Study of Combined Fulvestrant and Everolimus in Advanced/Metastatic Breast Cancer After Aromatase Inhibitor Failure: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Study of Combined Fulvestrant and Everolimus in Advanced/Metastatic Breast Cancer After Aromatase Inhibitor Failure (NCT00570921), a na phase 2 study. The primary outcome is Time to Progression.

2. Clinical Question

The clinical question is therefore about outcomes observed during treatment with the combination in a selected population, rather than about a randomized comparison between treatments. The registry lists objective response rate and clinical benefit rate as secondary outcomes, but their results are not reported in the registry record. The stated objective includes safety as well as efficacy; the adverse-event information recorded for the study is described separately.

Because there is no recorded comparator, the design cannot by itself distinguish outcomes associated with the treatment from outcomes that might have occurred under another treatment or without the study treatment. Its results, where reported, would describe the experience of participants in this study, with interpretation shaped by the endpoint definitions and the completeness of follow-up. The registry does not report enough information to assess comparative benefit or comparative safety.

3. Trial Design

This was a phase II study with a single-group model. The registry records enrollment of 33 and lists fulvestrant plus everolimus as the treatment group. Allocation is marked not applicable, and masking is listed as none. These design features mean that the registry does not describe random assignment or blinding, and it records no separate control group.

The study title and brief description place the treatment in advanced or metastatic breast cancer after aromatase inhibitor failure. The brief description specifies women with hormone receptor positive metastatic breast cancer. The primary objective was to assess whether fulvestrant combined with everolimus was effective and safe in that setting. The study status is completed. The recorded start is 2008-04, and the primary completion is 2013-02.

Enrollment describes the number recorded for the study, not necessarily the number included in every endpoint analysis. The registry record does not report endpoint-specific analysis populations, the number followed for the primary endpoint, or the number with evaluable response assessments. It also does not report the reasons participants may have been excluded from any analysis.

A single-group study can describe outcomes among participants receiving the treatment, but it does not estimate a treatment contrast against a concurrent control. Without randomization and a comparison group, differences between the observed outcomes and outcomes under another care strategy cannot be isolated. The absence of masking may also matter for outcomes involving investigator assessment or participant reporting, although the registry record does not describe assessment procedures.

The arm description includes a fulvestrant dosing schedule, but the recorded description of everolimus is incomplete. The registry record does not report enough information to reconstruct the full treatment regimen or determine how treatment exposure was handled in the analyses. It also does not report a statistical analysis plan, sample-size justification, or details of any interim analyses.

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: 2 were not evaluable as described in participant flow and not included in demographic table.

6. Primary Endpoint

The registry lists the primary outcome as Time to Progression, measured over Duration of time start of treatment to time of documented progression or death.

The primary endpoint is time to progression, measured in months. The registry defines its timeframe as the duration from treatment start to documented progression or death. This is a time-to-event endpoint: it represents the time until an event meeting that definition, rather than a single status assessment at a fixed visit.

Time-to-event endpoints are useful in clinical research when both whether an event occurs and when it occurs are relevant. They can account for participants whose event has not been observed by the end of available follow-up, provided the analysis handles such follow-up appropriately. In general, those participants contribute information up to the time their event status is no longer observed; this is commonly described as censoring. The registry record does not report the censoring rules or the analysis method used for this endpoint.

The median is the registered summary measure, and the planned dispersion measure is a 95% confidence interval. In general, the median time-to-event is the time by which half of the relevant event-time distribution has experienced the event, subject to the estimator and data handling used. A confidence interval communicates uncertainty around the estimate; it is not a range guaranteed to contain the underlying value. Neither the median estimate nor its 95% confidence interval is reported in the registry record, so the endpoint magnitude and its precision cannot be assessed from the recorded information.

The definition includes death as an event as well as documented progression. That combined definition is important when interpreting the endpoint: it is not a measure of progression alone. The registry does not report separate results for progression and death.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

What does a median time-to-event estimate describe?

Time-to-event methods describe the timing of a defined event while allowing follow-up times to differ between participants. For this study, the event definition combines documented progression or death, and the time origin is treatment start. The registered summary is the median time-to-event in months. In general, the median is a distributional summary: it identifies the time by which half of the event-time distribution has reached the event, according to the estimator used. It is not the average follow-up time, and it does not show the full pattern of event timing.

Time-to-event data often include incomplete observation. A participant may leave follow-up or reach the end of observation without a recorded event. Such records are commonly handled as censored observations, which contribute information while the participant's event status is known. The validity of the resulting estimate depends on how censoring is defined and on assumptions about the relationship between censoring and event risk. The registry record does not report the censoring rules, follow-up distribution, or estimator used, so those aspects cannot be evaluated.

What does a 95% confidence interval communicate?

The registry identifies a 95% confidence interval as the dispersion measure for the primary endpoint. In general, a confidence interval expresses the statistical uncertainty associated with an estimate under the method's assumptions. A narrower interval indicates greater precision than a wider interval, but does not establish that the estimate is unbiased or clinically important. The interval is not a guarantee that the true value lies within its endpoints. Because neither the interval nor the median is reported in the registry record, the precision of this endpoint estimate cannot be judged.

How should a hazard ratio be read?

In general, a hazard ratio compares event rates over time between groups, under the assumptions of the model used. It is a relative measure, not a direct estimate of how many months separate the groups, and its interpretation depends on the comparison and the time-to-event model. The study is recorded as single-group and no sponsor-reported hazard ratio is included in the registry information. A comparative hazard ratio would require an identifiable comparison; it should not be inferred from the single-group design or from the endpoint title. The registry record does not report a hazard-ratio estimate or its confidence interval.

Why does a single-group design limit causal interpretation?

General statistical principle: a concurrent control group helps distinguish outcomes under an intervention from outcomes that could arise under another treatment or care strategy. Random allocation is used to reduce systematic differences between groups, while masking can limit some forms of assessment bias. This study is listed as single-group, with allocation not applicable and masking none. There is therefore no randomized contrast in the registry record. Observed outcomes can be described for participants in the study, but the design cannot establish what their outcomes would have been under an alternative treatment.

The lack of masking is relevant in general when outcomes involve judgments or reports that might be influenced by knowledge of treatment. The registry record does not report the procedures for progression assessment, the use of independent review, or how assessments were standardized. It is therefore not possible to determine how assessment decisions were protected against expectation or measurement effects.

What does over-dispersion mean in general?

Over-dispersion occurs when observed variability is greater than a statistical model expects. In count outcomes, a simple model may assume that the mean and variance are linked in a particular way; if the data vary more than that assumption allows, standard errors can be too small and confidence intervals too narrow. Models that account for extra variability may be appropriate when their assumptions fit the data. This is a general concept and does not establish that over-dispersion occurred in this study. The registry record does not describe a count model or report a diagnostic assessment of over-dispersion.

How should planning calculations be distinguished from results?

Sample-size planning asks how much information a future study might need under specified assumptions. A planning illustration based on an observed effect is not a measure of power achieved by the completed study. It also does not show that the original trial was designed with those assumptions. The registry record does not report the study's own sample-size justification. The assumptions recorded for planning illustrations describe a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation, with the effect expressed as a stated fraction of the observed effect. Those assumptions are not the design of this single-group trial and should not be read as evidence that the study had a randomized two-arm analysis.

The recorded guidance distinguishes time-to-event planning outputs, which use a total event count, from other planning outputs, which use participants per arm. These are planning conventions, not observed study results. No specific planning output is included in the registry information. The enrollment of 33 is the registry's enrollment figure; it does not, on its own, establish how many participants had complete endpoint follow-up or were included in each analysis.

What can be learned from the registered outcomes?

The outcome list identifies time to progression as primary and objective response rate and clinical benefit rate as secondary. These names indicate the broad outcomes of interest, but they do not give the operational definitions, assessment schedules, handling of unevaluable participants, or analysis populations. The registry record does not report those details. Nor does it report the primary estimate, interval, or secondary outcome results in the information. Statistical methods can clarify how such results should be interpreted, but they cannot substitute for the missing estimates and analysis details.

10. Multiplicity, Missing Data and Analysis Populations

The registry lists time to progression as the primary outcome and objective response rate and clinical benefit rate as secondary outcomes. Considering multiple outcomes can raise a multiplicity issue: when many statistical hypotheses are tested, the chance of at least one apparently notable result can increase. In general, a prespecified hierarchy, adjustment, or clearly exploratory interpretation can help readers understand how multiple outcomes are handled. The registry record does not report a multiplicity strategy, a testing hierarchy, or whether secondary outcomes were intended as confirmatory or exploratory.

The record states that there are three outcome measures and three analyses, but does not describe all of those measures or analyses in the information. It does not report which populations were used, whether analyses were prespecified, or how the analysis of each outcome was conducted. The statistical analysis plan is not reported in the registry record, so the relationship between the registered outcomes and the analyses cannot be assessed.

Missing-data handling is also not reported. For time-to-event analysis, the treatment of incomplete follow-up and censoring affects how estimates are formed. For response outcomes, missing or unevaluable assessments can affect the denominator and the interpretation of the reported rate. These are general considerations, not claims about what happened in this trial. The registry record does not report the extent of missing outcome data, reasons for missingness, imputation procedures, or sensitivity analyses.

Analysis populations are not identified. Enrollment of 33 does not establish that all enrolled participants contributed to every endpoint analysis. The registry record does not say whether the primary analysis included all enrolled participants, only those who began treatment, or another defined population. It also does not report endpoint-specific denominators. These omissions limit assessment of representativeness, attrition, and robustness.

Without outcome estimates, analysis populations, and missing-data methods, readers cannot judge how the primary and secondary results were calculated or how sensitive they might be to analytic choices. These elements are not reported in the registry record.

11. 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: left ventricular thrombus (3.0%), acute cholecystitis (3.0%), pneumonia (3.0%), nausea (3.0%), renal failure (3.0%).

The registry records 33 participants at risk for serious adverse events, with 5 affected, and 33 at risk for other adverse events, with 31 affected. These are separate registry categories and should not be combined. The record lists left ventricular thrombus, acute cholecystitis, pneumonia, nausea, and renal failure among the serious-event terms, each at 3.0%.

These figures describe safety reporting for the treatment group, not a comparison with an untreated or alternative-treatment group. The percentages should be quoted as recorded rather than recalculated from the counts. The listed terms do not establish that each event was caused by treatment, and the record does not report attribution, timing, duration, severity grades, or management details for each term. It also does not clarify whether one participant could contribute more than one event term or whether event categories overlap.

The registry lists deaths as null, which means death information is not reported in the registry record. It should not be interpreted as a recorded count of zero. Likewise, the absence of an event term from the short list of serious terms should not be taken to mean that the event did not occur. Safety interpretation is limited by the single-group design, the lack of comparative data, and the event details not reported in the registry record.

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

The registry record establishes that a phase II, single-group study evaluated fulvestrant plus everolimus in advanced or metastatic breast cancer after aromatase inhibitor failure. It identifies time to progression, defined from treatment start to documented progression or death, as the primary endpoint. It also records objective response rate and clinical benefit rate as secondary outcomes. These registry entries describe the research question, not the size or direction of an observed treatment effect.

The primary endpoint's median and 95% confidence interval are not reported in the registry record. The secondary outcome results are also not reported. Consequently, the posted information does not establish how long participants remained free of the defined event, how uncertain any estimate was, or what response and clinical benefit rates were observed. A missing registry result is not evidence that the endpoint had no events or that the treatment had no effect.

The design does not support a direct treatment comparison because it has no concurrent comparator and is not randomized. Any outcomes reported for the group would describe participants enrolled in this study. They would not, by themselves, show what would have happened to those participants under another treatment. The lack of masking may also matter for outcomes involving assessment, but the procedures needed to evaluate that concern are not reported in the registry record.

The safety entries document adverse events as recorded, including serious adverse events affecting 5 participants and other adverse events affecting 31 participants. They do not establish comparative safety or causation. The event details and deaths information are incomplete in the registry record.

Overall, the available record identifies a clinically focused study question and records enrollment and safety information, but does not contain the primary or secondary outcome estimates needed to judge observed efficacy or precision. It cannot support a conclusion about whether the treatment works or does not work. More complete outcome and analysis reporting would be needed to evaluate the endpoint results, their uncertainty, and the limitations of the study design.

13. Why This Trial Matters Statistically

This trial matters statistically because its design and endpoint illustrate the distinction between describing outcomes and estimating a treatment effect. The registry records a single-group study of fulvestrant plus everolimus. Such a design can document what happened among participants receiving the combination, but it has no concurrent comparison group from which to estimate a randomized contrast. That distinction is central when interpreting any outcome reported for the study.

The primary endpoint is time to progression, with death included in the event definition. This is a time-to-event outcome, so both timing and incomplete follow-up can affect its analysis. A median and confidence interval would help communicate the observed event-time distribution and the precision of the estimate. The registry identifies those summaries but does not report their values. The endpoint definition alone cannot show the outcome's magnitude.

The record also illustrates why registration details and outcome reporting serve different roles. The study question, treatment group, and endpoints are identifiable, but secondary outcome estimates, analysis populations, missing-data procedures, and the statistical analysis plan are not reported in the registry record. Without these details, readers cannot fully assess how the results were derived, even if estimates are available from another source.

Safety figures require similar care. Counts and percentages in a single treatment group describe recorded events, but they do not establish that treatment caused an event or that its risk differs from another care strategy. A comparator and clear event definitions are important for comparative safety interpretation.

Finally, planning illustrations should not be confused with observed power or with the original study rationale. They are conditional calculations based on assumptions, whereas the registry's enrollment is a recorded study characteristic. Keeping these concepts separate supports a more precise reading of both trial design and statistical evidence.

14. 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 limitation in interpreting this trial from the registry record is that the primary endpoint estimate and its confidence interval are not reported. The record names the endpoint and its intended summary, but does not provide the values needed to assess the observed time to progression or its precision. Secondary outcome results are also not reported in the registry record.

The single-group design has no concurrent control and no recorded random allocation. It therefore cannot provide a randomized comparison or isolate treatment effects from other influences on outcomes. Masking is recorded as none. The registry record does not describe progression assessment procedures, independent review, or safeguards against assessment bias, so the effect of unmasked assessment cannot be evaluated.

Important analysis details are not reported, including the statistical analysis plan, the analysis population for each endpoint, endpoint-specific denominators, censoring rules, and missing-data methods. The registry does not report the sample-size justification or any interim-analysis plan. These absences limit assessment of prespecification, completeness of follow-up, and the robustness of estimates.

The available safety information is also limited. Although serious and other adverse-event counts are recorded, event attribution and detailed event-level context are not reported. Deaths are listed as null, so death information is not reported in the registry record. A null entry should not be interpreted as a zero count.

The arm description gives some fulvestrant administration details but truncates the everolimus description. The full treatment regimen therefore cannot be reconstructed from the registry record. The record also does not report enough information to establish whether enrollment corresponds to the population analyzed for each outcome. These limitations constrain interpretation of both efficacy and safety findings.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Study of Combined Fulvestrant and Everolimus in Advanced/Metastatic Breast Cancer After Aromatase Inhibitor Failure — NCT00570921.
• Registry record last updated 2017-02-23; status last verified 2017-01.
• Results first posted 2014-12-31.
• 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.

18. Record Summary

The registry identifies NCT00570921 as a completed phase II study of combined fulvestrant and everolimus in advanced or metastatic breast cancer after aromatase inhibitor failure. The recorded study model is single-group, allocation is not applicable, and masking is none. Enrollment is 33. The recorded start is 2008-04, and primary completion is 2013-02.

The primary endpoint is median time to progression in months, with a 95% confidence interval. Its timeframe runs from treatment start to documented progression or death. Objective response rate and clinical benefit rate are listed as secondary outcomes. Their results, and the primary endpoint estimate and interval, are not reported in the registry record.

The safety record lists 5 participants affected by serious adverse events and 31 affected by other adverse events, each with 33 at risk. Several serious-event terms are recorded at 3.0%. The record does not provide a comparator or the details needed for causal safety interpretation. The statistical analysis plan, missing-data procedures, and analysis populations are not reported in the registry record.