Temsirolimus in Treating Patients With Locally Advanced or Metastatic Breast Cancer: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Temsirolimus in Treating Patients With Locally Advanced or Metastatic Breast Cancer (NCT00376688), a na phase 2 study. The primary outcome is Clinical Benefit Rate (Complete Response, Partial Response, or Stable Disease).

2. Clinical Question

3. Trial Design

This was a phase II, single-group study of temsirolimus in patients with locally advanced or metastatic breast cancer. The registry records enrollment of 31, identifies the study as completed, and lists the National Cancer Institute as sponsor. The recorded start date is 2006-07-11, and primary completion is recorded as 2008-06-12.

Participants in the treatment group received temsirolimus intravenously over 30 minutes weekly. Treatment courses repeated every 28 days in the absence of disease progression or unacceptable toxicity. The registry also lists laboratory biomarker analysis, without further description of its procedures or how its findings were to be used.

The design has no randomized allocation or masking: allocation is listed as NA, masking as none, and the model as single group. Thus, there is no control arm for estimating how outcomes might have differed without temsirolimus or under another treatment. Any observed response proportion would describe the participants treated in this study; by itself, it would not separate treatment effects from other influences on outcome.

The primary outcome is clinical benefit rate, defined as the proportion with complete response, partial response, or stable disease for at least 24 weeks. Response was evaluated using RECIST version 1.0. The endpoint timeframe is listed as up to 24 months. Although one outcome measure is listed, the registry record does not report the endpoint result or any analysis output. Further information about eligibility criteria, recruitment, analysis populations, follow-up completeness, and the protocol’s statistical plan is not reported in the registry record.

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.

Population: Entire study population

6. Primary Endpoint

The registry lists the primary outcome as Clinical Benefit Rate (Complete Response, Partial Response, or Stable Disease), measured over Up to 24 months.

The primary endpoint is clinical benefit rate, expressed as the percentage of participants with a complete response, partial response, or stable disease maintained for at least 24 weeks. The registry says response was assessed using RECIST version 1.0. For target lesions, complete response means disappearance of all target lesions; partial response requires at least a 30% decrease in the sum of the longest diameters relative to baseline; stable disease means neither enough shrinkage for partial response nor enough increase for progressive disease, using the smallest sum since treatment began as reference. The description also gives criteria for non-target lesions, including disappearance of all non-target lesions and normalization of tumor marker level for complete response.

A combined endpoint can capture more than tumor shrinkage alone: it includes participants whose disease meets the study’s stable-disease definition for the required duration. That can be useful in a phase II setting when the question is whether a treatment is associated with a defined degree of disease control. This is a general explanation of the endpoint concept, not a result for this study.

The registry lists the endpoint timeframe as up to 24 months, while the clinical-benefit definition requires stable disease to persist for at least 24 weeks. These describe different aspects of the endpoint: the timeframe indicates the stated observation window, and the duration criterion is part of the outcome definition. The registry record does not report how many participants met the definition or the resulting percentage.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The available information identifies the trial as a phase II, single-group study with a percentage-based primary endpoint. It does not describe the protocol’s statistical analysis plan. Statistical concepts below are general explanations of how such outcomes and designs are commonly interpreted; they are not claims about methods used in this trial unless explicitly stated in the registry record.

What does a percentage endpoint represent?

Clinical benefit rate is a proportion: the numerator is the number of participants meeting the endpoint definition, and the denominator is the relevant analysis population. Here, the endpoint definition includes complete response, partial response, or stable disease for at least 24 weeks. The registry record does not report the numerator, the analyzed denominator, or the resulting percentage. The recorded enrollment of 31 should not be assumed to be the denominator used in an analysis, because the analysis population and handling of participants without evaluable outcomes are not reported in the registry record.

A percentage alone is a point estimate. It describes the observed fraction in the group analyzed, but does not convey all the uncertainty that arises from studying a limited number of participants. A confidence interval expresses a range of values compatible with the data under the method’s assumptions. A narrow interval indicates greater precision than a wide interval. No confidence interval is reported for this endpoint, so the precision cannot be assessed from the registry record.

Why does the single-group design matter?

A single-group study observes outcomes under one treatment condition. It can describe the outcomes recorded among participants in that group, but it cannot directly estimate a between-group contrast. In a randomized comparison, random allocation is intended to make the groups comparable on average, allowing the treatment contrast to be interpreted with fewer concerns about systematic group differences. This study has no randomized comparator: allocation is NA and the model is single group. Any comparison with outcomes from another population or study would require assumptions about comparability that are not established by this record.

The masking field is listed as none. In general, lack of masking can influence outcome assessment when judgments are involved, although the endpoint uses stated response criteria. The record does not report whether independent review was used, how assessments were conducted, or whether the assessment process included safeguards against bias. No specific assessment procedure beyond RECIST version 1.0 is described.

How should response criteria be understood?

RECIST version 1.0 provides the stated framework for classifying response. The registry defines complete response, partial response, and stable disease for target lesions, and supplies criteria for non-target lesions. The combined clinical-benefit endpoint additionally requires stable disease to last at least 24 weeks. Requiring duration can distinguish sustained stable disease from a classification observed at a single assessment. The record does not explain the assessment schedule, how borderline or unevaluable assessments were resolved, or how participants who stopped treatment before the required duration were classified.

What do the planning assumptions mean?

The registry’s planning illustration is described as based on the 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 expressed as a stated fraction of the observed effect. These are assumptions for a hypothetical planning exercise, not a description of the actual single-group study design. They do not establish that this trial randomized participants or used those assumptions for its own sample-size planning.

Planning sample sizes are illustrations of how much information a future comparison might require under stated assumptions. They are not observed power, and they do not reveal the probability that the completed study demonstrated a treatment effect. The registry record does not report the original sample-size justification or its own planned statistical analysis. The numbers of participants per arm in any planning illustration are not stated in the record available for this analysis.

Why can over-dispersion matter?

General: statistical models often make assumptions about how variable outcomes are around their expected values. Over-dispersion means the observed variation is greater than a model assumes. If ignored, standard errors may be too small and confidence intervals too narrow, making results appear more precise than warranted. This concept is most directly relevant when the chosen model has a variance assumption that can be violated. The registry record does not identify a model for the clinical benefit endpoint, report a dispersion estimate, or state that over-dispersion was assessed. It would therefore be inappropriate to claim that it occurred or that a particular correction was applied in this study.

Overall, the record establishes the outcome definition and basic design but does not provide the result or sufficient analysis details to reproduce its statistical interpretation. Methods such as confidence intervals, regression adjustment, or sensitivity analyses should not be attributed to the trial because they are not reported in the registry record.

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("Treatment (Temsirolimus)")
n      <- c(31)
events <- c(3)
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  Treatment (Temsirolimus)  31  3  9.7  2.0  25.8  3.3  24.9  3.5  25.0

11. Multiplicity, Missing Data and Analysis Populations

Multiplicity arises when a study examines multiple outcomes, time points, subgroups, or statistical tests. If many hypotheses are tested, the chance of at least one apparently notable result can increase unless the analysis plan accounts for the number and structure of tests. The registry lists one outcome measure and does not list analyses. That does not establish that only one outcome was collected or that no additional analyses were performed; the full statistical plan and analysis history are not reported in the registry record.

The registry record does not describe an adjustment for multiple comparisons, a hierarchy among outcomes, planned subgroup analyses, or interim analyses. Those procedures should not be assumed. The primary endpoint is clearly named, but the record does not give a statistical testing procedure, a confidence interval method, or a rule for interpreting a result.

Missing-data handling is also not reported in the registry record. There is no description of how participants with missing response assessments, early discontinuation, or insufficient follow-up were handled in the clinical benefit rate. Since the endpoint requires stable disease to persist for at least 24 weeks, outcome ascertainment depends on information over time. Without the assessment and missingness rules, readers cannot determine the assumptions behind any endpoint calculation.

The analysis population is not reported in the registry record. The recorded enrollment is 31, but this does not establish how many participants were included in an endpoint analysis or whether all enrolled participants were evaluable. The record also does not report exclusions, withdrawals, protocol deviations, or reasons for missing outcomes. These gaps limit interpretation of both the denominator and the potential for bias related to incomplete outcome data.

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 (16.1%), death nos (9.7%), abdominal pain (6.5%), nausea (6.5%), platelet count decreased (6.5%).

The registry safety summary lists 31 participants at risk for serious adverse events, of whom 9 were affected. For other adverse events, it lists 31 at risk and 16 affected. These are participant counts in distinct registry categories; they do not state how many events each affected participant experienced. The registry does not provide event timing, duration, severity grading beyond the serious-event classification, or causal attribution to temsirolimus.

The listed serious adverse-event terms include Dyspnea at 16.1%, Death NOS at 9.7%, Abdominal pain at 6.5%, Nausea at 6.5%, Platelet count decreased at 6.5%, and Vomiting at 6.5%. These percentages are reported for the listed terms. They should not be read as comparative risks because there is no control group. The aggregate deaths field is not reported in the registry record, so Death NOS in the term list should not be substituted for a separate overall death count.

Safety counts describe events recorded in this study group, not the risk under an alternative treatment or no treatment. The record does not report definitions for all adverse-event categories, event-level detail, or the full method used to collect and classify these events. The listed counts and terms therefore support a limited descriptive reading rather than a causal or comparative conclusion.

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

The registry record documents a phase II, single-group study of temsirolimus in patients with locally advanced or metastatic breast cancer. It specifies the treatment schedule and defines the primary endpoint using RECIST version 1.0: clinical benefit is complete response, partial response, or stable disease maintained for at least 24 weeks. These details explain what the trial was designed to observe.

The record does not report the primary endpoint result. There is no stated clinical benefit percentage, response count, confidence interval, or p-value. As a result, the posted registry information does not establish the observed level of clinical benefit or how precisely it was estimated. A completed study status is not a substitute for those outcome data, and an unreported result should not be interpreted as either a positive or a negative finding.

The single-group design also sets a limit on what the study could establish. Outcomes in the treated group cannot be compared directly with outcomes under another treatment or a control condition. Without random allocation to a comparator, differences from external data could reflect differences in participants, care, assessment, or follow-up as well as treatment. No causal treatment contrast is reported.

The safety summary records affected participants and selected serious adverse-event terms, but it does not include a control group, event-level detail, or causal assessments. These data describe what the registry lists for the treatment group; they do not determine whether an event was caused by treatment or how its frequency compares with another condition.

In general, a well-defined endpoint makes a trial’s question more interpretable, but meaningful conclusions also depend on reported results, analysis populations, uncertainty, and the design’s ability to support comparisons. Several of these elements are not reported in the registry record. The appropriate reading is therefore limited to the study’s design, intended outcome definition, and listed safety summaries, without asserting an efficacy or safety conclusion.

14. Why This Trial Matters Statistically

This trial illustrates an important distinction in clinical-trial interpretation: an endpoint definition is not an endpoint result. The registry states what qualifies as clinical benefit, including the response categories and duration criterion, but does not report how many participants met that definition. Statistical readers must separate the clarity of a measurement rule from evidence about the observed outcome.

It also demonstrates why design determines the scope of inference. A single-group phase II study can describe outcomes among participants receiving the study treatment. It does not provide the randomized, like-for-like contrast that would directly estimate how outcomes differ between treatment strategies. This is a general design principle, and it is particularly relevant when interpreting a percentage outcome without a comparator.

The safety record further shows why counts, event terms, and causal conclusions are not interchangeable. The registry gives participant counts and selected serious-event percentages, but not a control-group comparison or detailed event histories. Descriptive safety reporting is useful, yet it cannot on its own establish comparative risk or causation.

Finally, this record underscores the role of transparent reporting. Interpretation of a binary endpoint depends on the denominator, handling of missing assessments, analysis population, and uncertainty estimate. These details are not reported in the registry record. Without them, readers cannot judge precision or determine how incomplete follow-up may affect an outcome estimate. The trial is statistically informative as an example of how design and reporting constrain conclusions, even though the primary outcome result itself is not reported.

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 principal trial-specific limitation is the absence of a reported primary endpoint result. The registry identifies clinical benefit rate as the outcome but does not give the number or percentage meeting the definition, nor an estimate of uncertainty. The record therefore cannot support a quantitative interpretation of the primary outcome.

The single-group design provides no internal control comparison. Allocation is listed as NA, masking as none, and the model as single group. This means that the record does not provide a direct estimate of the difference between temsirolimus and another treatment or control condition. The registry does not report a comparator, randomization procedure, or blinded outcome review.

The enrollment is recorded as 31, but the endpoint analysis population and denominator are not reported in the registry record. Nor are missing assessments, withdrawals, follow-up completeness, or the handling of participants who did not remain under observation long enough to satisfy the duration criterion. These details are especially relevant to an outcome that includes stable disease lasting at least 24 weeks.

Other important methodological details are also absent: the original sample-size justification, statistical analysis plan, multiplicity procedures, interim analyses, assessment schedule, and analysis methods. Their absence from the registry record should not be taken to mean that none existed; they are simply not reported in the available record. The listed safety summaries do not include a control group, event-level information, or an aggregate deaths value.

These limitations restrict interpretation to the documented design, endpoint definition, and safety entries. They prevent a quantitative conclusion about clinical benefit, precision, comparative effects, or causal attribution of adverse events.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Temsirolimus in Treating Patients With Locally Advanced or Metastatic Breast Cancer — NCT00376688.
• Registry record last updated 2020-02-24; status last verified 2020-01.
• Results first posted 2014-05-26.
• 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 sponsored by the National Cancer Institute. Enrollment is recorded as 31. Participants received weekly intravenous temsirolimus over 30 minutes, with courses repeating every 28 days in the absence of disease progression or unacceptable toxicity. The primary endpoint was clinical benefit rate, defined as complete response, partial response, or stable disease for at least 24 weeks using RECIST version 1.0.

No primary endpoint result, confidence interval, p-value, analysis population, or missing-data approach is reported in the registry record. The safety summary lists 9 of 31 participants affected by serious adverse events and 16 of 31 affected by other adverse events, alongside selected serious-event terms. With no comparator and no reported primary outcome estimate, the record supports description of the study design and endpoint definition, but not a quantitative efficacy conclusion or comparative safety assessment.