Everolimus Combined With Anti-estrogen Therapy in Hormone-Receptor-Positive HER-2 Negative Advanced Breast Cancer: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Everolimus Combined With Anti-estrogen Therapy in Hormone-Receptor-Positive HER-2 Negative Advanced Breast Cancer (NCT02291913), a na phase 2 study. The primary outcome is Median Progression Free Survival (PFS).

2. Clinical Question

The clinical question is whether progression-free survival and other outcomes can be described for participants receiving everolimus with an anti-estrogen regimen after prior progression on anti-estrogen therapy. Because the study has no randomized comparator, it cannot estimate a treatment contrast against a concurrent control group. Its primary endpoint is a time-to-event measure within the treated group, rather than a direct comparison of outcomes between assigned groups.

The study also lists objective response, clinical benefit, duration of response, overall survival, and adverse events as outcomes. These measures address different aspects of the clinical course: tumor response, sustained disease control, time until progression or death after response, survival, and safety. Their definitions and results are not all reported in the registry record. The record therefore supports a description of the question and planned outcome domains, but not a complete account of the observed efficacy results.

3. Trial Design

This was a completed Phase II, open-label, single-group study sponsored by SCRI Development Innovations, LLC. The registry lists an enrollment of 48. The study started on 2014-12-18, reached primary completion on 2019-01-31, and has a status of COMPLETED. Allocation is recorded as NA, and masking is recorded as NONE.

Participants received everolimus in combination with an anti-estrogen therapy. The arm description states that everolimus was administered at 10 mg PO daily, with the anti-estrogen therapy on which the patient had most recently progressed. The listed agents include tamoxifen, fulvestrant, anastrozole, letrozole, exemestane, and toremifine, and the description also mentions LHRH agonists in conjunction with anti-estrogen therapy. The registry record does not give further detail on how treatment selection was made.

The absence of a randomized comparator is central to interpreting this design. Outcomes can be described among participants receiving the study regimen, but the design does not support a randomized estimate of how outcomes differ from those under another treatment. Open-label status means masking is not listed; the registry record does not describe additional procedures intended to limit knowledge of treatment assignment.

The primary outcome was median progression-free survival, with a timeframe of up to 3 years. The outcome description defines the event and censoring rules. Per the registry record, 36 of the 48 patients were analyzed for PFS because they received at least 1 cycle of study treatment and had at least one post-baseline radiologic assessment. The remaining 12 treated patients did not meet that criterion. The registry record does not report the rationale for the sample size, the statistical analysis plan, or 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:

Analysis population for the primary outcome, as defined in the registry: Participants who received at least 1 cycle of study treatment and had at least one post-baseline radiologic assessment were evaluable for PFS analysis per protocol. 36 of the total 48 patients were analyzed for PFS. The remaining 12 treated patients did not meet this criteria to be analyzed.

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: All patients who received at least one dose of treatment.

6. Primary Endpoint

The registry lists the primary outcome as Median Progression Free Survival (PFS), measured over up to 3 years.

Progression-free survival (PFS) is the time from Day 1 of study drug administration to disease progression, as defined by RECIST version 1.1 criteria, or death on study. The registry lists median PFS as the primary endpoint, with a 95% confidence interval and a timeframe of up to 3 years. The median is a summary of the time-to-event distribution: it marks the point by which half of the relevant event-time distribution has occurred, when it can be estimated.

The endpoint uses both disease progression and death as events. According to the outcome description, participants alive and free from progression are censored at the date of their last radiologic tumor assessment. Participants who start non-protocol subsequent therapy before an event are censored at their last tumor assessment before that therapy. Participants without a post-baseline tumor assessment are censored at Day 1.

General: time-to-event endpoints can incorporate information from participants whose event has not been observed by their last assessment, by recording their follow-up as censored rather than treating them as if an event occurred. The interpretation depends on the event definition, follow-up, and censoring rules. The registry record gives these rules but does not report the median PFS or its confidence interval, so the observed primary endpoint cannot be quantified from the record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

General: a time-to-event analysis follows participants from a defined starting point until an event occurs or follow-up ends. In this study, the starting point is Day 1 of study drug administration. The event is disease progression under RECIST version 1.1 criteria or death on study. This definition determines which events count toward PFS; it should not be confused with other endpoints such as objective response or overall survival.

What does the median represent?

General: the median time-to-event estimate describes the middle of the event-time distribution. Unlike a simple average, it does not require every participant to experience the event during observation. A confidence interval expresses uncertainty around an estimate under the statistical method used. A narrower interval generally indicates greater precision, while a wider interval indicates less precision. The registry names a 95% confidence interval for median PFS, but does not report its limits or the median itself.

How is censoring used?

General: censoring records that an event time is not observed during the available follow-up, while retaining information up to the last relevant observation. The PFS description specifies several censoring situations. Participants alive and without progression are censored at their last radiologic tumor assessment. Participants who begin subsequent, non-protocol therapy before an event are censored at the last tumor assessment before that therapy. Participants with no post-baseline tumor assessment are censored at Day 1. These rules define how follow-up contributes to the endpoint; they do not reveal how many participants were censored or when censoring occurred.

General: censoring is not equivalent to observing that a participant remained event-free indefinitely. Interpretation relies on the recorded follow-up and on assumptions about how censoring relates to the chance of the event. The registry outcome description states the rules, but does not report diagnostic checks or additional details about these assumptions.

What does the analysis population tell us?

The record states that participants needed at least 1 cycle of treatment and at least one post-baseline radiologic assessment to be evaluable for the PFS analysis. It reports that 36 of the 48 patients were analyzed and that the remaining 12 treated patients did not meet the criterion. General: defining an analysis population affects which participants contribute to an estimate. Excluding participants without a post-baseline assessment can limit how fully the result represents all treated participants, particularly if missing assessments are related to prognosis or treatment experience. The registry record does not describe the outcomes of these 12 participants or a sensitivity analysis addressing their exclusion.

Why does the design matter?

The study is classified as single-group, with allocation NA and no masking. General: an estimate from a single group describes outcomes in that group, while random assignment to a comparator can help distinguish treatment effects from other differences between groups. Without a randomized comparator, any observed PFS cannot by itself establish what would have happened to the same participants under another treatment. The registry record does not report a separate control arm or a comparative treatment estimate.

What can be inferred from the reported methods?

The outcome description provides the endpoint definition, timeframe, and censoring rules, and the record names the median and 95% confidence interval as the primary summary. However, it does not report the statistical model or estimation procedure used, the PFS result, the confidence interval, or a hazard ratio. General: a hazard ratio is a relative comparison of event rates over follow-up when a suitable comparison is available and its assumptions are appropriate. No sponsor-reported hazard ratio is reported in the registry record, and the single-group design supplies no randomized contrast.

The registry record also does not report a statistical analysis plan or sample-size justification. A planning illustration based on an observed effect is not a description of the trial’s original design rationale and is not observed power. General: power is a design concept concerning the chance of detecting a specified effect under stated assumptions; it is not a measure of whether a completed study’s observed result is true. The record’s sample-size assumptions describe an illustrative calculation, not evidence that the original trial was designed using those assumptions.

Finally, the record lists several secondary outcomes, but an outcome name does not specify its analysis in full. The registry does not report the statistical methods used for each secondary endpoint, adjustment for multiple testing, or how missing observations were handled for those outcomes. Those omissions limit the ability to reconstruct or assess the complete analysis from the registry record.

10. Multiplicity, Missing Data and Analysis Populations

The registry lists a primary outcome and several secondary outcome domains: adverse events, objective response, clinical benefit, duration of response, and overall survival. The record does not report a multiplicity strategy or explain how statistical interpretation was to account for examining multiple outcomes. General: when several outcomes are tested, the chance of at least one apparently notable result can increase, depending on the testing approach and relationships among outcomes. A prespecified hierarchy or adjustment can address some of this concern, but neither is reported in the registry record.

The record also does not report an analysis plan, planned interim analyses, or a sample-size justification. These items cannot be inferred from the Phase II label, completion status, or enrollment. No analysis count is reported in the registry data, and there is no reported sponsor analysis that can be compared with an unadjusted recalculation.

For PFS, the record gives an analysis-population rule requiring at least 1 cycle of study treatment and at least one post-baseline radiologic assessment. It reports that 36 of 48 patients met the stated criterion, while the remaining 12 treated patients did not. The registry record does not report the reasons each participant failed to meet it, their subsequent outcome information, or analyses that include them in another way.

The PFS censoring rules are stated, but the record does not report the amount or timing of censoring. It also does not describe missing-data methods for the secondary outcomes. General: missing observations can affect estimates when participants with unavailable data differ systematically from those with complete follow-up. Without further detail, the direction or size of any such effect cannot be determined. These gaps mean that the analysis populations, missingness, and multiplicity cannot be fully evaluated from the registry record.

11. Safety Results

The registry reports serious adverse events as affected participants divided by participants at risk.

Deaths

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: constipation (4.2%), anemia (2.1%), cardiac failure congestive (2.1%), esophagitis (2.1%), gastrointestinal hemorrhage (2.1%).

The registry lists 48 participants at risk for the Everolimus group, 15 affected by serious adverse events, 48 affected by other adverse events, and 32 deaths. These are distinct record entries and should not be treated as interchangeable measures. The registry record does not establish that the deaths or adverse events were caused by study treatment. A count of affected participants also does not describe event severity, duration, recurrence, or timing by itself.

The serious adverse-event terms with listed percentages are constipation at 4.2%, anemia at 2.1%, cardiac failure congestive at 2.1%, esophagitis at 2.1%, gastrointestinal hemorrhage at 2.1%, and non-cardiac chest pain at 2.1%. These percentages are reported as serious-event figures; the registry record does not provide further detail about event timing, individual participants, or attribution. They should not be interpreted as estimates of comparative risk because there is no randomized control group.

General: safety counts describe observed events in the population and follow-up recorded, and their interpretation depends on how events were collected, classified, and attributed. The registry record does not report additional detail on those procedures or a full account of all event categories. The listed figures therefore characterize the registry’s posted safety information, not a treatment comparison or a causal conclusion.

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

The record documents a completed Phase II study of everolimus combined with anti-estrogen therapy in advanced hormone-receptor-positive, HER2-negative breast cancer. It describes a primary PFS endpoint, its event definition, and rules for censoring. It also identifies secondary outcome areas and gives selected safety information. These details clarify what the study set out to measure and how the primary endpoint was defined.

The registry does not report the median PFS or its 95% confidence interval. Without those values, it is not possible to describe the observed primary outcome’s magnitude or precision. The record also does not report the listed secondary efficacy results in a way that supports a complete numerical interpretation. A study’s completion and its enrollment do not fill in these missing results.

The single-group, open-label design supports a descriptive account of outcomes among participants receiving the regimen. It does not provide a randomized comparison with another treatment, and therefore cannot isolate the effect of everolimus plus anti-estrogen therapy from other explanations for observed outcomes. The data should not be read as proving that the regimen does or does not alter disease outcomes.

The safety entries provide counts and selected serious-event terms, but do not establish treatment causation or comparative safety. The record also leaves important analytical details unreported, including the statistical analysis plan, multiplicity approach, and fuller information about missing outcomes and censoring. Those limitations affect how much can be concluded from the registry record, independently of the study’s completed status.

13. Why This Trial Matters Statistically

This trial is statistically informative in part because it makes the distinction between an outcome definition and an outcome result visible. The registry specifies PFS as time from Day 1 of study drug administration to progression under RECIST version 1.1 criteria or death on study, and it lists a median with a 95% confidence interval as the summary. Yet the median and interval are not reported in the registry record. A clearly described endpoint does not substitute for the estimate needed to judge its magnitude and precision.

The analysis-population description is also important. Although enrollment was 48, the record says that 36 participants were analyzed for PFS under a criterion requiring treatment and a post-baseline radiologic assessment. The other 12 treated participants did not meet that criterion. This distinction helps readers understand which participants contribute to the reported analysis, while also highlighting the need for information about excluded participants and missing follow-up.

The single-group design demonstrates why design and analysis must be considered together. Even a well-defined time-to-event outcome would describe outcomes in the treated group, not a randomized treatment contrast. Without a concurrent randomized comparator, causal interpretation is limited. The record’s safety figures likewise describe observed events rather than comparative risks.

Finally, the registry does not report a statistical analysis plan, a sample-size justification, an interim-analysis approach, or a multiplicity strategy. Their absence means readers cannot reconstruct those parts of the study’s statistical framework. The record is therefore useful for understanding the registered question, endpoint definition, analysis population, and design constraints, while leaving the main numerical efficacy result unavailable.

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 most direct limitation of the registry record is that it names median PFS as the primary endpoint but does not report the median or its 95% confidence interval. The primary result’s magnitude and precision therefore cannot be assessed. The record also does not give a sponsor-reported hazard ratio or a complete set of numerical results for the listed secondary efficacy outcomes.

The PFS analysis population was 36 of the 48 enrolled patients. The other 12 treated patients did not meet the stated eligibility criterion for PFS analysis, which required at least 1 cycle of treatment and at least one post-baseline radiologic assessment. The registry record does not describe why each participant failed to meet the criterion, their clinical follow-up, or sensitivity analyses for their exclusion.

The single-group, open-label design has no randomized comparator, so estimates within the treated group cannot establish a treatment contrast. The registry record also does not report the complete eligibility criteria, details of treatment selection, statistical analysis plan, sample-size justification, interim analyses, multiplicity handling, or methods for missing data across secondary outcomes. The PFS censoring rules are stated, but the number and timing of censored observations are not reported.

The safety information is limited to registry figures and selected serious-event terms. The record does not provide further detail about event timing, attribution, or comparative safety. These limitations concern the information available in the registry record; they do not establish what was or was not reported elsewhere.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Everolimus Combined With Anti-estrogen Therapy in Hormone-Receptor-Positive HER-2 Negative Advanced Breast Cancer — NCT02291913.
• Registry record last updated 2020-02-17; status last verified 2020-02.
• Results first posted 2020-02-17.
• 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

NCT02291913 is a completed, open-label Phase II, single-group study sponsored by SCRI Development Innovations, LLC. It enrolled 48 participants and evaluated everolimus combined with anti-estrogen therapy in advanced hormone-receptor-positive, HER2-negative breast cancer. The registry lists the primary endpoint as median PFS, with a 95% confidence interval and a timeframe of up to 3 years. PFS was defined from Day 1 of study drug administration to progression under RECIST version 1.1 criteria or death on study.

The registry reports that 36 participants were analyzed for PFS under the stated assessment criterion; 12 treated participants did not meet it. It does not report the median PFS, its confidence interval, a sponsor-reported hazard ratio, or complete numerical results for the listed secondary efficacy outcomes. The record includes selected safety figures and serious-event terms. Because there is no randomized comparator, the study describes outcomes in a single treated group rather than a randomized treatment contrast.