Phase II Trial of Palbociclib in Patients With Metastatic Urothelial Cancer After Failure of First-Line Chemotherapy: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Phase II Trial of Palbociclib in Patients With Metastatic Urothelial Cancer After Failure of First-Line Chemotherapy (NCT02334527), a na phase 2 study. The primary outcome is Progression Free Survival.

2. Clinical Question

This is a focused question about a fixed-time status in a biomarker-defined clinical setting. The biomarkers in the brief summary—CDKN2A loss and positive Rb expression—describe the intended study population, not a result about whether a participant responded. The record does not report how the biomarker findings were established, how many participants met each criterion, or whether outcomes were analyzed by biomarker status.

Because the trial has a single treatment group, its primary question is descriptive: what was the 4-month progression-free survival estimate in the studied group? Without a control group, differences that might have occurred under another treatment or under no study treatment cannot be estimated from this trial alone. The registry lists secondary outcomes of progression-free survival, overall survival, response rate, and adverse events, but does not report their results.

3. Trial Design

The registry describes a phase II, multicenter, single-group study of palbociclib in metastatic urothelial cancer after failure of first-line chemotherapy. Enrollment is listed as 12. The record identifies the study status as terminated. It does not report the reason for termination, so the status alone does not establish why the study ended or what effect termination had on data collection.

There is no randomized allocation or control arm in the record: allocation is NA, the model is single-group, and masking is none. These features mean that the study is not a randomized comparison. Any outcome in the palbociclib group therefore describes participants in that group; it cannot isolate a treatment effect from other influences by comparing concurrent groups.

The primary endpoint is progression-free survival at 4 months. The registry defines it as the percentage of patients alive and free from progression at that time. Listed secondary outcomes include progression-free survival, overall survival, response rate based on complete or partial response, and adverse events. The record identifies five outcome measures, but it does not provide analysis records for them.

The brief summary describes the intended population as patients with metastatic urothelial carcinoma with CDKN2A loss and positive Rb expression after first-line chemotherapy. The record does not report a detailed eligibility flow, the number screened, the number treated, or analysis populations. Nor does it describe the statistical plan, sample-size justification, interim analyses, or procedures for assessing progression. Those details are not reported in the registry record.

For interpretation, it is important to distinguish the trial design from planning illustrations based on hypothetical comparisons. A single-group study does not contain the two randomized arms assumed in the registry’s planning note. Such planning calculations cannot turn the observed single-group experience into a controlled treatment comparison.

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: 34 patients were screened, 25 were eligible based on tumor immunohistochemistry (IHC) demonstrating p16 loss and intact retinoblastoma. Of those, 12 patients were enrolled.

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 Progression Free Survival, measured over 4 Months.

The primary endpoint is progression-free survival at 4 months. As defined in the registry, it is the percentage of patients who are alive and free from progression at 4 months. It combines two ways of not remaining progression-free: progression of cancer or death before the specified time. It is a status at a fixed time, rather than a direct description of how long each participant remained free from progression.

A fixed-time progression-free survival estimate can provide a clinically interpretable snapshot of disease status at a stated follow-up point. In general, it can be useful when a study seeks to describe whether participants remain alive without documented progression at a particular landmark. It does not, by itself, explain when progression or death occurred, how outcomes unfolded before the landmark, or which component drove the result.

The registry record does not report the 4-month estimate, its confidence interval, the number of participants evaluable at that time, or how progression and censoring were assessed. The enrollment field alone does not establish how many participants contributed to the primary endpoint analysis. Without those details and the result, the endpoint definition can be described, but the primary outcome cannot be interpreted quantitatively.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

Statistical interpretation begins with the distinction between an endpoint definition and an endpoint result. The definition says what is to be measured: here, the percentage of patients alive and free from progression at 4 months. A result would additionally state the observed estimate and usually describe its uncertainty. The registry record gives the definition but not the estimate or its uncertainty, so no quantitative conclusion about the endpoint follows from the definition alone.

What does a fixed-time progression-free survival estimate represent?

In general, a fixed-time estimate describes the probability or proportion of remaining alive without progression through a specified follow-up point. It brings progression and death together in a single endpoint. That can make a result easier to communicate as a status at a clinically chosen time, but it does not show the separate contribution of progression and death. Nor does it summarize the full pattern of event times as completely as a time-to-event curve may do.

Time-to-event analyses can account for participants whose event status is not observed through the full follow-up, using censoring methods under stated assumptions. Censoring means that a participant’s event time is not known beyond the last time they were observed event-free. The validity of an estimate depends on how follow-up and censoring are handled and on assumptions about why observation ended. The statistical method, censoring rules, and follow-up details are not reported in the registry record. It is therefore not possible to determine how the 4-month endpoint was estimated or whether all participants had sufficient follow-up.

Why does uncertainty matter?

A confidence interval is a statistical range expressing the uncertainty around an estimate under the method’s assumptions. In general, a wider interval indicates less precision, while a narrower interval indicates greater precision. The interval is not a guarantee that the true value lies within its limits, and it does not remove possible bias from study design or measurement. No confidence interval for the primary endpoint is reported in the registry record, so the precision of the intended estimate cannot be judged.

For a simple binary outcome, uncertainty depends in part on the number of participants with observed outcome information and the number experiencing the event of interest. But the primary endpoint is described as a fixed-time progression-free survival measure, and the registry does not report the relevant analysis denominator, event counts, or method. It would be inappropriate to reconstruct an estimate or interval from enrollment alone. The safety counts cannot be substituted for progression and death information used in the primary endpoint.

How should the single-group design affect interpretation?

A single-group design estimates outcomes among people receiving the study intervention, subject to the study’s eligibility criteria, follow-up, and measurement procedures. It does not directly estimate what would have happened to comparable participants receiving a different intervention. Randomized concurrent controls can help balance measured and unmeasured prognostic factors on average; that protection is absent when the registry lists no comparator and no random allocation. Historical expectations or external comparisons would require additional data and assumptions, neither of which is reported in the registry record.

The lack of masking also matters in general. Knowledge of treatment assignment can influence subjective assessments, decisions about additional care, reporting of symptoms, or timing of evaluations. The record identifies masking as none, but does not describe outcome-assessment procedures. This does not show that the endpoint assessment was biased; it identifies a design feature that readers should consider alongside the missing details.

What do planning calculations mean?

Sample-size calculations are planning tools: they describe how many participants or events might be needed under specified assumptions to detect a chosen effect with a chosen statistical error rate. They are not observed power, and they do not establish whether an observed result is reliable. The registry’s planning note describes a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation, with the effect set as a stated fraction of an observed effect. It also distinguishes event totals for time-to-event outcomes from participants per arm for other outcomes.

Those assumptions describe hypothetical planning calculations and do not match the registered single-group design. The registry record does not report the numerical planning outputs or the trial’s own sample-size justification. It also does not report an observed primary effect from which to assess those illustrations. Thus, planning calculations should not be read as a claim that this study had a particular power, nor as evidence that it reached a prespecified target.

Why can over-dispersion matter?

In general, over-dispersion occurs when observed variation in count data exceeds what a simple model assumes. If it is ignored, standard errors can be too small and confidence intervals too narrow, making results appear more precise than warranted. Appropriate modeling depends on the outcome distribution, study design, and analysis plan. The primary endpoint is described as a participant-based progression-free survival measure, and the registry does not state that a count model or an over-dispersion adjustment was used. This general issue should not be taken to imply that over-dispersion affected this study.

Overall, the methods needed to reproduce or fully evaluate the primary analysis—including the estimator, handling of censoring, analysis population, and uncertainty calculation—are not reported in the registry record. General statistical principles clarify what such details would mean, but they cannot supply a missing result or recover an undocumented analysis.

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 (Single Arm Trial)")
n      <- c(12)
events <- c(2)
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 (Single Arm Trial)  12  2  16.7  2.1  48.4  4.7  44.8  5.0  45.4

11. Multiplicity, Missing Data and Analysis Populations

The registry lists several outcomes: progression-free survival, overall survival, response rate based on complete or partial response, and adverse events. When a study evaluates multiple outcomes, multiplicity can arise if researchers conduct several statistical tests and interpret them as independent opportunities for evidence. In general, multiple testing can increase the chance of at least one apparently noteworthy result unless the analysis plan addresses that issue. The registry record does not report a multiplicity strategy, a hierarchy of endpoints, or which outcomes were intended for confirmatory inference.

The record identifies five outcome measures and reports no analysis records. This does not establish whether analyses were conducted elsewhere; it means that outcome analyses are not reported in the registry record. No outcome-specific estimates, test results, or analysis populations are available in the record for interpreting multiplicity or distinguishing planned from exploratory analyses.

Missing-data handling is also not reported. For the fixed-time primary endpoint, interpretation would depend on follow-up through 4 months and on how participants without observed progression status at that time were handled. The registry does not report censoring rules, reasons for loss to follow-up, or how missing assessments were treated. Enrollment cannot be assumed to equal the number with complete endpoint information.

The record does not identify an intention-to-treat, treated, or evaluable analysis population, and it does not explain exclusions or deviations from eligibility. These are not merely reporting details: the population included in an analysis helps define what the estimate represents. Without the analysis population and missing-data procedures, neither the denominator nor the potential influence of incomplete follow-up can be assessed.

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: confusion (8.3%), diarrhea (8.3%), fall (8.3%), hyperkalemia (8.3%), small intestinal obstruction (8.3%).

The registry lists 3 participants with serious adverse events among 12 at risk, and 12 participants with other adverse events among 12 at risk. It separately lists 11 deaths. These entries should be read as the registry’s recorded safety counts; the record does not report the observation period, timing, causes of death, or whether deaths overlapped with the serious adverse event count.

The listed serious adverse event terms are Confusion, Diarrhea, Fall, Hyperkalemia, and Small intestinal obstruction, each reported at 8.3%. The record does not provide a denominator alongside these term percentages or explain whether participants could contribute more than one term. The percentages therefore should not be added together or treated as mutually exclusive categories.

These figures do not establish that palbociclib caused an event. The registry does not report attribution, event-level detail, severity grades, duration, or a comparison group. Counts of participants with an event are also different from counts of event episodes: a participant may have experienced more than one event, but the record does not describe that pattern. The safety information is useful as a record of reported counts and terms, but it is insufficient for a comparative assessment or a causal conclusion.

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

The registry record establishes that a phase II study evaluated palbociclib in a single group of patients with metastatic urothelial cancer after failure of first-line chemotherapy. Its brief summary specifies CDKN2A loss and positive Rb expression as population features. The primary endpoint was defined as progression-free survival at 4 months. These details identify the clinical setting and the question the study was intended to address.

The record does not report the primary endpoint result. It also does not report outcome estimates for the listed secondary endpoints. As a result, the registry information cannot show the observed level of progression-free survival at 4 months, the precision of an estimate, or how outcomes varied across participants. No claim that the treatment did or did not produce benefit follows from the endpoint definition or study status.

The study’s single-group design places a further limit on interpretation. An outcome observed in the palbociclib group would not, by itself, establish what would have happened to comparable patients under another treatment. The absence of randomization and a comparator means that causal contrasts are unavailable from this record. The status of terminated does not identify the reason the study ended; that reason is not reported in the registry record.

The safety entries document reported participant counts, deaths, and serious adverse event terms, but they do not establish attribution to treatment or comparative risk. Their interpretation is constrained by missing information on timing, analysis population, observation period, and overlap among categories. They should not be used as a substitute for the missing efficacy outcomes.

In general, a clinical trial record can describe a planned question, design features, and recorded outcomes while still leaving substantial uncertainty about results and methods. Here, the central quantitative efficacy result and key analysis details are not reported. The record can therefore support a description of what was studied and how it was registered, but not a conclusion about efficacy, comparative effectiveness, or causation.

14. Why This Trial Matters Statistically

This trial is statistically instructive because its primary question is stated in a concrete way: progression-free survival at 4 months in a defined clinical setting. A fixed-time endpoint is readily interpretable as a status at a particular follow-up point, but its usefulness depends on seeing the estimate, uncertainty, and information about follow-up. Those results and details are not reported in the registry record.

The record also illustrates why study design determines the kinds of conclusions that are possible. With a single treatment group and no registered comparator, an outcome describes the study group but does not provide a randomized contrast. Even a precise estimate would not, by itself, address what outcomes would have been under an alternative treatment. Statistical precision and causal interpretation are separate issues: greater precision cannot replace a control group.

Enrollment is listed as 12, which makes transparent reporting of analysis populations and follow-up especially important for understanding what information underlies an estimate. The registry does not report how many participants contributed to the primary endpoint, how missing follow-up was handled, or the uncertainty around an estimate. Without those details, readers cannot determine whether a result—if reported elsewhere—would be precise or sensitive to incomplete observation.

Finally, the terminated status and safety entries underscore the value of reporting outcomes and methods together. Status alone does not explain why the study ended, and safety counts alone do not establish causation. The record’s gaps show how endpoint definitions, analysis plans, denominators, and results work together to make trial evidence interpretable.

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 registry record does not report the primary progression-free survival result, its confidence interval, or the number included in its analysis. It also does not report the results of the listed secondary outcomes. This prevents quantitative assessment of efficacy outcomes and their precision.

The single-group design has no concurrent comparator, and allocation is listed as NA. The study is unmasked. These design features limit comparative and causal interpretation. The record does not report outcome-assessment procedures, progression criteria, or whether assessments were independently reviewed.

The registry lists enrollment as 12, but does not report how many participants were screened, treated, followed to 4 months, or included in each analysis. Eligibility flow, missing-data methods, censoring rules, and analysis populations are not reported in the registry record. The biomarker-defined population is described in the brief summary, but the record does not give participant-level biomarker counts or outcomes by biomarker status.

The study status is terminated, but the reason, timing relative to outcome collection, and implications for follow-up are not reported. The statistical plan, sample-size justification, interim analyses, and multiplicity approach are also not reported in the registry record. The safety entries lack detail on attribution, timing, event overlap, and causes of death. Together, these limitations mean that the record documents the study’s registered question and design, but leaves key information needed to assess outcome estimates and their interpretation unavailable.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Phase II Trial of Palbociclib in Patients With Metastatic Urothelial Cancer After Failure of First-Line Chemotherapy — NCT02334527.
• Registry record last updated 2018-11-16; status last verified 2018-11.
• Results first posted 2018-04-24.
• 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 describes a terminated, multicenter phase II, single-group study of palbociclib in metastatic urothelial cancer after failure of first-line chemotherapy. The brief summary specifies CDKN2A loss and positive Rb expression. Enrollment is listed as 12; masking is none, and no comparator arm is registered.

The primary endpoint is progression-free survival at 4 months, defined as the percentage alive and free from progression. The registry record does not report its result or uncertainty. It lists secondary outcomes including progression-free survival, overall survival, response rate, and adverse events, but no analyses are reported in the registry record.

Safety entries list 3 participants with serious adverse events, 12 with other adverse events, and 11 deaths. The reason for termination and key statistical and missing-data methods are not reported. The record supports a description of the study design, but not a quantitative efficacy conclusion or a controlled treatment comparison.