Trial of Pevonedistat Plus Docetaxel in Patients With Previously Treated Advanced Non-Small Cell Lung Cancer: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Trial of Pevonedistat Plus Docetaxel in Patients With Previously Treated Advanced Non-Small Cell Lung Cancer (NCT03228186), a na phase 2 study. The primary outcome is The Percentage of Patients That Respond to Treatment.

2. Clinical Question

In statistical terms, the primary question is descriptive: among the participants considered evaluable for this endpoint, what proportion met the registry's response definition? A single-group result can describe outcomes in the treated cohort, but it does not directly estimate how those outcomes differ from what would have happened under another treatment or no treatment. Without a comparison group, the trial cannot isolate the contribution of either drug or of the combination.

The study is identified as a Phase II trial and was described as a single institution study. Its stated focus is the efficacy of the combination in patients with previously treated advanced non-small cell lung cancer. The registry record lists secondary outcomes including median progression-free survival time, median overall survival time, stable disease, and toxicities by system organ class. Results for those outcomes are not reported in the registry record.

3. Trial Design

NCT03228186 is listed as a Phase II, single-group trial of pevonedistat plus docetaxel in patients with previously treated advanced non-small cell lung cancer. The registry record identifies no allocation scheme and no masking. Its brief description calls the study a single institution, single arm trial. There is no separate control arm listed, so the design supports description of outcomes in the treated group rather than a randomized comparison between treatments.

The listed regimen was pevonedistat 25mg/m2 on days 1, 3, and 5 and docetaxel 75mg/m2 on day 1, in a 21 day cycle. The primary outcome is the percentage of patients who respond, assessed over up to 2 years. Response includes partial response or complete response, according to the criteria described in the registry record. Secondary outcomes include median progression-free survival time, median overall survival time, the number of patients who achieve stable disease, and the number of toxicities by system organ class.

The registry record lists enrollment of 40 and says 27 patients participated long enough to be considered evaluable for the primary outcome. These figures refer to different descriptions of the study population; the reason for the difference, and further participant flow details, are not reported in the registry record. The study status is terminated. The reason for termination is not reported in the registry record.

The listed start date is 2018-03-05, and the primary completion date is 2021-11-04. A more detailed account of the protocol, including the sample-size justification, planned interim analyses, and the complete statistical analysis plan, is not reported in the registry record. Those omissions limit how closely a reader can assess whether the posted outcome data follow the intended analysis plan.

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: 9 patients screen failed

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: 27 patients participated in the trial long enough to be considered evaluable for this outcome measure

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: 9 patients were screen failed

6. Primary Endpoint

The registry lists the primary outcome as The Percentage of Patients That Respond to Treatment, measured over Up to 2 Years.

The primary outcome is the percentage of patients who respond to treatment, with response defined as either partial response or complete response. The registry description defines partial response as at least a 30% decrease in the sum of the longest diameter of target lesions, using the baseline sum as the reference, with no new lesions. Complete response requires disappearance of all target lesions, confirmed by two separate observations conducted not less than 4 weeks apart, with no new lesions. The stated timeframe is up to 2 years.

As a general statistical concept, a response percentage gives a concise summary of how often a predefined outcome occurred in a study group. It is clinically interpretable because the endpoint translates lesion measurements into a category defined by the protocol. The definition also matters: different response criteria or assessment schedules could classify the same patient differently.

The record identifies 27 patients as evaluable for this outcome. However, it does not report how many met the response criteria, the resulting percentage, or the stated 85% confidence interval. The endpoint definition and evaluable population can therefore be described, but the observed response result cannot be assessed from the registry record. Details of imaging assessment, independent review, handling of unevaluable cases, and the analysis used to construct the interval are not reported in the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The primary outcome is binary at the participant level: each evaluable patient either meets the response definition or does not. The registry reports the outcome in percentage terms and describes an 85% confidence interval. It does not report the response count, percentage, interval limits, or the statistical method used to calculate the interval. The method and any analysis details are not reported in the registry record.

What does a response percentage estimate?

As a general statistical explanation, a response percentage estimates the proportion of a defined study population who meet the stated response criteria during the specified assessment period. Its meaning depends on both the criteria and the population included in the calculation. Here, the registry identifies 27 patients as evaluable for the primary outcome and defines response as partial or complete response. The record does not give the numerator, so the observed percentage cannot be reconstructed or interpreted.

The distinction between a percentage and a count is useful. The count states how many participants met the outcome; the percentage expresses that count relative to the analyzed population. Both are needed to understand the estimate. The registry's primary outcome description gives the unit as percent of participants, but does not provide either the response count or the observed percentage. No alternative calculation should be inferred from enrollment or evaluability figures alone.

What does the confidence interval add?

As a general statistical explanation, a confidence interval describes uncertainty around an estimated quantity under a particular statistical procedure. It is not a guarantee that the true value lies within the interval, and it does not account for every possible source of bias. Its interpretation depends on the procedure and the analysis population. The record specifies an 85% confidence interval but does not give its limits or calculation method. It is therefore not possible to assess the precision of the response estimate or verify the interval from the registry record.

The interval's confidence level is not the probability that the treatment is effective or that an individual patient will respond. Rather, confidence intervals are properties of statistical procedures applied to data. This is general statistical interpretation; the registry record does not describe how the interval was produced or how it was intended to guide decisions.

Why does the single-group design matter?

As a general statistical explanation, an outcome observed in a single group describes that group under the study conditions. Without a comparator, it does not directly estimate a contrast between the regimen and another option. A response percentage in this design cannot separate the effects of pevonedistat and docetaxel from one another, or from other influences on the observed outcome. The record lists no randomized comparator and no allocation scheme.

Randomization, when used, can help balance measured and unmeasured factors between groups in expectation. That general benefit does not apply as a treatment comparison in this single-group record. The registry does not report a control group, matching strategy, or other comparative analysis. No causal treatment effect should be inferred from the primary response endpoint alone.

How should the response definition be read?

The registry's partial-response definition requires at least a 30% decrease in the sum of the longest diameter of target lesions relative to baseline and no new lesions. Complete response requires disappearance of all target lesions, confirmed by two observations at least 4 weeks apart, with no new lesions. These rules create a prespecified classification framework, but details about how scans were scheduled, interpreted, or independently reviewed are not reported in the registry record.

As a general statistical point, clear outcome criteria improve consistency by making the classification rule explicit. Still, measurement procedures, timing, and missing assessments can affect which participants are classified as responders. The registry description does not provide enough information to evaluate those operational details.

What analysis details are absent?

The registry record lists no analyses. It does not report a statistical analysis plan, the confidence-interval method, handling of unevaluable patients, missing-data procedures, or whether any subgroup or sensitivity analyses were conducted. It also does not report an interim-analysis plan or a sample-size justification. These details should not be inferred from the Phase II designation or from the enrollment figure.

As a general statistical explanation, over-dispersion is an issue when observed variability exceeds what a statistical model assumes; it can make standard errors too small if ignored. That concept may matter for certain models and outcomes, but no over-dispersion assessment or model is reported for this trial. The primary endpoint is described as a percentage, and the record does not identify a model that would allow a more specific discussion.

The registry also lists secondary outcomes, but does not report their results or analysis methods. When multiple outcomes are examined, multiplicity can increase the chance of at least one apparently notable finding. Whether multiplicity adjustment was planned or used is not reported in the registry record. Since no analysis results are listed, the record does not permit an assessment of how multiple outcomes were handled.

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("Pevonedistat Plus Docetaxel")
n      <- c(27)
events <- c(6)
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  Pevonedistat Plus Docetaxel  27  6  22.2  8.6  42.3  10.6  40.8  10.7  41.0

11. Multiplicity, Missing Data and Analysis Populations

The registry record identifies one primary outcome and lists secondary outcomes, but it does not report a statistical analysis plan. Whether the protocol specified a hierarchy of outcomes, multiplicity adjustment, or a particular approach to secondary analyses is not reported in the registry record. The number of analyses listed is zero. Results for the secondary outcomes are not reported in the registry record.

As a general statistical explanation, testing or estimating many outcomes can increase the chance that at least one result appears noteworthy by chance. A prespecified testing hierarchy or adjustment can help address that issue, but no such plan should be assumed. Without the analysis plan and results, it is not possible to assess how multiplicity was handled or whether reported analyses were prespecified.

The primary outcome description identifies 27 patients as evaluable, while enrollment is listed as 40. The record does not explain the participant flow between these groups or state how patients without an evaluable primary outcome were treated in the analysis. Missing-data methods, reasons for missing outcomes, and sensitivity analyses are not reported in the registry record. The figures alone do not establish that missing outcomes were excluded for any particular reason.

The analysis population is therefore only partly described: the record names the group considered evaluable for the primary outcome, but does not report whether another population was analyzed or how inclusion was determined. As a general statistical matter, excluding participants without outcome assessments can affect interpretation if their outcomes differ from those who remain evaluable. Whether that concern applies in a particular way cannot be determined from this record.

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 0% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: febrile neutropenia (6.7%), lung infections (6.7%), pleural effusion (6.7%), buttock pain (3.3%), dysphagia (3.3%).

The registry lists one treatment group, Pevonedistat Plus Docetaxel. Serious adverse events are listed for 30 participants at risk, with 12 affected. Other adverse events are listed for 30 participants at risk, with 30 affected. The record also lists 24 deaths. It does not report whether the deaths were considered related to treatment, nor does it provide enough detail to determine the timing or circumstances of each event.

The most frequently listed serious adverse-event terms include febrile neutropenia, lung infections, and pleural effusion, each reported as 6.7%. Buttock pain, dysphagia, and enterocolitis infection are each reported as 3.3%. These entries describe the registry's listed terms and percentages; they do not establish causation or provide a comparison with another treatment group.

As a general statistical explanation, adverse-event counts are descriptive unless a suitable comparator and analysis are available. A participant may experience more than one event, so event terms should not automatically be read as mutually exclusive groups. The registry record does not report further details about event coding, severity grading, exposure time, or attribution. The safety figures should therefore be read as reported counts and terms for the listed group, not as a comparative estimate of risk.

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

The registry record describes a Phase II, single-arm study of pevonedistat plus docetaxel in previously treated advanced non-small cell lung cancer. It defines a primary response outcome and identifies 27 patients as evaluable for that outcome. However, the response count, response percentage, and 85% confidence interval are not reported in the registry record. The central efficacy result therefore cannot be interpreted from the posted record.

The record also lists enrollment of 40, several secondary outcomes, and adverse-event counts for the treatment group. Results for the secondary outcomes are not reported in the registry record. The serious and other adverse-event counts, listed serious-event terms, and deaths describe safety information recorded for the group, but the record does not establish treatment attribution or provide a comparator. These figures should not be read as estimates of comparative safety.

As a general statistical explanation, a single-group study can describe outcomes observed among its participants, but it cannot by itself show how those outcomes compare with a different treatment or with no treatment. The absence of a comparator also limits causal interpretation. The registry record does not report a randomized comparison or another design feature that would support a treatment contrast.

Important information for interpretation is missing, including the primary outcome result, the reason for termination, details explaining the evaluable population, and the analysis plan. The registry does not report how missing assessments were handled or whether interim analyses were planned. These gaps prevent evaluation of the endpoint's precision, the handling of incomplete data, or the alignment between planned and reported analyses.

The record can therefore support a description of the study question, regimen, response criteria, population descriptions, and listed safety events. It cannot establish the observed response rate, the results of the secondary outcomes, or a comparative benefit-risk profile. This distinction is not a judgment about the regimen; it reflects what the registry record reports and what it leaves unreported.

14. Why This Trial Matters Statistically

This trial is statistically informative as an example of how design and reporting shape what can be concluded from a clinical study. The registry identifies a defined response endpoint in a specific population and records a single-group design. Those features clarify the question the study set out to address: the proportion of evaluable participants meeting the response criteria during the stated timeframe.

The record also illustrates why an endpoint definition and an endpoint result are different kinds of information. The response criteria are described in detail, but the response count, percentage, and confidence interval are not reported in the registry record. A clearly defined outcome is necessary for interpretation, but it does not substitute for reporting the observed estimate and its uncertainty.

The single-arm design is another important statistical feature. As a general statistical explanation, a one-group study can characterize outcomes in the group studied, but it does not provide a randomized between-group comparison. That limits conclusions about relative effects and causal attribution. The design should therefore guide the scope of any interpretation, rather than allowing descriptive outcomes to be treated as comparative evidence.

Finally, the difference between the listed enrollment of 40 and the 27 patients described as evaluable highlights the importance of transparent participant flow and missing-data reporting. The registry does not explain this difference. Without that information, readers cannot evaluate how the primary analysis population was formed or whether incomplete outcomes could affect interpretation.

The record's statistical value lies in the design and measurement information it documents, alongside the limitations created by unreported outcomes and analysis details. That distinction helps readers separate what the registry establishes from what it cannot resolve.

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.

The most consequential limitation in the registry record is that it does not report the primary response result. Although the outcome is defined and an 85% confidence interval is specified, the response count, percentage, and interval limits are absent. As a result, the primary efficacy estimate and its precision cannot be evaluated.

The record describes 40 enrolled participants and 27 participants considered evaluable for the primary outcome, but does not explain the difference or provide detailed participant flow. Reasons for non-evaluability, missing outcome assessments, and the method used to define the analysis population are not reported in the registry record. These omissions limit assessment of possible selection effects.

The trial has a single-group design and no listed comparator. Consequently, the record does not provide a randomized comparison of the regimen with another treatment or control condition. The registry also does not report results for the listed secondary outcomes, including progression-free survival, overall survival, stable disease, and toxicities by system organ class.

The study status is terminated, but the reason is not reported in the registry record. The statistical analysis plan, sample-size justification, interim-analysis plan, and methods for handling missing data or multiplicity are also not reported. These are specific gaps in the information available for this trial; none should be filled by assumptions based on its phase, enrollment, or endpoint description.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Trial of Pevonedistat Plus Docetaxel in Patients With Previously Treated Advanced Non-Small Cell Lung Cancer — NCT03228186.
• Registry record last updated 2023-10-23; status last verified 2023-10.
• Results first posted 2023-10-23.
• 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

NCT03228186 is a Phase II, single-group trial of pevonedistat plus docetaxel in previously treated advanced non-small cell lung cancer. The registry lists enrollment of 40 and describes 27 patients as evaluable for the primary response outcome. The regimen is specified as pevonedistat 25mg/m2 on days 1, 3, and 5, plus docetaxel 75mg/m2 on day 1, in a 21 day cycle.

The primary outcome is the percentage of patients achieving partial or complete response, with a timeframe of up to 2 years and an 85% confidence interval. The response result and interval limits are not reported in the registry record. The trial status is terminated; the reason is not reported. The record lists serious and other adverse-event counts and 24 deaths, but does not report attribution. Results for the listed secondary outcomes and details of the statistical analysis plan are not reported in the registry record.