Neoadjuvant Anti PD-1 Immunotherapy in Resectable Non-small Cell Lung Cancer: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Neoadjuvant Anti PD-1 Immunotherapy in Resectable Non-small Cell Lung Cancer (NCT03197467), a na phase 2 study. The primary outcome is Number of Patients Treated in Compliance With Protocol.

2. Clinical Question

This question concerns whether the study’s treatment-and-surgery sequence was completed as specified. It is not a direct comparison of pembrolizumab with another treatment, and the primary outcome is not described as a measure of tumor shrinkage or survival. The registry lists disease-free survival and overall survival at several specified time points as secondary outcomes, but their results are not reported in the registry record.

Because there is no concurrent comparison group, the study’s design does not directly estimate how outcomes would differ under another treatment strategy. The registry record also does not report a primary-outcome count or a statistical comparison for the primary outcome. The clinical question can therefore be stated from the registered endpoint, but its answer cannot be determined from the outcome information in the registry record.

3. Trial Design

NEOMUN is listed as a phase II, prospective, monocenter, open-label, single-arm study of pembrolizumab in a neoadjuvant setting. The registry describes the target population as patients with Stage II/IIIA non-small cell lung cancer suitable for curative intent surgery. The listed enrollment is 30, and the study status is completed.

The intervention is pembrolizumab at a fixed dose of 200 mg q3w i.v. For 2 cycles. The primary outcome timeframe is from screening until surgery, described as ca. 6-8 weeks. The primary outcome definition requires both neoadjuvant pembrolizumab treatment and successful curative intent tumor resection.

Allocation is listed as NA, masking as none, and the statistical model as single group. Thus, the record describes neither random allocation nor a masked comparison. There is no like-for-like control arm in this design. Results, if available, would describe the study group rather than a randomized treatment contrast.

The registry lists a start date of 2018-06-18 and a primary completion date of 2021-10-30. It lists five secondary survival outcomes: disease-free survival at 6 Months and 12 Months, and overall survival at 12 Months, 18 Months, and 24 Months. The record reports 10 outcome measures overall, but does not report analysis results for those outcomes. Details of the enrollment process, protocol deviations, and analysis populations 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.

Overall Study

Reasons for not completing this period:

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.

6. Primary Endpoint

The registry lists the primary outcome as Number of Patients Treated in Compliance With Protocol, measured over From screening until surgery, ca. 6-8 weeks.

The primary endpoint is titled Number of Patients Treated in Compliance With Protocol and is measured in participants. Its definition combines two requirements: neoadjuvant pembrolizumab treatment and successful curative intent tumor resection. The timeframe runs from screening until surgery, described as ca. 6-8 weeks.

This endpoint measures completion of a planned treatment-and-surgery pathway. It can describe whether participants reached the specified surgical step after receiving the neoadjuvant treatment. As a count, it is a binary-outcome summary in which each participant either meets the endpoint definition or does not. The registry record does not state a more detailed rule for classifying partial treatment, unsuccessful resection, or other departures from the pathway.

Such an endpoint can be useful for describing protocol delivery and the feasibility of completing the intended sequence in the studied group. It does not, by itself, quantify tumor response, establish a survival effect, or show what would have happened under a different treatment. The record does not report the number meeting the definition, the number assessed, or an estimate of uncertainty for the primary endpoint. Accordingly, the endpoint’s definition is available, but its observed result is not reported in the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The statistical methods described by a registry record determine how outcomes are converted into estimates and how uncertainty is assessed. For NEOMUN, the record identifies a single-group model and a binary primary outcome expressed as a count of participants. It reports no analyses. The details of the primary-outcome analysis, including any interval estimation or hypothesis test, are not reported in the registry record.

What does a participant count represent?

The primary endpoint is defined by whether a participant received neoadjuvant pembrolizumab and then underwent successful curative intent tumor resection. A count would tally the participants meeting that definition. A count alone does not indicate the proportion of all eligible or treated participants unless its denominator is also specified. Although the record lists enrollment of 30, it does not report the primary endpoint count or the analysis denominator. It is therefore not possible to infer a rate from the endpoint definition and enrollment entry.

For a binary outcome, an analysis may report a count, a proportion, or an estimate with an uncertainty interval. The registry record does not report which additional summary measures were used for the primary outcome. In general, a confidence interval describes the range of values compatible with the data under the method’s assumptions; it is not a guarantee that the true value lies within that particular interval. No primary-outcome confidence interval is reported in the registry record.

What can a single-group design estimate?

A single-group design can describe outcomes among participants who entered the study. Without a concurrent randomized comparator, it does not directly estimate a treatment contrast against another strategy. A before-and-after or external comparison would require further data and assumptions, neither of which is reported in the registry record. The design classification itself does not establish how participants would have fared under an alternative treatment.

Masking is listed as none, and allocation is listed as NA. These entries are consistent with the record’s description of an open-label, single-arm study. The registry does not report additional procedures for reducing outcome-assessment bias or handling departures from the planned treatment sequence. Such procedures should not be assumed.

How should survival outcomes be read?

The registry names disease-free survival at 6 Months and 12 Months, and overall survival at 12 Months, 18 Months, and 24 Months. These are time-to-event outcomes in which interpretation generally depends on the event definition, follow-up, censoring, and the analysis method. In general, censoring occurs when a participant’s event time is not observed during the available follow-up; appropriate methods account for the resulting incomplete information. The specific event definitions, censoring rules, estimators, and survival results are not reported in the registry record.

For time-to-event outcomes, an estimate at a specified time point does not by itself reveal the number of events, the amount of follow-up, or the precision of the estimate. Those details are not reported for the listed survival outcomes. Nor does the record report a hazard ratio or another comparative estimate. The listed outcome names should therefore be read as registered endpoints, not as evidence that results at those times are available.

What do the planning assumptions mean?

The registry description of sample-size assumptions says that planning illustrations use a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation, with the effect to detect stated as a fraction of the observed effect. It specifies that time-to-event illustrations count total events using Schoenfeld, while other illustrations express participants per arm. These are planning assumptions, not a description of the NEOMUN design: the trial is listed as single-group, not a two-arm randomized comparison.

In general, a sample-size calculation is conditional on its assumptions about effect, variability, allocation, and analysis. It is not observed power and does not establish that a study produced a particular result. The registry record does not report the trial’s own sample-size justification or enough primary-outcome results to interpret the planning illustrations as a trial-specific analysis.

Over-dispersion is relevant in general when observed variation exceeds what a statistical model assumes; ignoring it can make uncertainty estimates too small. The registry record does not identify an over-dispersion analysis for this trial. No model details beyond the single-group classification are reported.

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("Pembrolizumab")
n      <- c(29)
events <- c(29)
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  Pembrolizumab  29  29  100.0  88.1  100.0  88.3  100.0  88.4  99.9

11. Multiplicity, Missing Data and Analysis Populations

The registry lists 10 outcome measures and identifies five secondary survival outcomes: disease-free survival at 6 Months and 12 Months, and overall survival at 12 Months, 18 Months, and 24 Months. The remaining outcome measures are not detailed in the registry record for this description. The number of listed outcomes alone does not establish whether statistical testing was planned for each one.

When several outcomes or time points are analyzed, the chance of at least one apparently noteworthy result can increase if each is tested separately without a multiplicity strategy. General approaches include designating a primary outcome, specifying a hierarchy, or adjusting inference across a family of tests. The registry record does not report a multiplicity plan, a testing hierarchy, or whether any adjustment was used. It would be inappropriate to assume that one was or was not applied.

The registry reports 0 analyses. Outcome estimates, statistical tests, and uncertainty intervals are not reported in the registry record for the primary endpoint or the listed survival outcomes. Missing-data rules, censoring rules, and the handling of participants who did not complete the treatment-and-surgery sequence are also not reported. The analysis populations, such as whether all enrolled participants or only those completing treatment were included, are not reported in the registry record.

These omissions affect what can be learned from the listing. Without results and analysis definitions, readers cannot assess how much information was available for each outcome, whether follow-up was complete, or how missing observations may have affected estimates. They also cannot determine whether the reported enrollment corresponds to every outcome’s analysis population.

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: pneumonia (6.9%), hyperthyroidism (3.4%), colitis (3.4%), gastritis (3.4%), acute hepatic failure (3.4%).

The registry lists 29 participants at risk for the pembrolizumab group’s serious adverse event summary and reports 8 affected. It lists 21 participants with other adverse events among 29 at risk, and 5 deaths. These counts are safety summaries, not evidence by themselves that pembrolizumab caused an event or death.

The serious-event terms listed include pneumonia at 6.9%, and hyperthyroidism, colitis, gastritis, acute hepatic failure, and herpes zoster at 3.4% each. The registry presents these as serious adverse event terms. It does not report the event-level details, timing, seriousness criteria, attribution to treatment, or whether participants could contribute more than one event. The percentages should therefore be read as posted, without assuming a specific denominator or that each term represents a distinct participant.

Safety counts are most informative when read with definitions, follow-up duration, exposure, and attribution procedures. These details are not reported in the registry record. Nor is a comparator group available for a between-group safety comparison. The listed counts and terms describe reported safety information, but do not establish comparative risk or causation.

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

The record establishes that NEOMUN was registered as a phase II, prospective, monocenter, open-label, single-group study of neoadjuvant pembrolizumab in patients with Stage II/IIIA non-small cell lung cancer suitable for curative intent surgery. It defines the primary endpoint as the number of participants treated according to the specified sequence and reports an enrollment of 30. It also lists survival outcomes and selected safety summaries.

What the record does not establish is the numerical result for the primary endpoint. That count is not reported in the registry record, nor are outcome estimates for the listed survival time points. The registry’s status of completed indicates the recorded study status; it does not substitute for outcome data or an analysis.

Because the study is single-group, its design does not provide a randomized comparison with another treatment. Even a complete description of outcomes in the study group would not, on its own, show what would have occurred under an alternative strategy. The registry record also does not report a formal statistical analysis, uncertainty estimates, or analysis populations. As a result, precision and the influence of missing information cannot be evaluated from the listing.

The safety entries should likewise be interpreted descriptively. They report adverse-event counts and serious-event terms, but do not establish treatment causation or comparative safety. The counts do not replace details about event timing, follow-up, attribution, or exposure.

The most defensible reading is therefore limited: the registry specifies a treatment pathway, a process-focused primary endpoint, secondary survival outcomes, and selected safety summaries, but does not report the outcome analyses needed to quantify efficacy or precision. Any stronger conclusion would go beyond the information reported in the registry record.

14. Why This Trial Matters Statistically

NEOMUN illustrates how a trial’s question and its endpoint can differ from a direct measure of treatment effect. Its primary endpoint is a count of participants completing a defined neoadjuvant-treatment and surgery sequence. That endpoint addresses whether the pathway was completed, rather than directly comparing tumor response or survival between treatment strategies.

The single-group design is central to statistical interpretation. It can provide descriptive information about outcomes among study participants, but it cannot create a randomized counterfactual comparison. A reader must distinguish feasibility or treatment-pathway completion from comparative efficacy. The registry does not report the primary count, so even the descriptive answer to the registered primary question is unavailable in the record.

The listing also emphasizes the importance of reporting analysis details alongside outcome names. The survival endpoints are specified by time point, but the record does not report their estimates, event definitions, censoring rules, or uncertainty. Without those elements, readers cannot judge the amount of information supporting an estimate or its precision.

Finally, the planning assumptions describe calculations based on a two-arm allocation framework, while the registered study design is single-group. Planning illustrations can help explain assumptions, but they should not be mistaken for observed trial evidence or for a randomized design that was not used. The record’s lack of reported analyses makes that distinction particularly important.

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 primary limitation for statistical interpretation is that the registry record does not report the primary endpoint result. It provides the endpoint definition and lists enrollment of 30, but not the number meeting the definition, the denominator analyzed, or an estimate of uncertainty. The registry lists 0 analyses.

The single-group design provides no concurrent comparator, so it cannot directly estimate a randomized difference between pembrolizumab and another strategy. The open-label designation and absence of masking are recorded, but further details about outcome assessment and mitigation of bias are not reported in the registry record.

Although disease-free and overall survival outcomes are listed, their event definitions, follow-up completeness, censoring procedures, estimates, and uncertainty intervals are not reported. The record also does not report missing-data handling, analysis populations, protocol-deviation rules, or multiplicity procedures. These gaps prevent assessment of how incomplete follow-up or multiple outcomes may affect interpretation.

Safety information is limited to counts and selected serious-event terms. Event timing, attribution, exposure, and the detailed counting rules are not reported. Consequently, the safety entries cannot support a causal or comparative interpretation. The registry record also does not report the trial’s own sample-size justification. The planning assumptions described in the record should not be treated as proof of adequate power or as observed trial results.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Neoadjuvant Anti PD-1 Immunotherapy in Resectable Non-small Cell Lung Cancer — NCT03197467.
• Registry record last updated 2025-04-04; status last verified 2025-04.
• Results first posted 2025-04-04.
• 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

NEOMUN is registered as a completed phase II, prospective, monocenter, open-label, single-group study of neoadjuvant pembrolizumab for Stage II/IIIA non-small cell lung cancer suitable for curative intent surgery. The record lists enrollment of 30 and pembrolizumab at 200 mg q3w i.v. For 2 cycles.

The primary endpoint is the number of participants treated in compliance with protocol, defined as neoadjuvant pembrolizumab followed by successful curative intent tumor resection. Its timeframe is from screening until surgery, ca. 6-8 weeks. Five secondary survival outcomes are listed. The registry reports 10 outcome measures and 0 analyses.

The record lists 8 participants with serious adverse events among 29 at risk, 21 with other adverse events among 29 at risk, and 5 deaths. It does not report the primary endpoint result, survival estimates, or inferential analyses. The single-group design has no concurrent comparator.