Study to Assess the Efficacy and Safety of Lanreotide Autogel® in Chinese Participants With GEP-NETs: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Study to Assess the Efficacy and Safety of Lanreotide Autogel® in Chinese Participants With GEP-NETs (NCT04852679), a na phase 3 study. The primary outcome is Clinical Benefit Rate (CBR) of Tumour Response Assessed by Blinded Independent Central Review (BICR) at Week 24.

2. Clinical Question

This question concerns the proportion meeting a specified tumour-response category at an assessment time, rather than a comparison of treatment strategies. Complete response, partial response, and stable disease have distinct RECIST v1.1 definitions in the registry record. The composite clinical benefit rate combines these categories, so its interpretation depends on the stated response criteria and the Week 24 assessment.

The record also lists secondary outcomes, including progression-free survival, overall survival, time to progression, response and disease-control rates, and NET-related clinical symptoms. Their presence indicates the range of outcomes planned or registered, but their numerical results and analysis details are not reported in the registry record. No causal treatment effect can be estimated from a single-group study without a suitable comparator.

3. Trial Design

This was a Phase 3, single-arm, open-label, multicentre study sponsored by Ipsen. It enrolled 43 participants and is marked completed in the registry. The listed study dates are 2021-05-24 for study start and 2022-06-10 for primary completion. The participants were Chinese and had unresectable, locally advanced or metastatic Grade 1 or 2 GEP-NETs.

The intervention was lanreotide Autogel 120 mg, administered by deep subcutaneous injection every 28 days, with the arm description allowing a window of plus or minus 3 days. The brief summary describes a screening period of up to 4 weeks followed by a 48-week intervention period. It also describes a self/partner injection cohort after the main study period: five participants were to continue treatment every 28 days for 24 weeks. The adverse-event record labels this later interval the independent injection period.

There was no randomized allocation and no masking. The primary endpoint was clinical benefit rate (CBR) assessed by blinded independent central review at Week 24. The endpoint description specifies baseline assessment within 28 days before intervention and a Week 24 assessment. Although the study was open-label, central review is described as blinded; the registry record does not report further details of that review process.

The record describes the primary analysis population as the intention-to-treat set, defined as participants who received at least 1 dose of study intervention. It does not report how many enrolled participants met that definition or how many had evaluable Week 24 assessments. The study has no like-for-like control arm, so its design supports description of outcomes in the treated group but does not isolate a treatment effect from other explanations. Details of the protocol’s sample-size justification, statistical plan, and interim analyses 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: This study consisted of a screening period (up to 4 weeks), followed by a 48-week main intervention period and then a 24-week independent injection period. A total of 43 participants were treated in this study.

Main Intervention Period

Reasons for not completing this period:

Independent Injection Period

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: The ITT analysis set included all participants who received at least 1 dose of study intervention.

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: The Intention-To-Treat (ITT) analysis set included all participants who received at least 1 dose of study intervention.

6. Primary Endpoint

The registry lists the primary outcome as Clinical Benefit Rate (CBR) of Tumour Response Assessed by Blinded Independent Central Review (BICR) at Week 24, measured over RECIST assessments performed at baseline (within 28 days before start of study intervention) and Weeks 24.

The primary endpoint is the percentage of participants with a best overall response of confirmed complete response, confirmed partial response, or continued stable disease by Week 24, assessed using RECIST v1.1 and reviewed by a blinded independent central review. Complete response means disappearance of all target lesions. Partial response requires at least a 30% decrease in the sum of the longest diameters of target lesions relative to the baseline sum. Stable disease means neither enough shrinkage to meet partial response nor enough increase to meet progressive disease, using the smallest sum since treatment started as the reference.

Combining these three categories into CBR gives a binary summary: each participant either meets the endpoint definition or does not. This can be useful when the clinical question concerns the proportion with tumour response or continued stability at a defined assessment, rather than the magnitude of change for each participant. The endpoint relies on the response criteria, timing of imaging, confirmation rules, and availability of assessments. The registry record gives the endpoint definition and assessment timing but does not report the observed CBR, its confidence interval, or how missing Week 24 assessments were handled.

Because the study has no concurrent control group, the endpoint is descriptive of the participants assessed under this study. It does not by itself quantify what would have happened to comparable participants under another treatment or no study intervention.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The primary outcome is a binary participant-level classification: the endpoint is met if the participant’s best overall response falls into one of the specified categories by the assessment time, and it is not met otherwise. The registry reports the outcome as a percentage of participants and specifies a 95% confidence interval as the dispersion measure. The observed percentage and interval are not reported in the registry record, so no estimate or precision assessment can be reconstructed from the record.

What does a confidence interval communicate?

In general, a confidence interval gives a range of values compatible with the observed data under the statistical model and its assumptions. For a proportion, the interval communicates uncertainty due to sampling variability. A wider interval indicates less precision than a narrower one, although interval width is also affected by the method used to calculate it. A confidence interval is not a guarantee that the true value lies within that particular interval, and it does not account for every source of bias. In this study, the registry record does not state the interval calculation method or report the interval itself.

Why does the response definition matter?

The endpoint combines confirmed complete response, confirmed partial response, and continued stable disease according to RECIST v1.1. Complete response is defined by disappearance of target lesions; partial response requires at least a 30% decrease in the sum of target-lesion longest diameters from baseline; stable disease requires neither sufficient shrinkage for partial response nor sufficient increase for progressive disease, with the smallest sum since treatment began as reference. These rules make the outcome more reproducible than an unspecified judgement of improvement. They also mean that the composite depends on lesion measurement, assessment timing, confirmation, and the classification of each participant. The registry record does not provide component-level results or further operational details.

What does central review contribute?

The primary assessment is described as being made by blinded independent central review. In general, central review can apply a common assessment process across participating sites, while blinding can reduce the influence of knowledge about treatment assignment on outcome classification. Here, the study has one treatment group and is open-label, but the record describes the central review as blinded. Details such as what information reviewers were blinded to and how disagreements were resolved are not reported in the registry record. Central review does not eliminate measurement error or create a randomized comparator.

How should the single-group design be read?

In general, a single-group study estimates outcomes among participants receiving the study intervention. Without a concurrent comparison group, it cannot separate an intervention effect from natural disease course, participant selection, changes in care, or other influences. The registry lists allocation as not applicable and the study model as single group. Thus, any outcome percentage would be descriptive of the enrolled and analysed group, subject to the analysis population and missing-data handling. The registry record does not report a statistical plan for adjusting or otherwise accounting for prognostic factors.

What can the planning illustration mean?

General sample-size calculations use assumptions about the target effect, error rates, allocation, and statistical method to estimate how much information a future study might need. The planning assumptions associated with this record describe a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. The effect to detect is expressed as a stated fraction of the observed effect. These are planning illustrations, not observed power. They do not describe the actual single-arm allocation in this trial, and the registry record does not report a protocol sample-size justification. Sample-size outputs should be understood as hypothetical planning quantities rather than as outcomes or evidence that the study was adequately powered.

The record notes that planning illustrations for time-to-event outcomes use a total number of events, while other illustrations use participants per arm. Generally, time-to-event calculations are often driven by the number of outcome events, whereas calculations for a binary outcome may be expressed as participants per group. Neither type of planning calculation changes the fact that this study has one group. Numerical planning outputs and the effect estimate on which they depend are not reported in the registry record.

Why can over-dispersion matter?

In general, over-dispersion occurs when observed variability exceeds what a model assumes. If a model underestimates variability, its standard errors may be too small and its confidence intervals too narrow. Different outcomes require different models, and over-dispersion is especially relevant to some count-data models. The primary CBR outcome is a proportion, and the registry record does not report the model or variance method used. It would therefore be inappropriate to assert that over-dispersion was assessed or to infer its impact in this study.

For time-to-event outcomes such as progression-free survival, overall survival, and time to progression, general analyses account for both the time to an event and censoring, when a participant’s event time is not observed during follow-up. Interpretation depends on the event definition, follow-up, censoring rules, and analysis method. Those details and numerical results are not reported in the registry record. A method cannot be inferred solely from the outcome name.

10. Exact Estimates for Each Arm

No two-arm comparison is shown for this trial, but each arm's result can still be summarized with exact interval estimates computed from the posted counts. The Clopper-Pearson interval is exact and conservative; the Wilson interval is a common closer-to-nominal alternative; the Bayesian credible interval uses a uniform Beta(1, 1) prior. For small groups the three can differ noticeably.

R code and output

arm    <- c("Lanreotide Autogel 120 mg")
n      <- c(43)
events <- c(27)
for (i in seq_along(n)) {
  ci <- binom.test(events[i], n[i])$conf.int          # Clopper-Pearson exact interval
  cr <- qbeta(c(0.025, 0.975), 1 + events[i], 1 + n[i] - events[i])   # Bayesian, uniform Beta(1,1) prior
  wi <- (function(x, n) { p <- x / n; z <- qnorm(0.975); d <- 1 + z^2 / n
    c((p + z^2 / (2 * n) - z * sqrt(p * (1 - p) / n + z^2 / (4 * n^2))) / d, (p + z^2 / (2 * n) + z * sqrt(p * (1 - p) / n + z^2 / (4 * n^2))) / d) })(events[i], n[i])
  cat(sprintf("ARM|%s|%d|%d|%.1f|%.1f|%.1f|%.1f|%.1f|%.1f|%.1f\n", arm[i], n[i], events[i], 100 * events[i] / n[i],
              100 * ci[1], 100 * ci[2], 100 * wi[1], 100 * wi[2], 100 * cr[1], 100 * cr[2]))
}

ARM  Lanreotide Autogel 120 mg  43  27  62.8  46.7  77.0  47.9  75.6  47.8  75.6

11. Multiplicity, Missing Data and Analysis Populations

The registry lists multiple secondary outcomes in addition to the primary CBR endpoint. These include progression-free survival, overall survival, time to progression, proportions alive without tumour progression at Weeks 24 and 48, clinical benefit rate at Week 48, overall response and disease-control rates at Weeks 24 and 48, and NET-related clinical symptoms. When many outcomes or assessment times are examined, the chance of at least one apparently notable finding can increase. General approaches to multiplicity include prespecifying a hierarchy, adjusting significance thresholds, or treating secondary analyses as exploratory. The registry record does not report whether any such strategy was used, so no adjustment procedure should be assumed.

The record defines the primary analysis set as participants who received at least 1 dose of study intervention. It does not report the number in that set, the number with an available Week 24 assessment, or whether the same analysis population was used for each secondary outcome. Although the endpoint is expressed as a percentage of participants, the handling of missing or unevaluable assessments is not reported in the registry record. In general, excluding participants with missing outcome data can affect a proportion if missingness is related to response; alternative methods also depend on assumptions that should be described explicitly.

The record does not report the statistical analysis plan, interim analyses, imputation methods, sensitivity analyses, or rules for censoring time-to-event outcomes. It also does not state how participants with incomplete follow-up were handled for survival outcomes. These omissions prevent assessment of whether analyses followed prespecified rules or how robust the results would be to alternative assumptions. The absence of reported details does not establish that a particular method was or was not used; it means the registry record does not describe it.

12. 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: diarrhoea (2.3%), ileus (2.3%), oesophageal varices haemorrhage (2.3%), alanine aminotransferase increased (2.3%), aspartate aminotransferase increased (2.3%).

During the main intervention period, 4 participants were recorded with serious adverse events among 43 at risk, and 2 deaths were recorded. During the independent injection period, no participants were recorded with serious adverse events among 5 at risk, and no deaths were recorded. The registry also reports other adverse events for 43 participants at risk in the main period and 2 participants at risk in the independent injection period.

The listed serious adverse-event terms each have a reported frequency of 2.3%: diarrhoea, ileus, oesophageal varices haemorrhage, alanine aminotransferase increased, aspartate aminotransferase increased, and hypokalaemia. These are registry-reported event frequencies; the record does not provide enough detail to determine overlap between terms or whether individual participants experienced more than one event. No causal attribution should be inferred from the counts alone.

The periods differ in the number of participants at risk, so their raw counts are not a direct like-for-like comparison. The registry record does not report exposure-adjusted rates, event timing, severity breakdowns, or a control group. These safety figures are descriptive of recorded events in each period and do not establish comparative risk.

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

The study record describes an investigation of lanreotide Autogel 120 mg in Chinese participants with unresectable, locally advanced or metastatic Grade 1 or 2 GEP-NETs. Its primary endpoint is a Week 24 CBR assessed by blinded independent central review using RECIST v1.1. The record specifies what qualifies as complete response, partial response, or stable disease and defines the primary analysis population as participants who received at least 1 dose.

However, the registry record does not report the numerical primary endpoint result, the number meeting the endpoint, or the confidence interval. It therefore does not show how frequently participants met the registered CBR definition or how precise an estimate might be. The endpoint description alone is not evidence of a particular response level. The record also lists secondary outcomes, but their numerical results and analysis details are not reported.

The single-arm, open-label design has no concurrent randomized comparator. As a result, outcomes observed in the study cannot be used to estimate a causal difference between lanreotide and another treatment or no treatment. A descriptive outcome, even if reported, would reflect the participants, follow-up, assessments, and analysis rules used in this study. Blinded central review may standardize response assessment, but it does not address the absence of a control group.

The safety record provides counts of serious adverse events and deaths across the main and independent injection periods, along with selected serious-event terms. Those counts describe recorded events, not proof that treatment caused or prevented them. The different periods have different numbers of participants at risk, and no comparative safety estimate is reported.

Accordingly, the registry supports understanding the study design, registered endpoint, and selected safety counts. It does not support a numerical conclusion about the primary efficacy result, its precision, or a comparative treatment effect. Missing analysis details also limit evaluation of multiplicity, missing outcomes, and the methods used for secondary endpoints.

14. Why This Trial Matters Statistically

This study is statistically notable for the contrast between a clearly defined response endpoint and the absence of its numerical result in the registry record. The endpoint definition specifies the RECIST categories, the Week 24 assessment, and independent central review. Those details help establish what the study intended to measure, but they cannot substitute for the observed estimate, participant counts, or confidence interval. Without those results, readers cannot assess the magnitude or precision of the primary outcome.

The single-arm design also matters. It can describe outcomes in the studied group, but it does not provide a randomized estimate of how outcomes differ under another treatment strategy. This distinction is important when interpreting response rates: a proportion in one group is not itself a comparative effect. The open-label design and central review feature should be understood separately. Central review is described as blinded, but that does not turn the study into a blinded or controlled comparison.

The study also illustrates why registered endpoints and reported analyses are different kinds of information. Several secondary outcomes are listed, spanning response, progression, survival, and symptoms. Without their results and analysis details, their listing cannot establish findings. Missing-data rules, multiplicity handling, and methods for time-to-event outcomes are not reported in the registry record, limiting assessment of how those outcomes would be interpreted.

Finally, planning illustrations are distinct from observed trial evidence. The associated assumptions describe hypothetical two-arm calculations, while this study is a single-group trial. Such planning quantities are not observed power and do not show that the trial detected an effect. Separating design, analysis assumptions, observed results, and causal interpretation is essential for an accurate statistical reading of the record.

15. 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 affect interpretation. The principal limitation is that the registry record does not report the numerical Week 24 CBR result, its confidence interval, or the count of participants meeting the endpoint. As a result, the primary outcome cannot be evaluated for magnitude or precision using the record alone.

The trial is single-arm and has no concurrent comparator. Its findings, if reported, would describe outcomes in the study group and would not by themselves establish a causal treatment effect. The study is also open-label, although the primary response assessment is described as blinded independent central review. The record does not explain the practical blinding procedures or disagreement resolution.

The analysis population is defined as participants who received at least 1 dose, but the record does not report how many participants were included in that set or how many had evaluable assessments. The approach to missing or unevaluable Week 24 assessments is not reported. Nor are the statistical analysis plan, multiplicity strategy, sensitivity analyses, or methods for secondary time-to-event outcomes reported in the registry record.

The listed safety counts are descriptive and span periods with different numbers at risk. The record does not provide comparative safety data, exposure-adjusted event rates, or detailed event timing. It also does not clarify overlap among the listed serious-event terms. These limitations constrain interpretation of both efficacy and safety and should not be filled in by assumptions about methods or outcomes not described in the record.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Study to Assess the Efficacy and Safety of Lanreotide Autogel® in Chinese Participants With GEP-NETs — NCT04852679.
• Registry record last updated 2024-10-01; status last verified 2024-06.
• Results first posted 2024-10-01.
• 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.

19. Record Summary

NCT04852679 is a completed Phase 3, open-label, multicentre, single-group study of lanreotide Autogel 120 mg in Chinese participants with unresectable, locally advanced or metastatic Grade 1 or 2 GEP-NETs. The study enrolled 43 participants and used injections every 28 days. Its main intervention period was 48 weeks, with a later independent injection period described for five participants.

The primary endpoint was Week 24 CBR by blinded independent central review using RECIST v1.1. The registry record defines the endpoint and the analysis population but does not report the observed CBR or its confidence interval. It lists several secondary outcomes without reporting their numerical results or analysis details. Safety entries include serious adverse events and deaths for the main and independent injection periods. The single-arm design does not provide a randomized comparison, and statistical details on missing data, multiplicity, and analysis methods are not reported in the registry record.