A Study of Pembrolizumab in Patients With Advanced Gynaecological Clear Cell Cancer: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for A Study of Pembrolizumab in Patients With Advanced Gynaecological Clear Cell Cancer (NCT03425565), a na phase 2 study. The primary outcome is Progression Free Survival at 12 Weeks.

2. Clinical Question

3. Trial Design

The registry describes PEACOCC as a multi-centre, single-arm, single-stage phase II trial of pembrolizumab in patients with advanced clear cell gynaecological cancer. Its stated overall aim was to determine whether pembrolizumab was effective in this population. The study is recorded as completed, with an enrollment of 48. The recorded start date is 2019-02-18 and the primary completion date is 2024-07-24.

A single-arm design follows participants receiving the study intervention without a concurrent control arm. The primary endpoint can therefore describe the observed progression-free proportion in the study population, but it cannot by itself estimate a treatment difference against a control group. Differences between this study and other groups or studies would not be randomized comparisons.

Allocation is listed as not applicable, masking as none, and the model as single group. These features are consistent with the registry's single-arm description. Random assignment and masking are not described as part of the study design. The registry record does not report a statistical analysis plan, sample-size justification, or details of how the single-stage design was specified.

Progression-free survival, time to second disease progression during a re-treatment period, overall survival, response measures, duration of response, and quality-of-life measures are among the listed secondary outcomes. The record lists 13 outcome measures and no analyses. The detailed result for the primary endpoint, including the number meeting the endpoint and its confidence interval, is not reported in the registry record. Consequently, the design and intended endpoint can be described, but the primary observed result cannot be assessed from the registry information used.

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: Participants had a histological diagnosis of advanced gynaecological clear cell cancer with presence of ≥50% clear cell component. For trial entry, participants needed to have radiological confirmation of disease progression, ECOG performance status 0/1, life expectancy of at least 4 months from consent to trial, received ≥ 1 line of prior chemotherapy, and have adequate organ function. Participants needed to meet all protocol eligibility inclusion and exclusion criteria.

Overall Study

Analysis population for the primary outcome, as defined in the registry: All trial participants who were registered and received at least one cycle of trial treatment were included in analysis.

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: All trial participants who were registered and received at least one cycle of trial treatment were included in analysis.

6. Primary Endpoint

The registry lists the primary outcome as Progression Free Survival at 12 Weeks, measured over 12 weeks.

The primary endpoint is the proportion of participants who were progression-free at 12 weeks. The registry defines this as the number alive with complete response, partial response, or stable disease maintained at that time, divided by the number of participants in the analysis population. Tumour assessment was based on RECIST v1.1 and was made by the site radiologist and/or investigator. Only participants with tumour assessment at or beyond 12 weeks were considered progression-free.

A proportion gives an absolute description of how often the defined status was observed in the analyzed group. It combines the endpoint definition with the assessment time: being alive and having one of the specified disease statuses at the specified assessment is what counts. This makes the measure interpretable as a group-level summary, but it does not describe every participant's course or provide a comparison with an alternative treatment.

The registry specifies a 95% confidence interval as the measure of uncertainty for the primary endpoint. In general, a confidence interval describes the statistical precision of an estimate under the method used; a wider interval indicates greater uncertainty about the underlying proportion. Neither the observed proportion nor its confidence interval is reported in the registry record, so the magnitude and precision of the primary endpoint cannot be evaluated from the recorded information.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The statistical information in the registry is enough to identify the primary outcome as a proportion and to describe its stated uncertainty measure, but not enough to reconstruct the primary analysis. The registry record does not report an analysis method, the observed numerator and denominator, or a confidence-interval calculation. The explanation below describes the general statistical ideas relevant to this endpoint rather than asserting which procedures were used.

What does a proportion estimate?

For a binary endpoint, each participant is classified according to whether the defined event or status was observed. The estimated proportion is the number meeting the definition relative to the number in the analysis population. Here, the qualifying status is being alive with complete response, partial response, or stable disease maintained at 12 weeks, subject to the assessment rule in the registry. The estimate would summarize the analyzed group, not predict an individual participant's outcome.

The analysis population matters because both the numerator and denominator depend on who is included and how status is classified. The registry states that all eligible participants registered and receiving at least one cycle of trial treatment were included. It also says ineligible participants would be excluded and replaced. The number meeting the endpoint and the number actually analyzed are not reported in the registry record, so the proportion cannot be checked or independently reproduced.

What does a confidence interval add?

In general, a confidence interval communicates uncertainty around an estimated quantity. For a proportion, its width depends in part on the amount of information available and the estimation procedure. A narrower interval indicates greater statistical precision; a wider interval indicates less precision. The registry specifies a 95% confidence interval for the primary endpoint, but does not report its limits or the method used to calculate them. No conclusion about the precision of the primary estimate is therefore possible.

A confidence interval is not a guarantee that a particular interval contains the true value, nor does it address every source of uncertainty. It reflects sampling uncertainty under the assumptions of its method. It does not resolve questions about selection into the analysis population, endpoint assessment, missing observations, or whether results from a single-arm study generalize to other populations.

Why does the single-group design matter?

With one group receiving pembrolizumab and no concurrent control arm, the primary proportion is descriptive of that group. A randomized comparison would use differences between assigned groups to estimate a treatment contrast. That contrast is not available in a single-group study. Historical or external comparisons, if attempted, would require additional information and assumptions; such a comparison is not described in the registry record.

The study is characterized as single-stage, but the registry record does not report the operating details of that design, such as a decision threshold or a statistical stopping rule. The terms “phase II” and “single-stage” do not, by themselves, establish the analysis method or the strength of evidence for a treatment effect.

How should planning illustrations be understood?

Any sample-size calculations described alongside the results are planning illustrations based on an observed effect, not the trial's own design justification. The stated assumptions are 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. Such calculations explore what a future comparison might require under those assumptions. They do not describe the actual single-arm design, do not show the study's observed power, and do not provide an estimate of clinical benefit.

The registry record does not report the sample-size justification for this trial. The planning assumptions should therefore be kept separate from the trial's enrollment and analysis. Planning for a hypothetical two-arm comparison is not evidence that this study had two arms, and a planning illustration cannot substitute for the missing primary endpoint estimate and confidence interval.

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(48)
events <- c(20)
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  48  20  41.7  27.6  56.8  28.8  55.7  28.8  55.8

11. Multiplicity, Missing Data and Analysis Populations

The registry lists a range of secondary outcomes in addition to the primary progression-free proportion at 12 weeks. These include progression-free survival, time to second disease progression during a re-treatment period, overall survival, response outcomes, duration of response, and quality-of-life scores. When multiple outcomes are examined, the chance of at least one apparently notable result can increase if each is interpreted independently. A prespecified multiplicity strategy can address that issue, but a strategy for handling multiple outcomes is not reported in the registry record.

The record lists 13 outcome measures and no analyses. This does not establish how many analyses were performed outside the registry entry; it means the registry information does not provide an analysis listing from which to assess outcome-specific methods, testing order, or multiplicity adjustments. No inferential claims about secondary outcomes can be evaluated without their results and analysis details.

The primary endpoint description specifies that only participants with tumour assessment at or beyond 12 weeks were considered progression-free. It also defines the analysis population as eligible participants registered and receiving at least one cycle of trial treatment, with ineligible participants excluded and replaced. The registry does not explain how participants without an assessment at or beyond 12 weeks were classified, whether any other missing data occurred, or what sensitivity analyses were planned. The missing-data handling beyond the stated assessment rule is not reported in the registry record.

The distinction between the endpoint assessment rule and a general missing-data method is important. The rule tells readers which assessments count as evidence of being progression-free; it does not fully describe how every participant lacking such an assessment contributes to the analysis. The actual analysis denominator, exclusions, replacements, and missingness 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: fever (6.2%), abdominal pain (4.2%), acute kidney injury (4.2%), alanine aminotransferase increased (4.2%), ascites (4.2%).

The safety figures describe events recorded in the pembrolizumab group, not a comparison of safety between treatments. The registry lists 48 participants at risk for serious adverse events, 18 affected by serious adverse events, 48 at risk for other adverse events, and 48 affected by other adverse events. It also lists 40 deaths. These are registry counts; they do not establish that an event or death was caused by pembrolizumab. The registry record does not provide the attribution details needed to make that judgment.

The serious adverse event terms listed most prominently are fever at 6.2%, abdominal pain at 4.2%, acute kidney injury at 4.2%, alanine aminotransferase increased at 4.2%, ascites at 4.2%, and aspartate aminotransferase increased at 4.2%. These are the recorded percentages for the listed terms. The registry information used does not specify the calculation denominator for these percentages or explain whether participants could contribute to more than one term. The percentages should not be added together or read as mutually exclusive categories.

Serious adverse events and other adverse events are separate registry categories. The figures do not describe severity, timing, duration, management, or causal attribution in detail. They also cannot be compared with a control group in this single-arm study. The counts and listed terms should therefore be read as descriptive safety reporting, with the limits of the registry detail kept in view.

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

The registry record establishes that a completed, single-arm phase II study evaluated pembrolizumab in patients with advanced gynaecological clear cell cancer. It defines the primary outcome as the proportion of eligible participants who were alive with complete response, partial response, or stable disease maintained at 12 weeks, using assessment based on RECIST v1.1. It also states the intended analysis population and lists other outcomes, including survival, response, and quality-of-life measures.

The record does not report the numerical primary endpoint result, its confidence interval, or the number of participants contributing to the primary analysis. It therefore does not support a conclusion about the observed progression-free proportion or the precision of that estimate. Enrollment is not a substitute for an analysis denominator or an outcome count.

Even if the primary proportion were available, a single-group study would describe outcomes among participants treated in the study rather than provide a randomized estimate of the difference between pembrolizumab and a comparator. The design cannot separate the treatment's contribution from other influences on outcomes by means of a concurrent randomized comparison. No claim that the treatment works or does not work follows from the design description alone.

The secondary outcomes and safety figures add context about what the registry tracked, but they do not remove these limitations. Their results, analysis methods, and interpretation details are not fully reported in the registry record. Safety counts do not establish causation, and percentages for listed adverse event terms do not describe a comparative risk.

The appropriate reading is therefore bounded: the record documents the trial's population, intervention, design, endpoint definition, and selected safety counts, while leaving the primary numerical result and important analytical details unreported. Those omissions prevent an assessment of the magnitude and statistical precision of the primary outcome from the registry record alone.

14. Why This Trial Matters Statistically

This trial is statistically informative as an example of how a single-arm phase II study frames a clinical question through a prespecified time-specific proportion. The endpoint is concrete: it combines survival status, tumour response or stability, and an assessment time. Its definition makes clear what qualifies as progression-free for this measure, rather than leaving readers to infer the meaning of the label.

The design also illustrates the distinction between describing an outcome and estimating a comparative treatment effect. A single-group proportion can summarize what was observed in the treated study population, but it does not supply a concurrent randomized benchmark. That distinction matters when readers interpret phase II evidence or compare results across studies with different populations, assessment procedures, and analysis rules.

The registry's explicit analysis-population description is relevant because a proportion depends on who is counted and how participants without qualifying assessments are handled. The stated inclusion of eligible registered participants who received at least one cycle, the exclusion and replacement of ineligible participants, and the assessment requirement at or beyond 12 weeks are important elements of the endpoint's interpretation. At the same time, the absence of a reported numerator, denominator, and confidence interval prevents readers from judging the observed estimate or its precision.

The trial also highlights why registry completeness is part of statistical interpretation. Listing outcomes and design features is not equivalent to reporting results, analysis methods, or missing-data decisions. The record can clarify the intended question while leaving the empirical answer unavailable. That separation is essential: a well-defined endpoint is useful, but it cannot replace the result needed to quantify what was observed.

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 trial-specific limitations follow from the registry information. First, the study is single-arm, with allocation recorded as not applicable and no masking. There is no concurrent control group, so the design does not yield a randomized treatment contrast. Any interpretation of outcomes must remain descriptive unless additional comparative evidence is available; no such comparison is reported in the registry record.

Second, the primary endpoint depends on assessment at or beyond 12 weeks and on classifications of complete response, partial response, or stable disease maintained at that time. The registry identifies RECIST v1.1 and says assessment was by the site radiologist and/or investigator, but does not report additional assessment procedures or how disagreements were handled. It also does not report the number with an eligible assessment or the observed endpoint numerator.

Third, the registry defines an analysis population based on eligibility, registration, and receipt of at least one cycle, and states that ineligible participants would be excluded and replaced. The actual number analyzed, exclusions, replacements, and handling of participants without a qualifying assessment are not reported in the registry record. The enrollment figure alone cannot answer those questions.

Finally, the primary endpoint estimate and confidence interval are not reported, and the registry lists no analyses. The statistical analysis plan, multiplicity approach, sample-size justification, and missing-data methods are not reported in the registry record. These gaps limit assessment of precision, robustness, and the relationship between the recorded endpoint definition and any numerical result. The safety figures are likewise descriptive and lack detailed attribution and comparative context.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: A Study of Pembrolizumab in Patients With Advanced Gynaecological Clear Cell Cancer — NCT03425565.
• Registry record last updated 2026-09-22; status last verified 2026-09.
• Results first posted 2026-09-22.
• 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, multi-centre, single-arm, single-stage phase II study of pembrolizumab for advanced gynaecological clear cell cancer. Enrollment is recorded as 48. The start date is 2019-02-18 and the primary completion date is 2024-07-24.

The primary endpoint is the proportion alive with complete response, partial response, or stable disease maintained at 12 weeks, assessed using RECIST v1.1. The record specifies a 95% confidence interval and describes an analysis population of eligible participants who were registered and received at least one cycle of treatment.

The numerical primary result, its confidence interval, the actual analysis count, and detailed statistical methods are not reported in the registry record. Listed secondary outcomes include survival, response, and quality-of-life measures. Safety counts are reported descriptively, without a concurrent comparator or enough detail to establish causation.