Genetic and Molecular Mechanisms in Assessing Response in Patients With Prostate Cancer Receiving Enzalutamide Therapy: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Genetic and Molecular Mechanisms in Assessing Response in Patients With Prostate Cancer Receiving Enzalutamide Therapy (NCT02099864), a na phase 2 study. The primary outcome is Percentage of Participants With Tumor Protein 53 Gene (TP53) Copy Number Alterations and Mutations.

2. Clinical Question

This question links a molecular feature measured in a pretreatment tumor sample with a clinical response measure assessed after treatment begins. The intended comparison is between patients categorized by baseline TP53 status and their PSA response status at 12 weeks. The registry description names an odds ratio with a two-sided 95% confidence interval as a planned summary of that association. It also says that percentages would be reported by arm, although the registered design is single-group; that wording does not establish a control arm.

The study also planned to examine other clinical outcomes and tumor or blood characteristics, including objective response, survival measures, PSA progression, molecular features in tumors progressing during treatment, and circulating tumor cell counts. Those secondary aims provide context for the broader study, but their results are not reported in the registry record. The primary question is therefore about an association within the treated study group, not whether enzalutamide causes a particular molecular or clinical outcome.

3. Trial Design

This is a phase II, single-group study of enzalutamide in patients with prostate cancer. The registry record lists an enrollment of 36 and identifies OHSU Knight Cancer Institute as the sponsor. The study is marked completed. Its listed start date is 2014-02-05, and its primary completion date is 2019-10-01.

The design has no randomized allocation and no masking. A single treatment group received enzalutamide orally once daily, with treatment described as continuing in the absence of disease progression or unacceptable toxicity. The registry record does not describe a contemporaneous untreated group or an active-comparator group. Consequently, any association between TP53 status and PSA response is estimated among participants in this study; the design does not isolate the effect of treatment from other explanations for changes during follow-up.

Biopsy sampling was central to the molecular aim. The treatment description specifies a biopsy of a metastatic site at study entry, before enzalutamide, and another after the time of progression. The primary endpoint description focuses on baseline TP53 copy number alterations and mutations and their association with PSA response at 12 weeks. The record also lists blood sampling-related measures, including changes in circulating tumor cell counts, among the secondary outcomes.

The primary endpoint description says evaluable patients would have genomic and immunohistochemistry data from pretreatment biopsy samples and would have completed at least 12 weeks of therapy or experienced confirmed progression before that point. The number meeting this definition is not reported in the registry record. Nor are the number of participants with usable biopsy results, the number with missing PSA assessments, or the analysis population for each secondary outcome reported. The registry record does not report the sample-size justification, detailed eligibility criteria, or a full statistical analysis plan.

Because the study is single-group, comparisons within the group should not be read as randomized treatment comparisons. The record’s mention of percentages “in each arm” in the primary endpoint description is not consistent with its single-group design listing. This discrepancy in wording does not establish that another arm existed. The record also does not report whether additional analyses used subgroups or adjusted for other participant or tumor characteristics.

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

Analysis population for the primary outcome, as defined in the registry: Evaluable patients will include those patients for whom data from genomic studies and IHC tests are available from the pre-treatment biopsy samples and who have completed at least 12 weeks of therapy or who have confirmed disease progression prior to 12 weeks of therapy, and for whom baseline and 12 week PSA data were available. 36 subjects shown in participant flow. 2 subjects were excluded from this PSA analysis: 1 had missing PSA data, 1 had falling PSA in setting of rapid disease progression

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 Percentage of Participants With Tumor Protein 53 Gene (TP53) Copy Number Alterations and Mutations, measured over Baseline to 12 weeks.

The primary endpoint is titled as the percentage of participants with TP53 copy number alterations and mutations. Its timeframe is baseline to 12 weeks. The endpoint description explains the scientific question as an evaluation of the association between PSA response at 12 weeks after therapy initiation and TP53 copy number alterations and mutations measured at baseline.

In general, a percentage expresses how common a specified characteristic is in a defined group. Here, TP53 status is a tumor feature intended to be assessed using pretreatment biopsy material. PSA response is the clinical response classification used for the association analysis. The registry record does not state the threshold or rule used to classify PSA response, nor does it report the resulting percentages or association estimate.

This type of endpoint is used to ask whether a baseline molecular feature distinguishes participants with different observed response categories. It is not, by itself, a test of whether TP53 alterations cause a response, nor does an association establish that the molecular feature predicts treatment benefit compared with another treatment. Such a treatment-comparative claim would require a suitable comparison and analysis; this study is listed as single-group.

The endpoint description says simple logistic regression was planned, but that Fisher’s Exact test was used due to sample size. It also describes calculating an odds ratio with a two-sided 95% confidence interval. The actual analysis results, including the estimate, interval, and statistical significance, are not reported in the registry record. Without those results, the strength and precision of the association cannot be assessed.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry endpoint description states that simple logistic regression was planned, but Fisher’s Exact test was used due to sample size. It also describes reporting percentages and calculating an odds ratio with a two-sided 95% confidence interval. The record does not provide the primary analysis output, so these methods can be explained as statistical approaches rather than as evidence about the study’s findings.

What does an association analysis ask?

In general, an association analysis examines whether two measured characteristics occur together more or less often than would be expected if they were unrelated. In this study’s stated question, one characteristic is TP53 copy number alteration or mutation status at baseline, and the other is PSA response at 12 weeks. The analysis would compare response patterns across categories of baseline TP53 status. An association is descriptive of the analyzed participants and does not, on its own, demonstrate causation.

Why was logistic regression planned?

In general, logistic regression is used when an outcome is classified into two categories, such as response versus no response. It models the relationship between that outcome and one or more explanatory variables. A simple logistic regression uses one explanatory variable at a time, while a model with multiple variables can adjust for other measured characteristics. The registry description says simple logistic regression was planned. It does not report a final regression model, covariates, diagnostics, or an adjusted estimate.

An odds ratio is a way to express the relationship between two binary classifications. In general, it compares the odds of the outcome across groups. Its interpretation depends on how the outcome and groups are coded, and a value alone does not describe the uncertainty around the estimate. The registry record says an odds ratio was to be reported, but the estimate and the coding details are not reported. No numerical interpretation of the association is possible without those details and the result.

Why use Fisher’s Exact test?

In general, Fisher’s Exact test evaluates whether two categorical variables are associated in a contingency table. It is useful when sample sizes or cell counts are small because it calculates probabilities using the observed margins rather than relying on a large-sample approximation. Sparse data can make estimated associations unstable and confidence intervals wide. The registry description says Fisher’s Exact test was used due to sample size, but it does not provide the table counts or the test result. Therefore, the degree of sparsity and its effect on precision cannot be assessed from the record.

The record’s stated reason for changing from the planned regression approach is sample size. It does not provide a threshold for that decision, a detailed account of the analysis process, or information about whether the switch was made before or after examining the data. Those details are not reported in the registry record. The choice of test does not itself indicate whether the result was statistically significant or clinically meaningful.

What does a 95% confidence interval communicate?

In general, a confidence interval represents uncertainty around an estimated quantity under the model and sampling procedure used. For an odds ratio, the interval gives a range of values compatible with the data and assumptions. A wider interval reflects less precision. It is important to read the interval with the point estimate and the study design, rather than treating a confidence interval as a guarantee that the true value lies within a particular range. The registry describes a two-sided 95% interval but does not report its endpoints.

For this study, the effective information for the primary association depends not only on total enrollment, but also on how many participants had usable baseline samples and response assessments, and how observations were distributed across categories. A small count in any category can reduce the information available for estimating an association. The registry record does not report these counts, so the precision cannot be reconstructed from enrollment alone.

How should planning illustrations be read?

In general, a sample-size calculation translates assumptions about a target effect, significance level, allocation, and statistical method into a planning quantity. It is not a measure of the probability that a completed study detected an effect. The registry record’s stated planning assumptions describe a two-sided significance level of 0.05, equal allocation between two arms, a normal approximation, and target effects expressed as fractions of an observed effect. Those assumptions are not the registered single-group design, and the description labels the calculation as a planning illustration rather than the trial’s own design.

Such illustrations should not be interpreted as observed power or as proof that the study was adequately sized. In general, observed power calculated from an observed effect is not a substitute for examining the estimate and its confidence interval. The registry record does not report the original sample-size justification or enough primary endpoint results to assess precision directly. Statistical significance, if reported, would also not by itself establish the size or importance of an association.

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("Responders", "PSA Non-responders")
n      <- c(21, 5)
events <- c(6, 4)
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  Responders  21  6  28.6  11.3  52.2  13.8  50.0  13.9  50.2
ARM  PSA Non-responders  5  4  80.0  28.4  99.5  37.6  96.4  35.9  95.7

11. Multiplicity, Missing Data and Analysis Populations

The study lists multiple secondary outcomes, including PSA changes, objective response, progression-free survival, disease-specific survival, overall survival, PSA progression, tumor molecular features during progression, and circulating tumor cell counts. The registry record also reports 20 outcome measures and 12 analyses. It does not report a multiplicity adjustment, a hierarchy for testing endpoints, or a plan distinguishing confirmatory from exploratory analyses. The number of outcomes alone does not establish how many statistical tests were conducted or how they were interpreted.

In general, testing multiple hypotheses can increase the chance of observing at least one apparently notable result by chance. A prespecified hierarchy or adjustment can address that issue, while clearly labeling analyses as exploratory helps readers interpret a broad set of results. Since the analysis plan and outcome results are not reported in detail, it is not possible to determine how multiplicity was handled or whether findings were selected for reporting.

Missing data are particularly relevant to the primary endpoint because the stated evaluable population required genomic and immunohistochemistry data from a pretreatment biopsy, as well as sufficient follow-up or confirmed progression before 12 weeks. The number excluded for unavailable or inadequate samples, missing response measurements, or other reasons is not reported in the registry record. The handling of missing values and the assumptions behind that handling are also not reported.

The registry record does not give the analysis population for each outcome, the number assessed at each time point, or whether participants were analyzed according to a prespecified intention-to-treat or evaluable-patient approach. The description of the primary endpoint defines an evaluable population, but it does not provide a participant flow or a count for that population. These omissions limit assessment of selection effects and the representativeness of the analyzed participants. The record does not report sensitivity analyses for missing data or alternative analysis populations.

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: urinary tract infection (5.6%), fracture (2.8%), acute kidney injury (2.8%), anemia (2.8%), atrial fibrillation (2.8%).

For the enzalutamide group, the registry record lists 36 participants at risk for serious adverse events and 6 affected. It lists 36 participants at risk for other adverse events and 36 affected, and records 2 deaths. These are safety summaries, not randomized comparisons. The record does not establish that an event or death was caused by enzalutamide.

The listed serious adverse-event terms and percentages are urinary tract infection, 5.6%; fracture, 2.8%; acute kidney injury, 2.8%; anemia, 2.8%; atrial fibrillation, 2.8%; and myelodysplastic syndrome, 2.8%. These percentages should be read as the registry’s reported values, not as estimates of comparative risk. The record does not provide event timing, severity grades, exposure duration, or causal attribution for these terms.

In general, a participant count affected is not necessarily the same as a count of all event occurrences, because one participant may experience more than one event. The record does not explain whether the serious-event terms refer to unique participants or event counts. The listed figures therefore describe the posted safety summary but do not support a detailed comparison of risks. A control group and more complete event-level information are not reported in the registry record.

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

The study’s primary statistical aim is to examine whether baseline TP53 copy number alterations and mutations are associated with PSA response at 12 weeks among patients receiving enzalutamide. This is a molecular-response question within a single treatment group. It is distinct from a trial designed to compare treatment outcomes between enzalutamide and another option.

The registry record identifies how the primary analysis was intended to be summarized, but does not report the estimate, confidence interval, test result, category counts, or percentage of participants with TP53 alterations. As a result, the posted record does not establish whether the characteristics were associated, the direction of any relationship, or the degree of uncertainty. It also does not report the primary endpoint’s observed result in enough detail to interpret its magnitude.

Even if an association were reported, it would not establish that TP53 status causes PSA response or that the status identifies who benefits specifically from enzalutamide. The single-group design cannot separate an association observed during treatment from one that might also occur without treatment or with a different treatment. In general, demonstrating treatment-specific predictive value requires an appropriate comparison and analysis, neither of which is described as part of this single-group design.

The trial also planned to assess survival, objective response, PSA progression, tumor changes, and circulating tumor cell counts. The registry record does not report those findings. Likewise, the safety summary records adverse-event observations but does not establish causality or comparative safety.

Thus, the record supports a description of the study question, planned molecular sampling, and selected safety counts. It does not support a conclusion about the primary association, treatment benefit, or comparative safety. The absence of reported endpoint results is an important interpretive limit, rather than evidence that no association or outcome occurred.

14. Why This Trial Matters Statistically

This trial is statistically notable for connecting a baseline molecular measurement with a response classification measured after treatment begins. That structure raises practical questions about sample availability, endpoint definition, and how a small number of observations may be distributed across categories. The registry’s stated shift from simple logistic regression to Fisher’s Exact test due to sample size makes the choice of method especially relevant to interpretation.

In general, small or sparse data can make model estimates unstable and leave substantial uncertainty, even when a test can be calculated. A method suited to small categorical datasets can address some limitations of large-sample approximations, but it cannot create information that is absent from the data. Reporting category counts and an interval around the association would be important for understanding both the result and its precision. Those primary analysis details are not reported in the registry record.

The study also illustrates the difference between a molecular association question and a treatment-effect question. A single-group analysis may describe which tumor features occur alongside response among treated participants, but it cannot establish whether those features modify the effect of treatment relative to a comparator. The distinction is central when interpreting biomarker analyses.

Finally, the registry identifies numerous secondary outcomes and analyses, while the detailed multiplicity approach and outcome results are not reported. Clear reporting of analysis populations, missing samples, outcome definitions, and uncertainty would be needed to judge how robustly the molecular question was answered. The record makes the intended question visible, but does not report the results required to assess its statistical resolution.

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 important trial-specific limitation in the registry record is the absence of reported results for the primary endpoint. No observed TP53 percentages, PSA-response counts, odds ratio, confidence interval, or test result are reported. The proposed association therefore cannot be evaluated for direction, magnitude, or precision.

The listed enrollment is 36, but the number of participants included in the primary analysis is not reported. The endpoint’s evaluability criteria depend on pretreatment genomic and immunohistochemistry data and follow-up or progression status. Without counts for available biopsies, completed assessments, exclusions, or missing observations, the impact of sample availability on the analysis cannot be assessed.

The single-group, unmasked design does not provide a randomized control comparison. Any association within the treated group would not establish a treatment-specific biomarker relationship, and the design does not support a controlled estimate of treatment effect. The registry record does not report adjustment for potential confounding factors or the details of the response classification.

The primary endpoint description refers to percentages “in each arm,” although the registered design is single-group. The record does not clarify this wording. The description also notes a change from planned logistic regression to Fisher’s Exact test due to sample size, but does not report when or how that decision was made, the category counts, or the final analytic details.

Other limitations include the absence of detailed missing-data procedures, multiplicity methods, outcome-specific analysis populations, and secondary outcome results. The safety information is limited to selected summary figures and does not report event timing or causal attribution. These limits apply to what can be assessed from the registry record; they do not establish that additional analyses or information do not exist elsewhere.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Genetic and Molecular Mechanisms in Assessing Response in Patients With Prostate Cancer Receiving Enzalutamide Therapy — NCT02099864.
• Registry record last updated 2024-09-19; status last verified 2024-09.
• Results first posted 2021-01-13.
• 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

NCT02099864 is a completed phase II, single-group study sponsored by OHSU Knight Cancer Institute. The registry record lists an enrollment of 36, with enzalutamide given orally once daily. The study focused on molecular mechanisms in prostate cancer, including the association between baseline TP53 alterations and PSA response at 12 weeks.

The registry describes a plan for simple logistic regression, with Fisher’s Exact test used due to sample size, and an odds ratio with a two-sided 95% confidence interval. The primary endpoint results and detailed analysis population are not reported in the registry record. Several clinical and molecular secondary outcomes are listed, but their results are also not reported in the registry record.

The record lists serious adverse events affecting 6 of 36 participants, other adverse events affecting 36 of 36, and 2 deaths. Those figures do not establish causality or comparative safety. The single-group design does not provide a randomized treatment comparison.