Multicenter Follow Up Study Of Subjects Who Participated In An Original Protocol Of Exemestane Vs. Megestrol Acetate In Postmenopausal Women With Metastatic Breast Cancer: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Multicenter Follow Up Study Of Subjects Who Participated In An Original Protocol Of Exemestane Vs. Megestrol Acetate In Postmenopausal Women With Metastatic Breast Cancer (NCT01237327), a registered phase 3 study. The primary outcome is Overall Survival.

2. Clinical Question

Statistically, the central question is whether the record provides an interpretable estimate of survival for each treatment group, and whether any contrast between those groups can be attributed to treatment. The outcome definition is clear, but the available information does not include the observed survival estimates or a reported comparative effect. In addition, the follow-up record does not state how participants were allocated to groups, and it warns against treating the arms as a direct controlled comparison. Those features limit the conclusions that can be drawn about differences between treatments.

The clinical context is a population with metastatic breast cancer after progression on anti-estrogens, sometimes following anti-estrogens plus chemotherapy. The record describes long-term follow-up of participants in an earlier study, rather than a separately described new comparison beginning at extension enrollment. That distinction matters: survival is anchored to the start of core-study treatment, while participation in the extension depended on consent. The registry record does not report whether those who entered the extension differed in relevant ways from those who did not.

Other listed outcomes are objective response rate, duration of response, time to tumor progression, and time to treatment failure. Their presence indicates additional clinical questions, but results for those outcomes are not reported in the registry record. The primary endpoint and the additional outcomes therefore cannot be used to quantify treatment benefit or harm.

3. Trial Design

The record describes a multicenter follow-up study of participants from an earlier exemestane-versus-megestrol acetate protocol. The original study is described in the official title as open-label, randomized, parallel-group, and phase III. The follow-up record itself is distinct: its stated purpose is long-term follow-up, and the registry caution says allocation in the follow-up is not stated and the arms are not a like-for-like control comparison. The original study’s design features should therefore not be assumed to establish the design or allocation process of the extension.

The recorded enrollment is 84. The primary outcome population is defined as participants randomized to study medication in the core study who consented to participate in the extension. That definition makes extension consent part of the analysis population. The record does not explain how many eligible core-study participants did not consent, or whether the extension participants differed from those who were not followed.

The interventions listed are exemestane and megestrol acetate. Arm descriptions are blank, so the registry does not give further detail about treatment exposure in the extension. In particular, it does not report whether participants continued treatment, switched treatment, stopped treatment, or were followed regardless of ongoing treatment. These details should not be inferred from the arm labels.

The recorded study status is completed. The registry lists a start in 2001-11 and primary completion in 2007-12. The primary outcome timeframe is every 12 weeks up to 6 years. The timing indicates the intended follow-up schedule, but the record does not provide visit-level completeness, follow-up duration for individual participants, or the number of deaths observed.

For a randomized treatment comparison, allocation can help make groups comparable at baseline. That principle applies to the core study as described, but the extension’s comparison cannot be treated as a continuation of randomized allocation without further information. Consent-based selection and any subsequent treatment decisions could affect group comparability. The registry record does not report the statistical adjustments, if any, used to address these issues. The sponsor is Pfizer.

4. Participant Flow and Accounting

The registry reports how participants moved through each stage of the study. All counts below are exactly as posted; missing counts are not inferred from other stages.

Before assignment: Follow-up study for participants in core study who completed 26 weeks of treatment, progressed while on therapy, or dropped out for any reason. Those who benefitted from core study treatment continued according to original randomization. Those who dropped out of core study received therapy appropriate for disease and were followed for survival.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: Intent-to-treat (ITT): participants randomized to study medication in core study who consented to participation in extension 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 Survival, measured over Every 12 weeks up to 6 years.

Overall survival is defined as the time in months from the date treatment began in the core study to the date of death from any cause. The registry lists assessment every 12 weeks up to 6 years. Because death from any cause is the endpoint, it does not depend on deciding whether a death was caused by breast cancer or by another event. The time origin is the beginning of core-study treatment, not the start of the extension follow-up.

Survival outcomes are commonly analyzed as time-to-event data because participants may be followed for different lengths of time, and some may still be alive when observation ends. A median survival summarizes the time by which half of the relevant population has experienced the event, when that median can be estimated. A confidence interval describes statistical uncertainty around an estimate; it does not guarantee that the true value lies within the reported interval.

The registry identifies the primary summary as a median with a 95% confidence interval. However, the median estimates and their confidence intervals are not reported in the registry record. Nor are the numbers of deaths, survival curves, or a comparative effect reported. The endpoint definition and assessment timeframe alone are not enough to determine the observed survival experience or the precision of a treatment-group contrast.

Overall survival is a clinically meaningful endpoint because it concerns time until death from any cause. In this follow-up, interpretation also depends on the population that consented to extension participation, how follow-up was maintained, and whether censoring or missing outcome information could have differed across groups. Those analysis details are not reported in the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

Statistical methods determine how observations become estimates and how much uncertainty accompanies those estimates. The registry identifies a median and 95% confidence interval for overall survival, a time-to-event endpoint. It does not report the survival estimates, the confidence intervals, or a detailed statistical analysis plan. The following concepts explain how such results are generally interpreted; they do not establish which procedures were used in this study.

What does a median survival describe?

For a time-to-event outcome, the median is the time at which the estimated survival experience reaches the point where half the population has experienced the event. Estimation can account for participants whose event has not been observed by the end of their follow-up. Such participants are typically censored at their last known time without the event. Censoring is informative only under assumptions about how the end of observation relates to the underlying event time. The registry record does not report the number censored, the censoring rules, or whether those assumptions were assessed.

A median is a summary of the survival distribution, not a description of every participant’s experience. Two groups can have similar medians while differing at other points in follow-up, or have different medians with substantial uncertainty. Survival curves and the amount of follow-up information help show the pattern over time, but those results are not reported in the registry record.

What does a confidence interval add?

A 95% confidence interval communicates uncertainty in an estimate using a procedure with a stated long-run coverage property under its assumptions. A narrow interval generally indicates greater precision than a wide interval. The interval is not a guarantee about the true value, and it does not by itself establish clinical importance. For a comparison, an interval for a treatment effect can show which effects are compatible with the data under the model. Here, the registry names a 95% confidence interval for the median but does not report its bounds, so neither its width nor the precision of the median can be judged.

Confidence intervals should be considered alongside the analysis population, event count, follow-up, and assumptions. The registry describes the primary population as core-study participants randomized to medication who consented to extension participation. It does not report the flow of eligible participants into the extension, the completeness of follow-up, or the amount of outcome information contributing to the estimate. Those omissions make it difficult to assess the stability and representativeness of an estimate even if one were available.

How are groups compared for time-to-event outcomes?

Common approaches include comparing survival curves or estimating a hazard ratio with a time-to-event model. A hazard ratio compares the rates of event occurrence at a given time among participants still at risk, subject to the model and its assumptions. It is not the same as a ratio of median survival times, and it does not directly give the absolute difference in survival probability. Some models assume that the relative hazard is reasonably constant over time; if that assumption does not hold, a single hazard ratio may conceal changes in the relative pattern. The record does not report a hazard ratio, survival curves, model specification, or checks of model assumptions.

Randomization in the core study can support a causal comparison when allocation is maintained and analysis follows the randomized groups. The extension record, however, states that allocation is not stated and warns that the arms are not a like-for-like control comparison. Therefore, a contrast between extension groups should not automatically be interpreted as the causal effect of treatment. Differences in extension participation, post-core treatment, or follow-up could contribute to any observed contrast. The record does not report adjustment methods that might address measured differences.

Why do follow-up and censoring matter?

Time-to-event analyses use both whether an event occurred and how long participants were observed. Participants who are alive at the end of their observed follow-up do not have a known death time within that period; their information contributes up to their censoring time. If loss to follow-up is related to prognosis, and that relationship is not adequately handled, estimated survival can be biased. The registry record does not describe loss to follow-up, censoring, missing-data procedures, or sensitivity analyses. It also does not provide the number of deaths, so the event information underlying the endpoint cannot be evaluated.

The scheduled outcome timeframe is every 12 weeks up to 6 years. That is a stated assessment schedule, not evidence that every participant completed every assessment or was followed for the full interval. The start and primary-completion dates describe the study record’s timing but do not reveal individual observation times or the completeness of outcome ascertainment.

What do planning illustrations mean?

Sample-size calculations are planning tools. They describe how much information a hypothetical study might require under assumptions about the effect to detect, significance level, allocation, and statistical model. They are not observed power and do not establish that a completed study had adequate power. In this record, any planning illustration is described as based on a fraction of the observed effect, with a two-sided significance level of 0.05, equal allocation, and a normal approximation. Time-to-event illustrations use total events, while other illustrations use participants per arm. The record does not report the trial’s own sample-size justification, the design assumptions used for the original study, or a planned power target.

Even a planning calculation cannot replace the observed effect and its uncertainty. Because the survival estimates and comparative effect are not reported in the registry record, the meaning of any effect-based planning illustration cannot be independently assessed from the posted results. It should not be read as evidence about whether the treatment groups differed.

10. Multiplicity, Missing Data and Analysis Populations

The record lists overall survival as the primary outcome and names objective response rate, duration of response, time to tumor progression, and time to treatment failure as secondary outcomes. It reports one analysis, but does not specify whether that is one analysis of the primary endpoint, one analysis entry in a particular registry structure, or a complete account of all statistical testing. The registry record does not report a multiplicity strategy, such as a hierarchy of hypotheses or an adjustment for testing several outcomes. Without that information, the consequences of examining multiple outcomes or analyses cannot be assessed.

Multiplicity matters because the chance of observing at least one apparently notable result can rise when many outcomes, time points, or subgroup comparisons are examined. This is a general statistical issue, not evidence that such analyses were conducted in this study. The registry does not describe planned subgroup analyses, interim analyses, or decisions about which tests would be considered confirmatory. Those details are not reported in the registry record.

The analysis population is defined for overall survival as participants randomized to study medication in the core study who consented to the extension. This is not enough to determine how missing outcome data were handled, whether all consenting participants were analyzed, or whether the analysis retained original randomized assignments. Missing-data and censoring methods are not reported in the registry record. Nor does the record describe sensitivity analyses for participants with incomplete follow-up or those who did not enter the extension.

These omissions matter for both the validity and interpretation of results. The extension population is selected by consent, and the registry cautions that the arms are not a like-for-like control comparison. Without details on participant flow, missingness, treatment exposure, and analysis, the degree to which group comparisons may be affected cannot be determined. The absence of reported methods should not be interpreted as proof that no methods were used; it means they 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 0% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: chest pain nec (2.5%), back pain (2.5%), cerebral haemorrhage (2.5%), headache nos (2.5%), spinal cord compression (2.5%).

The registry lists one participant with a serious adverse event in the exemestane group and two in the megestrol acetate group. The recorded numbers at risk for these serious-event entries are 41 and 40, respectively. It also lists other adverse events for 24 participants in the exemestane group and 25 in the megestrol acetate group, with the same group-specific numbers at risk. These are the registry’s recorded counts; they do not establish that the groups had comparable follow-up or exposure.

The serious-event terms listed include chest pain NEC, back pain, cerebral haemorrhage, headache NOS, spinal cord compression, and completed suicide. The registry gives 2.5% for each of the first five terms and 2.4% for completed suicide, but does not specify in this record which group each term belongs to or provide the event-level details needed to interpret the percentages. The terms should not be read as a complete account of all safety events.

Death counts for the safety entries are not reported in the registry record. The definitions used for serious adverse events and other adverse events, the observation period for safety reporting, and the handling of multiple events in one participant are also not reported. These figures describe recorded safety entries; they do not establish that a treatment caused an event, and they should not be used alone to compare overall safety between the groups.

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

The record documents a follow-up study of participants in an earlier comparison of exemestane and megestrol acetate. It specifies overall survival as the primary endpoint, defines the time origin and event, identifies the intended assessment schedule, and gives the population definition for the primary outcome. This information clarifies what the study set out to describe.

It does not provide the primary survival estimates or their 95% confidence intervals. The registry also does not report deaths, survival curves, a hazard ratio, or another comparative survival estimate. Consequently, the posted results do not show how long participants survived in either group, how much uncertainty surrounds those outcomes, or whether a group contrast was small or large. The absence of these results cannot be interpreted as evidence of no difference, nor as evidence of benefit or harm.

The record’s warning about the follow-up groups is especially important. The original core study is described as randomized, but the extension’s allocation is not stated, and the record cautions that the groups are not a like-for-like control comparison. The primary population includes those who consented to extension participation. Without information about selection, treatment received after the core study, or statistical adjustment, a difference between groups would not automatically represent a causal treatment effect.

The safety counts offer limited descriptive information: the record lists serious adverse events and other adverse events by group. It does not provide enough detail to determine event timing, attribution, completeness, or comparative risk. These counts should not be taken as a comprehensive safety comparison.

In short, the registry supports an account of the study context and outcome definitions, but not a conclusion about whether exemestane or megestrol acetate produced better survival or a different safety profile. Such conclusions require outcome estimates, uncertainty measures, and analysis details that are not reported in the registry record. The appropriate statistical reading is to distinguish a clearly stated question from results that are not available in the record.

13. Why This Trial Matters Statistically

This record illustrates why a study’s design label and outcome definition are only part of a statistical assessment. The original protocol is described as randomized, but the extension record explicitly says that allocation is not stated and that the arms are not a like-for-like control comparison. Recognizing the difference between the core trial and its follow-up prevents the randomized label from being carried forward without evidence.

It also highlights the importance of defining the analysis population. The primary outcome applies to participants randomized in the core study who consented to extension participation. That definition makes the boundary of the reported population clear, while also raising questions about selection into follow-up. The registry does not report who did not consent or whether their characteristics differed. In long-term follow-up, the population observed years later may not fully represent the original randomized groups.

Overall survival is a well-defined time-to-event endpoint, but its interpretation depends on more than the endpoint name. Medians and confidence intervals, event information, censoring, and analysis methods are needed to understand the estimate and its precision. In this record, those primary results are not reported. The distinction between outcome metadata and outcome findings is therefore essential: a registered endpoint is not itself evidence about the outcome.

The record also shows why safety counts require context. Group-specific counts can describe recorded events, but interpretation depends on definitions, time at risk, completeness, and event attribution. The available entries do not answer those questions. More broadly, the record demonstrates that transparency about what is and is not reported is a necessary part of statistical interpretation, especially for follow-up comparisons where group comparability may be uncertain.

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.

Several limitations specific to this record restrict interpretation. First, the primary outcome results are not reported in the registry record. Although overall survival is defined and the intended assessment schedule is stated, there are no median estimates, 95% confidence intervals, death counts, survival curves, or comparative effect estimates. The size and precision of any survival contrast therefore cannot be assessed.

Second, the extension does not report its allocation process. The record itself warns that the arms are not a like-for-like control comparison. The original protocol’s randomized design does not establish that group assignment or treatment exposure in the follow-up remained comparable. Details about treatment continuation, switching, and post-core treatment are not reported.

Third, entry into the primary analysis population required consent to extension participation. The record does not describe the number or characteristics of people who did not consent, so selection into follow-up cannot be evaluated. It also does not report the completeness of follow-up, censoring, missing-data handling, or sensitivity analyses. These gaps are relevant to long-term survival estimates.

Fourth, the secondary outcomes are named but their definitions and results are not reported. The statistical plan, multiplicity approach, subgroup analyses, interim analyses, and sample-size justification are also not reported in the registry record. The safety entries lack event definitions, attribution, timing, and group-specific details for the listed serious-event terms. These limitations prevent a detailed appraisal of both efficacy comparisons and safety patterns.

These are limitations of the information recorded, not proof that the investigators did not collect or analyze additional information. They mean that the registry record alone does not permit a full assessment of the study’s statistical methods or its treatment comparisons.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Multicenter Follow Up Study Of Subjects Who Participated In An Original Protocol Of Exemestane Vs. Megestrol Acetate In Postmenopausal Women With Metastatic Breast Cancer — NCT01237327.
• Registry record last updated 2011-05-06; status last verified 2011-05.
• Results first posted 2011-03-14.
• 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

This completed multicenter follow-up record concerns participants from an earlier study of exemestane versus megestrol acetate in postmenopausal women with metastatic breast cancer after progression on anti-estrogen treatment, with or without chemotherapy. The record identifies the core study as open-label, randomized, parallel-group, and phase III, while cautioning that allocation in the follow-up is not stated and the extension arms are not a like-for-like control comparison. Recorded enrollment is 84.

Overall survival is the primary outcome, measured from the start of core-study treatment to death from any cause, with assessment every 12 weeks up to 6 years. The median estimates and 95% confidence intervals are not reported in the registry record. Secondary outcomes include response and time-to-event measures, but their results are not reported. The record lists serious and other adverse event counts by group, with important details about event definitions and follow-up not reported.