Efficacy and Safety of Lanreotide Autogel (ATG) in Combination With Temozolomide in Subjects With Thoracic Neuroendocrine Tumors.: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Efficacy and Safety of Lanreotide Autogel (ATG) in Combination With Temozolomide in Subjects With Thoracic Neuroendocrine Tumors. (NCT02698410), a na phase 2 study. The primary outcome is Disease Control Rate (DCR) Assessed Locally at Month 9.

2. Clinical Question

3. Trial Design

This was a Phase II, multicentre, single-arm, open-label trial of lanreotide ATG in combination with temozolomide. The registry record lists enrollment of 40 participants and a completed status. Because there was no randomized allocation and no comparator group, the design describes outcomes among participants receiving the combination rather than estimating a treatment contrast against a concurrent control.

Lanreotide ATG 120 mg was administered by deep subcutaneous injection every 28 days for a maximum of 48 weeks, corresponding to a maximum of 12 injections. Temozolomide 250 mg hard capsules were taken orally for five consecutive days every 28 days, also for a maximum of 48 weeks. The record names the intervention as lanreotide in its Autogel formulation combined with temozolomide.

The primary outcome was locally assessed disease control at Month 9. The registry also lists secondary outcomes concerning disease control at Month 9 and Month 12, progression-free survival, time to response, duration of response, time to progression, best overall response, and objective response rate. Some outcomes were assessed locally and centrally. The registry record lists 16 outcome measures and 6 analyses, but the statistical details of those analyses are not reported in the registry record.

The study was open-label, so participants and investigators were not masked to treatment. The record does not report a comparator, allocation procedure, or a protocol-based rationale for the planned enrollment. It also does not report the recruitment or follow-up procedures in the information available for this analysis. These design features matter when interpreting outcomes: a single-group study can describe observed disease control and safety, but without a control group it cannot separate treatment-associated outcomes from the course that might have occurred without the combination.

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: The study consisted of a screening period (maximum 4 weeks), followed by an open label treatment period of up to a maximum of 52 weeks or until disease progression, death or unacceptable toxicity, or subject/physician decision.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: The ITT/Safety population included all participants who received at least 1 dose of study medication (either lanreotide ATG 120 mg or temozolomide).

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)/Safety population included all participants who received at least 1 dose of study medication (either lanreotide ATG 120 mg or temozolomide).

6. Primary Endpoint

The registry lists the primary outcome as Disease Control Rate (DCR) Assessed Locally at Month 9, measured over Up to Month 9; for sensitivity analysis-2, up to 10.5 months.

The primary endpoint was the percentage of participants with disease control assessed locally at Month 9. Under the stated RECIST version 1.1 definition, disease control included complete response, partial response, or stable disease. Participants with progressive disease did not meet this definition. The endpoint therefore classifies tumor response at a specified assessment time rather than measuring the length of time until progression or response.

A disease control rate is a binary outcome at the participant level: each participant either meets the disease-control definition or does not, according to the assessment and analysis rules. Reporting a percentage makes the result interpretable as the proportion of the analyzed population meeting the endpoint. A confidence interval communicates statistical uncertainty around that estimated proportion; it does not remove uncertainty or establish that the result would be the same in another population.

The registry record describes sensitivity analyses with different handling of participants withdrawn before Month 9 and assessments near the Month 9 time point. Those rules are important because endpoint classification can depend on whether a participant has an assessment at the planned time. The primary endpoint result itself is not reported in the registry record, so its estimated rate and confidence interval cannot be described.

This endpoint is used to capture participants whose disease is either responding or not progressing at the specified assessment. It is distinct from progression-free survival, which concerns time to an event, and from objective response rate, which does not include stable disease in its response definition.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The primary outcome is a binary participant-level endpoint. A participant is classified as having disease control if the local investigator’s RECIST version 1.1 assessment is complete response, partial response, or stable disease. Otherwise, the participant does not meet the endpoint definition. The disease control rate is the proportion classified as having disease control among the participants included under the analysis rules. The registry record identifies the outcome unit as a percentage of participants, but does not report the observed percentage.

What the confidence interval conveys

The registry record specifies a 95% confidence interval for the primary endpoint. In general, a confidence interval expresses the statistical uncertainty around an estimate under the method used to construct it. A narrower interval indicates greater precision than a wider interval, all else equal. It does not mean that the underlying value is known exactly, and it does not address whether the study population or assessment process is representative of other settings. The interval limits and the calculation method are not reported in the registry record.

Why the single-group design matters

This is a single-group trial, not a randomized comparison. In general, a single-group estimate describes outcomes observed among the participants receiving the intervention. It cannot directly distinguish an intervention-associated outcome from what might have occurred in the absence of that intervention. Randomization is one way to balance measured and unmeasured prognostic factors between groups, but this trial has no second group for such a contrast. The registry record does not report a comparative efficacy estimate.

Assessment timing and sensitivity analyses

The primary time point is Month 9, but the registry description recognizes that participants may lack an assessment at that time. It describes one sensitivity analysis excluding participants withdrawn before Month 9 for reasons other than progressive disease or a missing assessment, while treating progressive disease by Month 9 as failure. A second sensitivity analysis allowed assessments between 7.5 and 10.5 months to serve as Month 9 assessments when the Month 9 assessment was missing. Under the described approach, participants with progressive disease by Month 9 and participants withdrawn for other or missing reasons were treated as failures.

Sensitivity analyses examine whether conclusions depend on analytic choices. Agreement across reasonable approaches can support robustness, while differences can show that the estimate is sensitive to how missing or off-time assessments are handled. The registry describes these rules, but does not report the resulting estimates, so their effect on the endpoint result is unknown.

Over-dispersion and binary outcomes

For a binary outcome, the observed proportion is subject to sampling variability. General statistical methods may use assumptions about how participant outcomes vary around an underlying probability. Over-dispersion means that variability is greater than a model’s basic assumptions would predict. When present, methods that account for it can produce more realistic uncertainty estimates. The registry record does not report whether an over-dispersion adjustment was considered or used; no such method should be inferred from the endpoint definition alone.

Time-to-event outcomes

The registry lists progression-free survival, time to response, duration of response, and time to progression among secondary outcomes. In general, time-to-event analyses use both the timing of an event and information from participants whose event time is not observed during follow-up. Such participants may be censored, meaning that their observed follow-up contributes information up to a point without asserting that the event never occurs. The registry record names these outcomes but does not report their estimates, censoring rules, or analysis methods.

Planning illustrations are not observed power

Sample-size calculations based on an observed effect can be used as planning illustrations for a future study. They ask how many participants might be needed under specified assumptions to detect an effect of a chosen size. Such calculations do not measure the probability that the completed trial detected a true effect, and they do not replace a trial’s original design justification. The registry record does not report the protocol’s sample-size justification or statistical plan. Any planning illustration should therefore be read as conditional on its stated assumptions, not as a reported feature of the trial’s original design.

10. Multiplicity, Missing Data and Analysis Populations

The registry record lists multiple secondary outcomes and reports 16 outcome measures and 6 analyses. When a study examines several outcomes or conducts several analyses, the chance of obtaining at least one apparently notable result can increase. In general, multiplicity procedures can control error across a defined family of tests, while a prespecified hierarchy can determine which results are confirmatory and which are exploratory. The registry record does not report whether a multiplicity adjustment, hierarchy, or other approach to multiple testing was planned or used.

Missing outcome assessments are especially relevant to a time-specific binary endpoint. The registry describes sensitivity analyses for participants withdrawn before Month 9 and for missing Month 9 assessments, including use of assessments in a specified nearby time window in one analysis. It also describes treating certain withdrawals and participants with progressive disease as failures. These definitions make explicit that missingness is handled through analysis rules rather than simply ignored. The corresponding sensitivity-analysis results are not reported in the registry record.

The primary population is described as the ITT/Safety population and includes all participants who received at least one dose of either study medication. The registry record therefore defines this population by treatment receipt, rather than by enrollment alone. It does not report further details on exclusions from outcome analyses, participant-level missingness, or whether other analysis populations were used for particular outcomes.

There is no comparator arm, so multiplicity considerations do not create a randomized treatment comparison that is otherwise absent. The statistical plan for handling multiple outcomes, missing data, and analysis populations is not reported in 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 0% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: death (2.5%), non-cardiac chest pain (2.5%), pain (2.5%), cholecystitis (2.5%), diverticulitis (2.5%).

The adverse-event summary lists 40 participants at risk in the lanreotide ATG plus temozolomide group. It reports 9 participants affected by serious adverse events and 38 affected by other adverse events. The record also reports 9 deaths. These are descriptive counts in a single treated group; without a comparator, they do not establish how the event burden compares with another treatment or with the background risk in a similar population.

The serious-event terms listed most frequently include Death, Non-cardiac chest pain, Pain, Cholecystitis, Diverticulitis, and Back pain, each reported as 2.5%. These term-specific percentages should be read as entries in the adverse-event summary, not as estimates of comparative risk. The record does not explain in the information how the reported death count relates to the Death serious-event term, so they should not be treated as interchangeable figures.

Serious adverse events are not the same as all adverse events: an event’s seriousness is a classification, not a statement about how often all symptoms or events occurred. The registry record does not report event severity grades, attribution to study medication, exposure-adjusted rates, or comparative safety estimates in the registry record for this analysis. These figures describe reported events among trial participants and do not establish causation.

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

The record establishes the trial’s question, design, intervention, and primary endpoint definition. It describes a Phase II, open-label, single-arm study of lanreotide ATG with temozolomide for progressive, well-differentiated thoracic neuroendocrine tumors. Its primary endpoint was locally assessed disease control at Month 9, with disease control defined as complete response, partial response, or stable disease under RECIST version 1.1.

The primary endpoint result is not reported in the registry record. As a result, the observed disease control rate and the precision of that estimate cannot be assessed. The record also lists secondary efficacy outcomes, but does not report their results in the information summarized for this analysis. A completed study status does not substitute for outcome estimates.

Even if the observed disease control rate were available, the single-group design would support a description of outcomes among participants who received the combination, not a randomized estimate of benefit relative to another treatment. The open-label design also means that treatment was not masked; the primary outcome was assessed locally by investigators. Central assessments are listed for some secondary outcomes, but their estimates are not reported.

The safety summary reports serious and other adverse events and deaths among participants in the treated group. These counts are descriptive. The absence of a control group and the lack of comparative safety estimates mean that the figures cannot establish whether events were caused by the treatment or whether their frequency differs from another setting.

The record does not report the protocol’s sample-size justification, full statistical plan, multiplicity approach, or detailed missing-data results. Those omissions limit assessment of how the study was originally designed to address uncertainty and how robust its conclusions were intended to be. The available information supports a careful description of the planned question and reported safety counts, but not a conclusion about efficacy or comparative safety.

13. Why This Trial Matters Statistically

This trial is statistically informative as an example of how an early-phase, single-group study frames a disease-control question. The endpoint is defined at a specific assessment time and combines complete response, partial response, and stable disease. That definition makes the clinical classification explicit, while the registry’s sensitivity-analysis descriptions show that missing or mistimed assessments can affect how participants are classified in a time-specific analysis.

The single-arm design also illustrates the distinction between estimating an outcome rate and estimating a treatment effect. A disease control rate can describe what happened among treated participants. A comparative effect requires a valid comparison, and this study has no concurrent control group. This distinction is important when interpreting percentages from uncontrolled studies: the number alone does not identify what would have happened to the same participants under a different treatment or without study treatment.

The registry record also identifies a 95% confidence interval as the primary endpoint’s dispersion measure. This highlights the need to interpret an estimate together with its precision, rather than relying on a point estimate alone. However, neither the primary estimate nor its interval is reported in the registry information. The methodological framing can therefore be discussed, but the numerical strength and precision of the study’s primary finding cannot be judged.

Finally, the record describes multiple secondary outcomes and sensitivity analyses. These features make transparent reporting of analysis rules and results important, particularly when outcomes and missing-data decisions may be examined in more than one way. The record does not report the full statistical plan or the results of those analyses. The trial therefore provides a useful case for distinguishing a clearly defined endpoint from the evidence needed to evaluate its observed result.

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 principal limitation for interpreting efficacy is that the primary disease control rate and its 95% confidence interval are not reported in the registry record. Although the endpoint definition and sensitivity-analysis rules are described, the observed result and the results of those sensitivity analyses are unavailable in the information.

The study is single-arm and open-label, with no randomized comparator. Consequently, it cannot directly estimate a contrast with another treatment or separate treatment-associated outcomes from the course of disease in the absence of the combination. Local investigator assessment is specified for the primary endpoint. The record lists centrally assessed secondary outcomes, but does not report their results.

The record lists 40 enrolled participants and defines the ITT/Safety population as participants who received at least one dose. It does not report detailed participant flow, the number included in each efficacy analysis, or the amount and pattern of missing endpoint data. The described sensitivity analyses address some missing or off-time assessments, but their estimates are not reported.

The statistical plan, sample-size justification, and approach to multiplicity are not reported in the registry record. This limits assessment of whether the analyses were prespecified and how the study addressed multiple outcomes. The adverse-event summary is also descriptive and lacks a comparator; the information does not report event attribution, severity grades, or comparative safety estimates. These limitations do not negate the endpoint definitions or the reported event counts, but they constrain the conclusions that can be drawn from them.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Efficacy and Safety of Lanreotide Autogel (ATG) in Combination With Temozolomide in Subjects With Thoracic Neuroendocrine Tumors. — NCT02698410.
• Registry record last updated 2020-10-01; status last verified 2020-09.
• Results first posted 2020-10-01.
• 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.

18. Record Summary

The registry record identifies NCT02698410 as a completed, multicentre, open-label Phase II single-group trial with enrollment of 40 participants. It studied lanreotide ATG 120 mg with temozolomide 250 mg in subjects with progressive, well-differentiated thoracic neuroendocrine tumors. Treatment was planned for a maximum of 48 weeks.

The primary endpoint was locally assessed disease control at Month 9 under RECIST version 1.1, defined as complete response, partial response, or stable disease. The primary result and its confidence interval are not reported in the registry record. Listed secondary outcomes include centrally assessed disease control and several response and time-to-event measures.

The adverse-event summary reports 9 participants affected by serious adverse events, 38 affected by other adverse events, and 9 deaths among 40 participants at risk. No comparator group is reported, so these figures are descriptive rather than comparative. The registry record does not report the full statistical plan, sample-size justification, or multiplicity approach.