met the endpoint and how many were included in its denominator. They also need to know how missing or unevaluable assessments were handled. In general, excluding participants without an assessment can yield a different result from treating them as not having a response. The registry record does not state which approach was used.

Time to treatment failure is listed as a secondary outcome. In general, time-to-event outcomes require information about event definitions, follow-up, and how participants without an observed event are handled. The registry does not report these details or a result for this outcome. The record lists zero analyses, so no outcome analysis results are posted there.

What is the role of planning calculations?

The registry-associated sample-size illustration is described as a planning exercise based on the observed effect, using a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. It considers an effect defined as a stated fraction of the observed effect. These assumptions describe a hypothetical planning calculation, not the single-group study’s observed design. The record does not report a protocol sample-size justification, and planning calculations are not observed power. No sample-size values from such calculations are needed to interpret the fact that the trial itself enrolled 39 participants in a single group.

In general, over-dispersion arises when variability is greater than a statistical model assumes. It can make standard errors and confidence intervals too small if ignored. That concept is relevant only when the endpoint and analysis model call for it; the registry does not report a model or an over-dispersion assessment for this study. It would not be appropriate to infer one from the endpoint description alone.

What can be concluded from the posted analysis record?

The endpoint definition gives a clear description of the intended response measure, but an endpoint definition is not an outcome result. The absence of reported results prevents assessment of the response estimate, its precision, and any statistical evidence associated with it. The registry also does not report multiplicity procedures, interim analyses, or a detailed statistical plan. Those elements should be treated as not reported in the registry record, rather than assumed to have been absent from the study itself.

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("Cohort 1: No Prior Chemo or Trastuzumab Treatment", "Cohort 2: 1-2 Prior Trastuzumab Treatment Regimens")
n      <- c(15, 24)
events <- c(11, 6)
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  Cohort 1: No Prior Chemo or Trastuzumab Treatment  15  11  73.3  44.9  92.2  48.0  89.1  47.6  89.0
ARM  Cohort 2: 1-2 Prior Trastuzumab Treatment Regimens  24  6  25.0  9.8  46.7  12.0  44.9  12.1  45.1

11. Multiplicity, Missing Data and Analysis Populations

The registry identifies overall response rate as the primary outcome and time to treatment failure as a secondary outcome. It also reports two outcome measures and zero analyses. No outcome analysis results are listed in the registry record, including a primary response estimate or a result for time to treatment failure.

Multiplicity refers, in general, to the increased chance of a false-positive finding when several hypotheses or outcomes are tested. Statistical plans may specify a primary outcome, testing sequence, or adjustment to address multiple comparisons. The registry record does not report a multiplicity procedure, a hierarchy of tests, or whether any interim analyses were planned or conducted. These details are not reported in the registry record; their absence from the listing should not be taken as proof of what was or was not done outside it.

The record does not describe the analysis population for ORR or how missing, unevaluable, or incomplete imaging assessments were handled. For a response percentage, the denominator and missing-data approach matter because participants without an assessable response may be treated differently across analysis strategies. Without those details, readers cannot determine which participants contributed to any intended estimate.

Time to treatment failure is a time-to-event outcome, but the registry does not give its event definition, censoring rules, analysis population, or result. These details are important in general because the meaning of a time-to-event estimate depends on what counts as an event and how follow-up ending before an event is represented.

The registry record does not report a detailed statistical analysis plan, sample-size justification, interim-analysis information, or missing-data methods. No conclusions about those choices should be inferred from the endpoint listing alone.

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: dysphagia (2.6%), leukocytes (2.6%), hypoxia (2.6%), febrile neutropenia (2.6%), alkaline phosphatase (2.6%).

For all study participants, the registry reports 39 at risk and 7 affected in its serious-adverse-event category. It separately reports 39 at risk and 39 affected for other adverse events. These are registry counts, and the categories should not be conflated: the entry for other adverse events is not the serious-adverse-event count.

The listed serious-event terms are dysphagia, leukocytes, hypoxia, febrile neutropenia, alkaline phosphatase, and vomiting. Each term is reported as 2.6%. The registry listing does not establish whether these terms represent unique participants, repeated episodes, or a specific severity grade beyond their placement in the serious-event listing. Event attribution to treatment is not reported in the registry record.

Counts alone do not describe when an event occurred, how long it lasted, whether it recurred, or what action followed. The record does not provide those details in the adverse-event summary. Deaths are not reported in the registry record. These figures therefore describe what is listed for safety reporting, not a complete characterization of individual risk or a comparison with another treatment group.

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

The study is a phase 2, single-group evaluation of trastuzumab with ixabepilone in women with HER2-positive metastatic breast cancer. Its stated primary endpoint is overall response rate, defined using RECIST v1.0. The registry reports enrollment of 39 and gives a regimen description and an assessment timeframe of up to 6 years.

The registry record does not report the observed ORR, the number of participants with complete or partial response, or the 95% confidence interval. As a result, the posted information does not establish the magnitude or precision of the response result. The record also does not report results for the secondary time-to-treatment-failure outcome.

Even if a response estimate were available, the single-group design would describe outcomes in the treated group rather than estimate a randomized difference against a control. It would not, on its own, establish what would have happened to the same participants under another treatment, or identify the separate contribution of trastuzumab and ixabepilone. The study’s background description of how the drugs may act is not a result of the clinical outcome analysis.

The safety listing records serious adverse-event counts and selected serious-event terms, but does not provide detail about timing, recurrence, attribution, or event management. The terminated status is recorded, while the reason for termination is not reported in the registry record.

In general, trial interpretation depends on the outcome estimate, its uncertainty, the analysis population, missing-data handling, and design. Several of these details are not reported in the registry record. The most defensible reading is therefore limited to the study’s design and stated measures, together with the posted adverse-event counts. It does not support a comparative treatment conclusion.

14. Why This Trial Matters Statistically

This trial illustrates why design and outcome reporting must be read together. A clearly defined response endpoint does not substitute for the response estimate itself. The registry specifies ORR, RECIST v1.0 criteria, imaging methods, and an assessment timeframe up to 6 years, yet does not report the primary result or its confidence interval. Without those values, neither the observed response frequency nor its statistical precision can be assessed.

The single-group design also sets a firm boundary on interpretation. It can describe outcomes among participants who received the combination, but it lacks a randomized comparator for estimating a treatment contrast. This distinction is central to biostatistical interpretation: an outcome observed after treatment is not, by itself, an estimate of what treatment changed relative to an alternative.

The record also highlights the importance of analysis transparency. The registry lists a secondary time-to-treatment-failure outcome but no analysis results. It does not report the analysis population, missing-data procedures, multiplicity approach, or interim-analysis details. These omissions make it difficult to evaluate how intended questions were translated into statistical analyses.

Finally, safety summaries need context. Counts and listed terms communicate which events were recorded, but they do not replace information on event timing, recurrence, attribution, and follow-up. The study’s terminated status is also relevant context, although the reason is not reported in the registry record. Together, these features show why registry design details, endpoint definitions, results, and analysis methods each play distinct roles in interpreting clinical evidence.

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 most direct limitation of the registry entry is that it does not report the primary overall response result or its confidence interval. The record therefore does not allow readers to assess the observed response percentage or its precision. It also does not report separate counts for complete and partial responses.

The study is single-group, with no randomized control arm. This limits interpretation to outcomes among participants receiving trastuzumab and ixabepilone and prevents a direct randomized comparison with another treatment. The registry lists enrollment of 39, but does not report the number included in the primary endpoint analysis or the analysis population definition.

Although the response criteria and imaging methods are described, the record does not report assessment schedules, independent review procedures, or how missing and unevaluable scans were handled. The endpoint timeframe is up to 6 years, but the registry does not provide follow-up completeness or the timing of response assessments.

The record lists time to treatment failure as a secondary outcome but does not report its definition, analysis, or result. It also does not report the statistical analysis plan, a sample-size justification, multiplicity procedures, or interim-analysis details. These items are not reported in the registry record and should not be inferred.

Safety information is limited to the listed counts and serious-event terms. The registry does not report event timing, recurrence, attribution, or management details in this summary. It records the study as terminated without reporting the reason for termination. These limitations constrain conclusions about both efficacy and safety from the registry entry.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Trastuzumab and Ixabepilone in Treating Women With HER2-Positive Metastatic Breast Cancer — NCT00079326.
• Registry record last updated 2014-06-02; status last verified 2013-01.
• Results first posted 2014-02-06.
• 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 describes a phase 2, single-group study sponsored by the National Cancer Institute (NCI), with enrollment of 39 and status listed as terminated. The study examined trastuzumab with ixabepilone in women with HER2-positive metastatic breast cancer. The regimen description specifies intravenous administration on day 1, with courses repeating every 21 days subject to disease progression or unacceptable toxicity.

The primary endpoint was overall response rate under RECIST v1.0, assessed by computed tomography or magnetic resonance imaging for up to 6 years. Time to treatment failure was listed as a secondary outcome. The ORR estimate, its confidence interval, and the secondary-outcome result are not reported in the registry record. The record lists serious adverse events among 7 of 39 at risk and other adverse events among 39 of 39 at risk; deaths are not reported in the registry record.

The registry does not report the reason for termination, analysis populations, missing-data methods, or a detailed statistical plan. The single-group design does not provide a randomized comparator.