This page provides an independent statistical analysis and educational interpretation of publicly reported results. ClinicalTrials.gov provides the official trial registry record. Numerical trial results on this page are restricted to the results posted in the ClinicalTrials.gov record; calculations added by Clinical Biostats are labelled as such.
1. Trial at a Glance
This page covers the registry results for Efficacy and Safety of BEZ235 Compared to Everolimus in Patients With Advanced Pancreatic Neuroendocrine Tumors (NCT01628913), a randomized phase 2 study. The primary outcome is Progression Free Survival (PFS).
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT01628913 |
| Phase | Phase 2 |
| Condition | Pancreatic Neuroendocrine Tumors (pNET) |
| Allocation | Randomized |
| Design model | Single Group |
| Masking | None (open label) |
| Enrollment | 62 |
| Arms in the primary outcome | 2 |
| Lead sponsor | Novartis Pharmaceuticals |
| Results posted | Yes |
2. Clinical Question
Population
Patients with advanced, low to intermediate grade pancreatic neuroendocrine tumors were eligible for this study. The primary outcome population was the full analysis set, defined as all patients randomized to study treatment and analyzed according to their randomized treatment and strata. The registry record reports 62 enrolled participants overall.
Intervention
One randomized group received BEZ235, listed as 400 mg by mouth twice daily. The study was open label, so treatment assignment was not masked.
Comparator
The other randomized group received everolimus, listed as 10 mg by mouth daily. Each group included 31 participants in the posted primary outcome results.
Primary question
The primary endpoint was progression-free survival, measured as the time from randomization until radiologically documented disease progression or death from any cause. The posted median was 8.2 months for BEZ235, with a reported lower 95% confidence limit of 5.3 months; for everolimus, the median was 10.8 months, with a reported lower limit of 8.1 months. The upper confidence limits and a sponsor-reported comparative estimate are not reported in the registry record.
3. Trial Design
The registry describes a randomized phase II study comparing BEZ235 with everolimus in advanced pancreatic neuroendocrine tumors. It is also described as multicenter and open label. Randomization assigned participants to one of the two study treatments, and treatment assignment was not masked. The posted primary outcome results list 31 participants in each group, matching the overall enrollment of 62.
The treatment regimens listed were BEZ235 400 mg by mouth twice daily and everolimus 10 mg by mouth daily. The primary outcome was progression-free survival, with a stated timeframe of up to approximately 18 months. The registry describes follow-up for the duration of the study and an expected average follow-up interval of every 12 weeks after randomization. The record does not report the reason the study was terminated.
The study also lists objective response rate, overall survival, and time to treatment failure as secondary outcomes. The registry record lists four outcome measures and zero posted analyses. That distinction matters: the presence of an outcome in the study record does not by itself establish that numerical results or a statistical comparison were posted for it.
The record identifies the full analysis set as all randomized participants, analyzed according to their assigned treatment and randomization strata, consistent with an intent-to-treat principle. Although the registry describes a randomized comparison and gives results for two treatment groups, its analysis-model classification is listed as single group. That classification sits alongside, rather than replacing, the explicit description of randomization and the two-arm outcome results. Additional details explaining the classification are not reported in the registry record.
4. Participant Flow and Accounting
The registry reports how participants moved through each stage of the study. All counts below are exactly as posted; missing counts are not inferred from other stages.
Before assignment: Patients were assigned to one of the following 2 treatment arms in a ratio of 1:1: BEZ235 (investigational arm) or everolimus (control arm)
Overall Study
| Stage | BEZ235 | Everolimus |
|---|---|---|
| STARTED | 31 | 31 |
| COMPLETED | 0 | 0 |
| NOT COMPLETED | 31 | 31 |
Reasons for not completing this period:
| Reason | BEZ235 | Everolimus |
|---|---|---|
| Adverse Event | 12 | 5 |
| Disease Progression | 11 | 14 |
| Protocol Violation | 1 | 0 |
| Death | 1 | 0 |
| study terminated by Sponsor | 4 | 9 |
| Withdrawal by Subject | 1 | 0 |
| Physician Decision | 1 | 3 |
Analysis population for the primary outcome, as defined in the registry: Full analysis set: The Full analysis set (FAS) comprised all patients who were randomized to study treatment. According to the intent to treat principle, patient was analyzed according to the treatment and strata they had been assigned to during the randomization procedure.
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.
| Characteristic | Unit | BEZ235 | Everolimus | Total |
|---|---|---|---|---|
| Participants analysed | 31 | 31 | 62 | |
| Age, Continuous | Years | 56.3 (SD 12.43) | 57.8 (SD 11.85) | 57.1 (SD 12.07) |
| Sex: Female, Male: Female | Participants | 14 | 16 | 30 |
| Sex: Female, Male: Male | Participants | 17 | 15 | 32 |
6. Primary Endpoint
The registry lists the primary outcome as Progression Free Survival (PFS), measured over up to approx. 18 months.
| Element | Registry entry |
|---|---|
| Result type | Median |
| Measure of spread | 95% Confidence Interval |
| Unit | Months |
| Endpoint classification | Time-to-Event Analysis |
Progression-free survival (PFS) measures the time from randomization until the first radiologically documented disease progression or death from any cause. In this study, progression was defined using RECIST v1.0: a 20% increase in the sum of the longest diameters of target lesions, unequivocal progression of non-target lesions, or appearance of new lesions. The assessment was based on local investigator review.
PFS is a time-to-event outcome. It accounts for both how long participants remain free of the defined event and the timing of events during follow-up. Reporting a median gives the time by which half of the observed survival distribution has experienced the event, as estimated by the study analysis. It does not describe every participant’s experience or, by itself, quantify the difference between randomized treatments.
The registry reports median PFS of 8.2 months for BEZ235 and 10.8 months for everolimus. It gives lower 95% confidence limits of 5.3 months and 8.1 months, respectively, but does not report the upper limits. A confidence interval expresses uncertainty around an estimate under the analysis assumptions; the missing upper limits make the posted interval information incomplete. A comparative hazard ratio, confidence interval for a treatment contrast, and p-value are not reported in the registry record.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The posted primary outcome results give median PFS estimates of 8.2 months for BEZ235 and 10.8 months for everolimus. The respective reported lower 95% confidence limits are 5.3 months and 8.1 months. The upper confidence limits are not reported. These values describe the estimated time-to-event distributions in the two randomized groups, but the medians alone do not establish the size or statistical uncertainty of a treatment contrast.
A randomized comparison is ordinarily interpreted using an estimate that directly contrasts the groups, together with its uncertainty and the analysis method. No sponsor-reported comparative estimate or test is posted among the listed analyses. The registry record therefore does not report a hazard ratio, its confidence interval, or a p-value for PFS. It is not possible to determine from the posted results whether the observed medians were statistically distinguishable under the sponsor’s analysis. Nor should a comparison be inferred simply by reading the two median values side by side.
The confidence intervals are also incomplete in the posted record. A lower limit alone does not show the full range of uncertainty for either median. In particular, the upper limit cannot be reconstructed from the lower limit and point estimate. The reported medians and lower limits should be quoted as posted rather than treated as complete interval estimates.
The study was randomized, and each arm’s primary-outcome population is reported as 31 participants. The endpoint definition includes death from any cause as an event as well as radiologically documented progression, with progression assessed locally. The record does not report the number of progression events, the number censored, or details of missing endpoint observations. These details would help readers understand how much follow-up information contributed to the estimates and how censoring was handled.
The registry lists objective response rate, overall survival, and time to treatment failure as secondary outcomes, but no analyses are posted. The primary and secondary outcomes should not be treated as a complete collection of trial findings when numerical results are absent. The registry also marks the study as terminated, without reporting a reason. The available record thus supports a narrow description of the posted PFS medians and some safety counts, not a comprehensive assessment of efficacy, safety, or the reasons for termination.
9. Statistical Methods Explained
Progression-free survival is a time-to-event endpoint: each participant contributes a time from randomization until an event or the end of available observation. General statistical context: because participants can have different follow-up durations, time-to-event methods are designed to use the timing of events while also accounting for participants whose event has not been observed by the end of their follow-up. The registry reports medians, but does not describe the estimator or censoring rules used to produce them.
What does a median PFS represent?
In general, the median is the point in a time-to-event distribution at which the estimated proportion remaining free of the event reaches one half. It is a summary of the distribution, not a statement that every participant experiences the event at that time. The posted medians are 8.2 months for BEZ235 and 10.8 months for everolimus. These are separate group estimates; they are not themselves a direct estimate of the relative treatment effect.
The endpoint event combines radiologically documented progression and death due to any cause. Progression was defined by RECIST v1.0 criteria, including a 20% increase in the sum of the longest diameter of target lesions, unequivocal progression of non-target lesions, or new lesions. Local investigators assessed progression. Since the event can arise from progression or death, PFS is not identical to a measure of tumor response alone. The registry does not report separate counts for progression and death within the PFS endpoint.
How should the confidence limits be read?
A confidence interval is a measure of statistical uncertainty around an estimate under a specified analysis and its assumptions. It is not a guarantee that the true value lies within the interval. The record labels the dispersion as a 95% confidence interval and provides a lower limit for each arm: 5.3 months for BEZ235 and 8.1 months for everolimus. It does not report either upper limit. Consequently, the full interval cannot be assessed from the posted figures, and no missing limit should be inferred or calculated from the median.
General statistical context: a group-specific confidence interval is not a substitute for a confidence interval around a between-group contrast. Overlap or non-overlap between separate group intervals is not a formal test of the randomized comparison. A comparative estimate, such as a hazard ratio with its confidence interval, would address a different question. Such a sponsor-reported comparison is not reported in the registry record. The record’s analysis count is zero, so no sponsor-reported PFS analysis or test is available there.
What does randomization contribute?
Random allocation is intended to make treatment groups comparable, on average, with respect to factors known and unknown at baseline. It supports a causal comparison when the analysis preserves randomized assignment and the conduct and follow-up are adequately handled. The registry states that the full analysis set included all randomized participants and that they were analyzed according to assigned treatment and randomization strata. This is described as following the intent-to-treat principle. The results list 31 participants per arm.
Randomization does not by itself resolve every uncertainty. The record does not describe the randomization procedure, allocation concealment, stratification factors, adherence, treatment discontinuation, or the handling of missing outcome information. It identifies an open-label study, meaning assignment was not masked. The endpoint was based on local investigator assessment; the registry does not report whether independent review was also conducted. These features are relevant context for interpreting a radiological outcome, but their effects cannot be quantified from the posted information.
What can be said about planning?
General statistical context: power calculations are planning tools that depend on assumptions about the treatment effect, event process, significance level, allocation, and analysis. They are not evidence that an observed result has a particular probability of being correct. The record describes an illustrative sample-size approach based on the observed effect, two-sided significance level 0.05, equal allocation, and a normal approximation; time-to-event illustrations use a total number of events. These are planning illustrations, not observed power and not the trial’s own design justification. The trial’s sample-size justification and prespecified statistical plan are not reported in the registry record. No numerical planning results are reported in the registry record.
The registry says the sponsor’s reported hazard ratios are the basis for time-to-event interpretation, but no hazard ratio value is posted among the results described. No recalculated comparative analysis is available to replace that missing sponsor analysis. The posted group medians should therefore be read descriptively, with their incomplete uncertainty limits, rather than as a complete comparative inference.
10. Multiplicity, Missing Data and Analysis Populations
The registry lists the primary outcome as PFS and names objective response rate, overall survival, and time to treatment failure as secondary outcomes. It reports four outcome measures overall, but lists zero analyses. Numerical analyses for the secondary outcomes are not reported in the registry record. A multiplicity strategy addressing the interpretation of several outcomes is not reported in the registry record.
Multiplicity matters generally when several outcomes or statistical tests are considered, because interpreting each test separately can increase the chance of a false-positive finding across the set. The record does not state whether any adjustment, hierarchy, or other prespecified approach was used. Without posted analyses and a reported plan, the role of secondary outcomes in confirmatory inference cannot be assessed.
The registry defines the full analysis set as all randomized participants, analyzed according to assigned treatment and randomization strata. This is an intent-to-treat approach. The primary outcome result lists 31 participants in each arm, but the record does not report how many participants had complete PFS follow-up, how many were censored, or how missing information was handled. The reason for any unavailable endpoint data is also not reported in the registry record.
General statistical context: censoring is not the same as observing that an event did not occur. A censored participant contributes follow-up information up to the last time their event status is known, subject to assumptions of the analysis. Missing-data methods and censoring assumptions can affect time-to-event estimates, but the details needed to evaluate them are not reported. Interim analyses, stopping rules, and the statistical plan are not reported in the registry record. The study is listed as terminated, and the reason is not reported.
11. Safety Results
The registry reports serious adverse events as affected participants divided by participants at risk.
| Arm | Participants with serious adverse events | Participants at risk | Percentage |
|---|---|---|---|
| BEZ235 | 11 | 31 | 35.5% |
| Everolimus | 9 | 31 | 29.0% |
Other (non-serious) adverse events
Participants with at least one non-serious event at or above the registry's 5% reporting threshold.
| Arm | Participants affected of at risk |
|---|---|
| BEZ235 | 31 of 31 |
| Everolimus | 30 of 31 |
Most frequent serious adverse event terms
| Event term | Organ system | BEZ235 | Everolimus |
|---|---|---|---|
| Diarrhoea | Gastrointestinal disorders | 3 of 31 | 0 of 31 |
| Ascites | Gastrointestinal disorders | 2 of 31 | 0 of 31 |
| Vomiting | Gastrointestinal disorders | 2 of 31 | 0 of 31 |
| Sepsis | Infections and infestations | 0 of 31 | 2 of 31 |
| Dyspnoea | Respiratory, thoracic and mediastinal disorders | 1 of 31 | 1 of 31 |
| Thrombocytopenia | Blood and lymphatic system disorders | 0 of 31 | 1 of 31 |
| Cardiac failure congestive | Cardiac disorders | 0 of 31 | 1 of 31 |
| Adrenal insufficiency | Endocrine disorders | 1 of 31 | 0 of 31 |
| Cushing's syndrome | Endocrine disorders | 0 of 31 | 1 of 31 |
| Abdominal pain | Gastrointestinal disorders | 1 of 31 | 0 of 31 |
Most frequent non-serious adverse event terms
| Event term | Organ system | BEZ235 | Everolimus |
|---|---|---|---|
| Diarrhoea | Gastrointestinal disorders | 28 of 31 | 17 of 31 |
| Stomatitis | Gastrointestinal disorders | 23 of 31 | 20 of 31 |
| Nausea | Gastrointestinal disorders | 17 of 31 | 10 of 31 |
| Asthenia | General disorders | 13 of 31 | 13 of 31 |
| Rash | Skin and subcutaneous tissue disorders | 11 of 31 | 13 of 31 |
| Decreased appetite | Metabolism and nutrition disorders | 9 of 31 | 13 of 31 |
| Vomiting | Gastrointestinal disorders | 14 of 31 | 7 of 31 |
| Abdominal pain | Gastrointestinal disorders | 12 of 31 | 8 of 31 |
| Hyperglycaemia | Metabolism and nutrition disorders | 9 of 31 | 11 of 31 |
| Anaemia | Blood and lymphatic system disorders | 8 of 31 | 11 of 31 |
Serious events with the highest arm-level rate: diarrhoea (9.7%), ascites (6.5%), vomiting (6.5%), sepsis (6.5%), thrombocytopenia (3.2%).
The posted safety figures use 31 participants at risk in each treatment group. Serious adverse events affected 11 participants in the BEZ235 group and 9 in the everolimus group. The record also reports other adverse events affecting 31 participants in the BEZ235 group and 30 in the everolimus group. These are participant counts, not counts of all event episodes; a participant may experience more than one event.
The serious adverse event terms listed most prominently are diarrhoea (9.7%), ascites (6.5%), vomiting (6.5%), sepsis (6.5%), thrombocytopenia (3.2%), and cardiac failure congestive (3.2%). These percentages are reported as posted. The list does not provide a complete account of all events or their severity, timing, duration, or relationship to treatment. Death counts are not reported in the registry record.
General statistical context: adverse-event counts describe what was recorded during study observation; they do not by themselves establish that a treatment caused an event. Differences in follow-up, exposure, event definitions, and reporting can affect comparisons. The registry does not report exposure duration or a comparative safety analysis. The figures should therefore be read as descriptive counts and listed terms, not as a formal estimate of relative risk or a causal conclusion.
12. What the Result Does, and Does Not, Mean
The record supports a descriptive statement about the posted primary outcome: median PFS was 8.2 months in the BEZ235 group and 10.8 months in the everolimus group. The lower reported 95% confidence limits were 5.3 months and 8.1 months, respectively. The upper limits are not reported. These estimates come from randomized groups of 31 participants each and use a PFS definition that includes radiological progression or death from any cause.
The record does not provide a sponsor-reported hazard ratio, confidence interval for the treatment contrast, or p-value. Without a direct comparative analysis and complete uncertainty information, the medians cannot establish whether the groups differed statistically or quantify the precision of a treatment contrast. The posted estimates also do not establish a causal conclusion beyond what can be supported by the design and reported analyses.
The record identifies three secondary outcomes—objective response rate, overall survival, and time to treatment failure—but does not post their analyses. It reports some adverse-event counts and serious-event terms, but not a complete safety analysis, treatment exposure, or death counts. It also lists the study as terminated without giving a reason. These omissions limit interpretation of the overall benefit-risk profile and the study’s completion.
General statistical context: a result’s meaning depends on how the endpoint was defined, how participants were followed, how missing observations and censoring were handled, and what analysis was prespecified. Those details are incomplete or not reported in the registry record. The estimates should therefore be understood as the specific outcome values posted, with incomplete interval reporting and without a posted between-group inference. They do not, on their own, establish that either treatment works or does not work.
13. Why This Trial Matters Statistically
This trial is statistically informative as an example of the distinction between a randomized design and a fully reported comparative result. The record describes random assignment to BEZ235 or everolimus and defines an intent-to-treat full analysis set. It also posts median PFS for both groups. Yet a randomized comparison is not fully interpretable from group-specific medians alone: the comparative estimate and its uncertainty are needed to assess the contrast directly.
The record’s partial confidence intervals illustrate another reporting issue. A lower limit is available for each median, but neither upper limit is reported. Readers cannot reconstruct complete intervals from the posted values. This makes it especially important not to treat the displayed point estimates as precise descriptions of the full time-to-event distributions.
The study also highlights the difference between a planned or listed outcome and an analyzed result. Several secondary outcomes are named, while the registry lists zero analyses. Listing an outcome establishes that it was part of the registry record, but does not provide the findings or analysis needed to interpret it. Likewise, sample-size planning illustrations are not evidence of achieved power or a substitute for the trial’s design justification.
Finally, the open-label design and local investigator assessment are relevant features of outcome measurement. They do not by themselves determine the direction or magnitude of bias, and the record does not provide enough information to quantify such effects. Clear reporting of the analysis method, missingness, censoring, and comparative estimates would be needed for a more complete statistical reading.
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 primary outcome information is incomplete for evaluating the treatment contrast. Median PFS is reported for each arm, along with a lower confidence limit, but upper limits are not reported. The registry record does not report a sponsor-reported hazard ratio, comparative confidence interval, or p-value. It also lists zero analyses, leaving no posted formal comparison to interpret.
The record does not report the number of PFS events, censoring details, missing endpoint observations, or methods for handling missing data. It identifies local investigator assessment and a RECIST v1.0 progression definition, but does not report whether any additional independent assessment was used. The planned sample-size justification and statistical analysis plan are not reported in the registry record, nor are interim analyses or stopping rules.
The study is marked terminated, but the reason is not reported. The registry identifies secondary outcomes but does not post analyses for them. Safety information is limited to participant counts, selected serious-event terms, and other adverse-event counts; exposure duration, deaths, and a comparative safety analysis are not reported. Finally, the analysis-model classification is listed as single group despite the randomized two-arm study description and posted two-arm results; the registry does not explain this classification.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Efficacy and Safety of BEZ235 Compared to Everolimus in Patients With Advanced Pancreatic Neuroendocrine Tumors — NCT01628913.
- Registry record last updated 2016-04-07; status last verified 2016-03.
- Results first posted 2016-04-07.
- 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.
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18. Record Summary
This is a randomized, open-label, phase II study of BEZ235 versus everolimus in advanced pancreatic neuroendocrine tumors. The record reports 62 participants enrolled, with 31 listed in each arm for the primary outcome. The study is marked terminated; the reason is not reported.
The primary endpoint was PFS, defined from randomization to radiologically documented progression or death from any cause and assessed locally. Median PFS was 8.2 months for BEZ235 and 10.8 months for everolimus. Lower 95% confidence limits were 5.3 months and 8.1 months; upper limits and a sponsor-reported comparative analysis are not reported.
Secondary outcomes include objective response rate, overall survival, and time to treatment failure, with no analyses posted. Serious adverse events affected 11 of 31 participants receiving BEZ235 and 9 of 31 receiving everolimus. Further details needed for a complete comparative interpretation are not reported in the registry record.