Trial of Consolidation Pembrolizumab After Concurrent Chemotherapy and Proton Reirradiation for Thoracic Recurrences of Non-Small Cell Lung Cancer: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Trial of Consolidation Pembrolizumab After Concurrent Chemotherapy and Proton Reirradiation for Thoracic Recurrences of Non-Small Cell Lung Cancer (NCT03087760), a na phase 2 study. The primary outcome is Number of Subjects With Progression Free Survival.

2. Clinical Question

3. Trial Design

This is a phase II, single-group, open-label trial sponsored by Abramson Cancer Center at Penn Medicine. The registry record lists an enrollment of 32 participants and the condition as non-small cell lung cancer. The intervention is pembrolizumab. The title describes consolidation pembrolizumab after concurrent chemotherapy and proton reirradiation for thoracic recurrences; the brief summary describes the intended study population as people whose cancer returned after radiation therapy.

The design has no randomized allocation and no separate control arm. That matters when interpreting outcomes: observed results in the treated group cannot, on their own, distinguish treatment-associated changes from the course participants might have experienced under a different approach. The open-label designation means the trial is not described as masked. Further details about outcome assessment safeguards or blinding of reviewers are not reported in the registry record.

The trial status is completed. Its listed start date is 2017-11-29, and its primary completion date is 2023-09-12. These dates describe the registry record; they do not establish when each participant started or finished treatment. The record lists two outcome measures, including the primary progression-free survival count and a secondary measure of participants who experienced a grade 3+ adverse event. It does not report a statistical analysis or numerical primary outcome result. Details of the treatment schedule, eligibility criteria, follow-up schedule beyond the endpoint timeframe, and protocol deviations 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: Between November 2017 and April 2021, 32 patients were consented and reviewed for eligibility, of which 10 were excluded. Most common reasons for exclusion were internal clinical target volume (iCTV) ≥250 cc on the simulation scan (n = 3), histology other than non-small cell lung cancer (NSCLC) (n = 3), and extrathoracic metastases (n = 2). Twenty-two patients initiated proton beam therapy (PBT) reirradiation (reRT) on-trial and were included in the intention-to-treat analysis.

Overall Study

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 Subjects With Progression Free Survival, measured over 2 years.

The primary endpoint is the number of subjects with progression-free survival at 2 years. The registry defines progression-free survival as the time from initiation of definitive therapy to the first documented disease progression under RECIST 1.1, based on radiologists’ review, or death from any cause, whichever occurs first. It also refers to the last follow-up documenting no progression. Participants without documented progression or death are described as censored at the most recent clinical evaluation that documented they were progression-free.

As general statistical context, progression-free survival combines disease progression and death into an outcome that reflects time without either event. Censoring allows participants with no recorded event by their last suitable evaluation to contribute information up to that point, rather than treating their later outcome as known. It does not establish what happened after their last evaluation. The registry presents the primary outcome as a participant count, not as a reported survival curve or effect estimate. Neither the count nor an estimate of progression-free survival at the stated timeframe is reported in the registry record, so the endpoint’s observed magnitude and precision cannot be assessed from the posted results.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The statistical information available for this trial is limited. The registry identifies the primary endpoint as a participant count for progression-free survival and records two outcome measures, but it lists no analyses. A statistical analysis plan, model specification, estimation procedure, or inferential result is not reported in the registry record. It is therefore important to separate the endpoint definition from any statistical method that might have been used to analyze it: the definition is recorded, but an analysis method cannot be inferred from that definition alone.

What does a participant count represent?

The primary endpoint is expressed as the number of subjects with progression-free survival at the stated 2 years. A count reports how many people meet a specified outcome definition within a population; by itself, it does not describe the timing of events for each participant or quantify uncertainty. A proportion or a survival estimate would require a defined analysis and denominator, and no such estimate is reported in the registry record. No extra calculation should be inferred from the enrollment figure because the endpoint population and the outcome count are not posted.

General statistical context: binary outcomes classify each participant according to whether an event or condition is present under a stated definition. Analyses of binary outcomes can describe counts or proportions and may compare groups when a suitable comparison is part of the design. In this trial, the primary endpoint is recorded as a count and the design is single-group. The registry record does not state whether the primary analysis treated the outcome as a simple count, used time-to-event methods, or applied another procedure.

How does censoring relate to progression-free survival?

The endpoint definition uses time from initiation of definitive therapy to progression or death, and describes censoring participants at the most recent clinical evaluation documenting that they were progression-free. Censoring is a way to retain the information available up to a participant’s last relevant assessment when the event of interest has not been observed by then. It does not mean the participant remained progression-free after that assessment, and it does not reveal their later status. The record does not report the number censored, follow-up distribution, or detailed handling of censoring in an analysis.

General statistical context: time-to-event methods can use both event timing and the information contributed before censoring. Their interpretation depends on the endpoint definition, follow-up, and assumptions about how censoring relates to the event. Those methods cannot be presumed merely because an endpoint is called progression-free survival. The registry does not identify a survival estimator, model, or assumptions used for this trial, so none should be attributed to the reported outcome.

What can uncertainty measures add?

General statistical context: a confidence interval communicates sampling uncertainty around an estimate under the method used to construct it. A narrow interval indicates greater precision under that method, while a broad interval indicates less precision. Neither interval width nor a p-value addresses all sources of bias, and neither turns a single-group study into a randomized comparison. The registry record does not report a primary estimate, confidence interval, or p-value, so precision and statistical compatibility with particular values cannot be evaluated.

The record includes a secondary outcome measuring the number of participants who experienced a grade 3+ adverse event. It also lists serious and other adverse-event counts. Counts are useful descriptive summaries, but interpretation depends on definitions, observation time, and the population included. Those details are not reported in the registry record. The listed serious-event terms and percentages are descriptive entries; they are not, by themselves, an analysis comparing risk across treatments.

How should planning illustrations be understood?

General statistical context: sample-size calculations describe how many participants might be needed under specified design assumptions to target a chosen level of power for a particular effect. Such calculations are planning illustrations, not evidence that a study had a particular probability of detecting an effect after the fact. The record describes an illustration based on the observed effect, a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. It also states that the effect to detect is a specified fraction of the observed effect. These are described as planning assumptions, not as the trial’s own design; this trial itself is single-group. The numerical planning results and the observed effect are not reported in the registry record. They therefore cannot be used to infer observed power or a treatment effect for this trial.

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("Single Arm")
n      <- c(22)
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  Single Arm  22  6  27.3  10.7  50.2  13.2  48.2  13.2  48.4

11. Multiplicity, Missing Data and Analysis Populations

The registry lists two outcome measures: progression-free survival as the primary outcome and the number of participants who experienced a grade 3+ adverse event as a secondary outcome. It does not report how multiple outcomes or multiple statistical tests were handled. A multiplicity adjustment, hierarchy of hypotheses, prespecified testing sequence, or distinction between confirmatory and exploratory analyses is not reported in the registry record. With no analyses listed, there is no posted inferential result for which the impact of multiple testing can be assessed.

Missing-data handling is described only in the primary endpoint definition’s reference to censoring. Participants without documented progression or death are described as censored at the most recent clinical evaluation documenting progression-free status. The registry does not report how many participants were censored, whether other missing assessments occurred, or how missing information was handled for the secondary outcome and safety summaries. It also does not describe sensitivity analyses examining alternative assumptions about missing outcomes.

The analysis populations are not defined in the registry record. Enrollment is 32, while the safety summaries report 22 at risk for serious events and 22 at risk for other adverse events. The reason these reported safety populations differ from enrollment is not stated. The record does not identify an intention-to-treat population, a per-protocol population, or an efficacy population, so these labels should not be assigned to the reported data. The statistical analysis plan, interim analyses, and sample-size justification for the trial are not reported in the registry 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: lymphopenia (22.7%), esophagitis (13.6%), neutropenia (9.1%), hemoptysis (4.5%), pneumonitis (4.5%).

The registry reports one single-arm safety group with 22 participants at risk for serious adverse events and 10 affected. For other adverse events, it reports 22 at risk and 16 affected. It also lists 14 deaths. These are descriptive counts; the record does not explain the difference between enrollment of 32 and the 22 participants at risk in the safety summaries, nor does it state the causes or timing of the deaths.

The listed serious-event terms include lymphopenia at 22.7%, esophagitis at 13.6%, neutropenia at 9.1%, hemoptysis at 4.5%, pneumonitis at 4.5%, and tracheal rupture at 4.5%. These registry entries do not establish that events were caused by pembrolizumab, and they do not provide a comparison with another treatment group. The record does not report the duration of safety observation, detailed event definitions, or whether one participant could contribute to more than one event term. The secondary outcome specifically concerns participants who experienced a grade 3+ adverse event, but the result for that outcome is not reported in the registry record.

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

The record establishes that a phase II, open-label, single-group trial was conducted to assess pembrolizumab after concurrent chemotherapy and proton reirradiation in the setting of thoracic recurrences of non-small cell lung cancer. It defines progression-free survival and identifies a 2-year primary outcome timeframe. It also reports safety counts and selected serious adverse-event terms. These details describe the study question, design, endpoint, and some posted safety information.

They do not establish the size or precision of the primary outcome. The registry does not report the primary outcome count, a progression-free survival estimate, a confidence interval, or a p-value. It also does not report an analysis of the secondary grade 3+ adverse-event outcome. The absence of a posted result should not be interpreted as a favorable or unfavorable result; it means the relevant result is not reported in the registry record.

Even if a primary outcome estimate were available, a single-group design would not directly show how outcomes compare with those under another treatment or with no pembrolizumab. Differences between the participants’ observed outcomes and an external expectation could reflect factors beyond the intervention, and the registry does not supply a control group for separating those influences. The open-label design is recorded, while additional details about outcome-assessment procedures are not reported.

General statistical context: statistical significance, precision, and clinical importance are distinct ideas. A p-value addresses compatibility of data with a specified statistical model; a confidence interval conveys uncertainty around an estimate; neither alone determines clinical importance or establishes causality. Since the primary analysis and its uncertainty are not reported, these dimensions cannot be evaluated from the registry record. The safety counts and event percentages should likewise be read as descriptive entries rather than comparative evidence or proof that an intervention caused an event.

14. Why This Trial Matters Statistically

This trial is statistically notable for the gap between a clearly defined time-to-event concept and the form of the posted primary outcome. The registry defines progression-free survival using time from initiation of definitive therapy to progression or death, with censoring described, but lists the primary result as a number of subjects with progression-free survival at 2 years. No corresponding count or survival estimate is reported. This makes the endpoint definition available while leaving its observed magnitude and precision unavailable.

The single-group design is central to interpretation. Without a concurrent comparison group, the study can describe outcomes among participants in the trial but cannot estimate a randomized between-group treatment contrast. This distinction remains important even when an endpoint is clinically meaningful and follow-up is described. The registry’s open-label designation and lack of posted analysis details add limits to evaluating how outcome assessment and uncertainty were handled.

The safety information illustrates a separate reporting issue: enrollment is 32, while the listed safety summaries each have 22 participants at risk. The registry does not explain that difference. The counts and serious-event percentages can be reported as recorded, but without information on the safety population, observation time, and event ascertainment, the precision and scope of those summaries are difficult to judge.

General statistical context: transparent reporting of analysis populations, endpoint results, uncertainty, and missing-data handling allows readers to distinguish descriptive observations from estimates that support inference. Those elements are not all reported in the registry record. The trial therefore offers a defined research question and selected outcome and safety descriptions, but the posted information does not support a quantitative assessment of the primary endpoint or a comparison of treatment effects.

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 interpreting efficacy is that the registry record does not report the primary outcome result or any analysis. The number of participants with progression-free survival at 2 years, a survival estimate, and measures of uncertainty are absent. The record also does not report the result for the secondary grade 3+ adverse-event outcome. Without these results, the magnitude and precision of the outcomes cannot be assessed.

The single-arm, open-label design has no concurrent comparator. It therefore cannot isolate a treatment contrast from other influences on outcomes. The registry does not report a statistical analysis plan, sample-size justification, interim analyses, or analysis populations. It also does not describe multiplicity control or sensitivity analyses for missing data. Although censoring is addressed in the endpoint definition, the amount of censoring and its handling in any analysis are not reported.

Safety interpretation is limited by the unexplained difference between enrollment of 32 and the 22 participants at risk listed for each safety summary. The record does not report the safety observation period, detailed event ascertainment methods, or whether event categories could overlap. It lists 14 deaths without reporting their timing or causes in the posted trial details. The listed event percentages are not comparative estimates, and the record does not establish attribution to the intervention.

Further details about participant characteristics, eligibility, treatment schedules, and follow-up beyond the primary endpoint timeframe are not reported in the registry record. These gaps limit assessment of generalizability, outcome completeness, and reproducibility of the statistical analysis.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Trial of Consolidation Pembrolizumab After Concurrent Chemotherapy and Proton Reirradiation for Thoracic Recurrences of Non-Small Cell Lung Cancer — NCT03087760.
• Registry record last updated 2024-01-18; status last verified 2024-01.
• Results first posted 2024-01-11.
• 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

The registry record describes a completed phase II, open-label, single-group trial sponsored by Abramson Cancer Center at Penn Medicine. Enrollment was 32. The listed intervention was pembrolizumab, in the context of concurrent chemotherapy and proton reirradiation for thoracic recurrences of non-small cell lung cancer. The listed start date is 2017-11-29 and the primary completion date is 2023-09-12.

The primary endpoint is the number of subjects with progression-free survival at 2 years, defined using progression under RECIST 1.1 or death from any cause, with censoring described. The registry record lists two outcome measures and no analyses. It reports safety counts for 22 participants at risk in each of the serious and other adverse-event summaries, along with selected serious-event terms and 14 deaths. The primary outcome result, statistical analysis, and several details needed to interpret efficacy and safety are not reported in the registry record.