Everolimus After (Chemo)Embolization for Liver Metastases From Digestive Endocrine Tumors: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Everolimus After (Chemo)Embolization for Liver Metastases From Digestive Endocrine Tumors (NCT01678664), a na phase 2 study. The primary outcome is Rate of Hepatic Progression Free Survival at 24 Months.

2. Clinical Question

3. Trial Design

The registry identifies NCT01678664 as a phase 2, completed, single-group study with an enrollment of 74. Its title concerns everolimus after embolization or chemoembolization for liver metastases from digestive endocrine tumors. The study started in 2012-12, and primary completion was recorded as 2018-09. These dates describe the registry record and do not by themselves indicate when individual participants began or completed treatment.

The treatment group combined embolization or chemoembolization with everolimus. The regimen description refers to 2 sessions of embolization using microspheres of 100 to 500 µm, or chemoembolization using 100 mg of doxorubicin and 10 ml of lipiodol. Everolimus was described as 10 mg daily for 24 months or until progression, whether hepatic or at another site. The registry lists embolization, doxorubicin, and everolimus among the interventions.

Allocation is listed as NA and masking as none. The design is identified as single-group, with no randomized control arm. The outcomes listed beyond the primary endpoint are progression-free survival, hepatic or not, and overall survival. The record lists 3 outcome measures, but the complete outcome results and analysis details are not reported in the registry record. A protocol, detailed statistical analysis plan, and explanation of the enrollment target are also not reported in the registry record.

Because every participant was assigned to the same overall treatment strategy, the design can describe outcomes observed in this treated group but cannot make a randomized comparison with an untreated or alternative-treatment group. Any interpretation of the observed outcome would need to account for this design limitation as well as the reported endpoint definition and analysis population.

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: Before enrollement, standard examinations (biological, clinical) were done. In terms of imaging, abdominal and thoracic computed tomography scan or MRI were also done.

Overall Study

Analysis population for the primary outcome, as defined in the registry: The analysis population for the primary endpoint was defined as the population of evaluable patients. A patient was considered evaluable if he or she hadreceived at least one dose of everolimus and at least one image on treatment. A patient who died (from any cause after treatment) or progressed to liver disease before 24 months was evaluable and considered a failure for the primary endpoint.

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 the patients enrolled in the study

6. Primary Endpoint

The registry lists the primary outcome as Rate of Hepatic Progression Free Survival at 24 Months, measured over Up to 24 months.

The primary endpoint is titled “Rate of Hepatic Progression Free Survival at 24 Months.” It concerns whether a participant remains alive without hepatic progression during the stated period. The endpoint description defines hepatic progression-free survival using RECIST 1.1, with death from any cause treated as progression. It describes the interval from inclusion to hepatic progression or death; for participants alive without hepatic progression, the description uses the date of the last tumor assessment.

A time-specific progression-free survival rate is useful because it expresses the proportion of the study population meeting a clinically interpretable status at a defined point, rather than describing progression alone. Including death in the event definition means that the endpoint reflects both hepatic disease progression and death, as specified in the registry. The primary question focused on the 24-month rate and compared it with the 35% threshold stated in the brief summary.

There is an important difference in the endpoint wording: the brief summary says the assessment would be central, while the detailed primary endpoint description refers to an investigator-based assessment. The registry record does not explain this difference. It also lists the primary measure as a count of participants, but does not report the observed count or rate. Thus the endpoint’s intended meaning is described, while its numerical result and the relationship between the two assessment descriptions are not reported in the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

What does a 24-month rate represent?

As a general statistical concept, a time-specific progression-free survival rate is an estimate of the proportion of a defined population that has not experienced the event by a specified time. In this trial, the event definition includes hepatic progression or death, and the specified time is 24 months. Participants who have not experienced an event need adequate follow-up to support their status at that point. When follow-up varies or ends before the target time, survival methods can use the timing of events and censoring rather than treating every participant as though they had identical observation.

The registry description says that participants alive without hepatic progression are followed to their last tumor assessment. That wording indicates the relevance of last assessment when no event has been recorded, but the record does not provide the full analysis method, censoring rules, or estimate. It also does not report how missing assessments or incomplete follow-up were handled. Those details affect how a time-specific rate should be interpreted, so they cannot be inferred from the endpoint title alone.

How does the threshold question differ from a treatment comparison?

As a general statistical concept, a single-group threshold analysis asks whether an outcome estimate is compatible with a specified benchmark or differs from it under a statistical model. The brief summary sets 35% as the boundary between its stated hypotheses and gives 50% as the expected rate. The registry record does not report a test statistic, confidence interval, p-value, or the observed rate, so no conclusion about the benchmark can be reconstructed from the posted information.

A benchmark is not a concurrent randomized control group. In a single-group study, the study population and its care are not matched through random assignment to a comparison group. Differences between this group and a historical expectation could arise for reasons other than the treatment being evaluated. As a general concept, this limits causal interpretation even when the outcome is measured carefully.

Why do the analysis population and endpoint wording matter?

The primary analysis population is described as evaluable patients, requiring at least one dose and at least one image on treatment. This is narrower than simply referring to everyone enrolled, although the registry does not give the resulting analysis count. As a general statistical concept, an analysis restricted to participants with treatment and follow-up data can differ from one that includes everyone enrolled. If the chance of being evaluable is related to prognosis or treatment experience, the estimated outcome may not represent the full enrolled group in the same way.

The endpoint description refers to investigator-based assessment, but the brief summary refers to central assessment. Assessment procedures can matter because judgments about progression determine when an event is counted. The registry does not resolve the difference or provide further detail about how assessments were reconciled. The reported endpoint should therefore be interpreted with that uncertainty in mind, rather than assuming that one wording overrides the other.

What can confidence intervals and missing analyses tell readers?

As a general concept, a confidence interval describes the uncertainty around an estimated quantity under the statistical assumptions used to construct it. A narrow interval generally indicates greater precision, while a wider interval indicates that a broader range of values remains compatible with the data and method. No confidence interval for the primary outcome is reported in the registry record. Without an estimate and interval, neither the apparent distance from the 35% threshold nor the precision of that estimate can be assessed.

The registry lists no analyses. This does not establish that no analyses were conducted; it means their results are not reported in the registry record. The statistical plan, handling of repeated or incomplete assessments, and any adjustment or sensitivity analyses are also not reported in the registry record. Statistical methods cannot safely be inferred from the endpoint label, phase, or study question.

How should the planning illustrations be read?

As a general concept, a sample-size planning illustration describes how many participants might be needed under stated assumptions to detect a specified effect with a chosen significance level and power. It is a design calculation, not an observed result and not “observed power.” The planning assumptions associated with the illustrations specify a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation; the effect is expressed as a fraction of the observed effect. Those assumptions describe hypothetical planning comparisons, not the single-group design of this trial. The illustrations should not be taken as the number enrolled, the number analyzed, or evidence that the study had a particular probability of detecting an effect. The registry record does not report the trial’s own sample-size justification.

For time-to-event outcomes, a general planning method may focus on the number of events, whereas other outcomes may use participants per arm. The planning note distinguishes those conventions. Since the present trial has one group and no randomized control comparison, a two-arm illustration is not a direct description of its actual design. None of the planning calculations can replace the missing primary endpoint estimate or its uncertainty.

10. Multiplicity, Missing Data and Analysis Populations

The registry lists a primary endpoint and secondary outcomes of progression-free survival, hepatic or not, and overall survival. It does not report a statistical analysis plan explaining how these outcomes were prioritized in analysis, whether multiple hypotheses were tested, or whether any adjustment for multiple testing was planned. When several outcomes or tests are considered, the chance of at least one apparently notable result can increase; as a general statistical concept, multiplicity procedures are sometimes used to control that issue. No particular procedure can be attributed to this trial from the registry record.

The primary population is described as evaluable patients who received at least one dose of everolimus and at least one on-treatment image. The registry record does not state how many participants met that definition. The description of the population is truncated after referring to a patient who died or progressed, so the complete analysis-population rules are not reported in the registry record. The record also does not report how missing images, withdrawals, or other incomplete follow-up were handled, or whether sensitivity analyses were conducted.

These omissions matter for a 24-month endpoint because participants may differ in how long they are observed and whether their progression status can be assessed. As a general concept, missing outcome information can affect both the denominator and the interpretation of an estimated rate, depending on why the information is missing and how the analysis treats it. No assumption about those reasons or methods should be made. With no reported endpoint result, analysis count, or missing-data approach, the robustness of the primary estimate cannot be assessed 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: general physical health deterioration (8.1%), diarrhoea (6.8%), cholecystitis (6.8%), anaemia (5.4%), cardiac failure (4.1%).

The adverse event record lists 74 participants at risk for serious adverse events and 35 affected, alongside 74 at risk for other adverse events and 67 affected. It also lists 32 deaths. These are the registry’s group-level counts; they do not by themselves establish whether an event was caused by a particular intervention. The record does not provide a comparative safety group, and a single-group count cannot isolate the contribution of everolimus from that of embolization, chemoembolization, underlying disease, or other influences.

The listed serious adverse event terms and percentages are general physical health deterioration, 8.1%; diarrhoea, 6.8%; cholecystitis, 6.8%; anaemia, 5.4%; cardiac failure, 4.1%; and vomiting, 4.1%. These percentages are reported as listed; the registry record does not give additional details about event timing, duration, severity grades, or whether participants could have experienced more than one listed event. The figures should therefore be read as adverse event reporting, not as a causal comparison or a complete account of individual risk.

The record lists deaths but does not state in this adverse event summary whether they were considered treatment-related. The cause and timing of the deaths are not reported in the registry record. No inference about attribution should be drawn from the count alone.

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

This registry record documents a phase 2, single-group study of everolimus after embolization or chemoembolization for liver metastases from digestive endocrine tumors. The stated primary question concerns hepatic progression-free survival at 24 months and whether its rate exceeds 35%. The brief summary also states an expected rate of 50%. These figures describe the study’s stated hypothesis and expectation; they are not the trial’s observed result.

The record does not report an observed primary endpoint rate, the number of participants included in the primary analysis, a confidence interval, or a statistical test. It therefore cannot show whether the stated threshold was met or how precisely an estimate was determined. The listed secondary outcomes likewise have no results reported in the registry record. The available adverse event counts and selected terms describe reported safety information but do not answer the primary efficacy question.

Even if a primary endpoint estimate were available, a single-group study would not establish what would have happened to comparable participants under a different treatment strategy. Without randomized allocation to a control group, observed outcomes cannot be attributed solely to everolimus. The sequential treatment context also includes embolization or chemoembolization, so the registry describes a combined treatment strategy rather than a randomized test of everolimus in isolation.

The endpoint wording itself requires care: the brief summary mentions central assessment, while the detailed description refers to investigator-based assessment. The record does not explain the difference. The findings, if reported elsewhere, would need to be understood in light of the assessment method, the evaluable-patient definition, and follow-up handling. The registry record alone supports conclusions about the study’s design and stated question, not about whether the regimen achieved the target outcome or caused the reported adverse events.

13. Why This Trial Matters Statistically

Statistically, this trial is a useful example of the distinction between a study question and a study result. The registry states a clear threshold-based question for hepatic progression-free survival at 24 months, but does not report the estimate needed to answer it. A prespecified hypothesis or expected rate cannot stand in for observed evidence. Readers need the actual estimate and its uncertainty to judge both its magnitude and precision.

The single-group design also highlights the difference between benchmarking and randomized comparison. A threshold can frame an exploratory question, but it does not create a concurrent control group. An observed outcome in one treated group cannot by itself determine how much of that outcome is due to the treatment strategy rather than participant characteristics, disease course, assessment, or other factors.

The record further illustrates why endpoint definitions and analysis populations belong alongside a headline outcome. The primary outcome includes hepatic progression or death, and the evaluable population requires treatment exposure and on-treatment imaging. The discrepancy between central and investigator assessment wording, the truncated population description, and the absence of the analysis denominator leave important interpretive details unresolved.

Finally, safety counts and efficacy outcomes answer different questions. Adverse event counts can describe what was reported among participants at risk, but without comparative data and attribution detail, they cannot establish causation or relative safety. Taken together, the record makes clear which design features and questions were registered while leaving the central efficacy result and several statistical analysis details unreported.

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 central limitation is that the registry record does not report the primary endpoint result. No observed 24-month hepatic progression-free survival rate, analysis denominator, uncertainty interval, or test result is listed. As a result, the threshold question that motivated the study cannot be answered from the posted registry information.

The single-group design has no concurrent randomized comparison, so any observed outcome would not isolate the effect of everolimus from the effects of the preceding embolization or chemoembolization and other factors. The record also gives no detailed eligibility criteria or complete account of participant characteristics. The number enrolled is reported as 74, but the number evaluable for the primary outcome is not reported in the registry record.

There is a discrepancy in how the primary outcome assessment is described: the brief summary refers to central assessment, while the detailed endpoint description refers to investigator assessment. The registry does not explain which assessment governed the primary analysis. The evaluable-population description is incomplete, and the rules for missing or incomplete imaging and follow-up are not reported in the registry record.

The registry lists secondary outcomes but does not report their results, and it does not report a statistical analysis plan, multiplicity approach, sample-size justification, or analysis methods beyond the endpoint definition. The adverse event record gives group counts and selected serious-event terms, but does not supply event timing, attribution, or a comparative safety group. These limitations restrict both efficacy interpretation and causal interpretation of safety findings.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Everolimus After (Chemo)Embolization for Liver Metastases From Digestive Endocrine Tumors — NCT01678664.
• Registry record last updated 2024-09-25; status last verified 2024-09.
• Results first posted 2024-09-25.
• 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

NCT01678664 is recorded as a completed phase 2, single-group study with enrollment of 74. It evaluated everolimus after embolization or chemoembolization for liver metastases from digestive endocrine tumors. The regimen description specifies everolimus 10 mg daily for 24 months or until progression, following 2 sessions of embolization or chemoembolization.

The primary endpoint was hepatic progression-free survival at 24 months, defined in the detailed description as hepatic progression or death, with RECIST 1.1 cited. The brief summary states a threshold of 35% and an expected rate of 50%. The registry record does not report the observed primary outcome result or its uncertainty. It lists overall survival and progression-free survival, hepatic or not, as secondary outcomes, without reported results. Adverse event counts and selected serious-event terms are listed, but no randomized control group is described.