A Phase II Study of Androgen Deprivation Therapy With or Without Palbociclib in RB-Positive Metastatic Prostate Cancer: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for A Phase II Study of Androgen Deprivation Therapy With or Without Palbociclib in RB-Positive Metastatic Prostate Cancer (NCT02059213), a randomized phase 2 study. The primary outcome is Number of Patients Who Achieve a PSA ≤ 4ng/mL After Seven Months of Protocol Treatment in Each Arm.

2. Clinical Question

3. Trial Design

This was a randomized, open-label, parallel-group phase II study registered as NCT02059213. Its official title describes a randomized study of ADT with or without palbociclib in RB-positive metastatic hormone-sensitive prostate cancer. The registry record lists prostate cancer as the condition and University of Michigan Rogel Cancer Center as the sponsor. The study is marked completed.

One group received ADT alone; the other received ADT plus Ibrance® (palbociclib). The ADT descriptions specify bicalutamide and either Zoladex or Lupron Depot. For the combination arm, the record describes Ibrance® 125mg by mouth daily on days 1-21 of a 28 day cycle, in addition to ADT. The trial was unmasked, so participants and study personnel were not blinded according to the registry record.

The registry records 72 enrolled patients and 62 randomized patients. Before randomization, the record reports that seven patients did not have adequate tissue for retinoblastoma testing, two tested negative for retinoblastoma, and one had small cell metastasis rather than adenocarcinoma. The full account of who contributed to each outcome analysis is not reported in the registry record. In particular, the primary outcome description is incomplete after noting 60 randomized patients, so the analysis population and handling of missing outcome data cannot be reconstructed fully.

The listed primary outcome timeframe is 28 weeks, and its description refers to PSA measured after seven months of protocol treatment. The registry lists secondary outcomes that include duration of therapy, undetectable PSA, progression-free survival, adverse events, and treatment modifications. The record does not report the rationale for the planned enrollment, details of randomization, or a complete statistical analysis plan.

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: 72 patients were enrolled to the trial. Seven patients did not have adequate tissue for testing retinoblastoma status. Two patients tested negative for retinoblastoma and one patient was found to have small cell metastasis and not adenocarcinoma. 62 patients were randomized.

Overall Study

Analysis population for the primary outcome, as defined in the registry: 72 patients were enrolled to the trial. Seven patients did not have adequate tissue for testing retinoblastoma status. Two patients tested negative for retinoblastoma and one patient was found to have small cell metastasis and not adenocarcinoma. 62 patients were randomized. 60 randomized patients initiated therapy on trial.

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: 62 out of 72 patients enrolled had adequate tissue for RB assessment and retained RB expression. (60 patients initiated treatment.)

6. Primary Endpoint

The registry lists the primary outcome as Number of Patients Who Achieve a PSA ≤ 4ng/mL After Seven Months of Protocol Treatment in Each Arm, measured over 28 weeks.

The primary endpoint counts patients who achieved PSA ≤ 4ng/mL after seven months of protocol treatment. PSA is a laboratory measure used in prostate cancer care; in this trial, the registry specified a threshold and time point so that a response could be classified for each participant. The outcome is binary at the patient level: each participant either met the stated threshold at the assessment or did not. The posted result is therefore a count in each arm, rather than a mean PSA value or a measure of how far each patient’s PSA changed.

Using a defined threshold gives a direct way to compare the proportion of participants meeting a criterion between randomized groups. It also discards information about the magnitude of PSA values within each category: patients with values well below the threshold are counted in the same category. The registry describes the endpoint as an assessment of the proportion achieving PSA below the threshold, while the title states PSA ≤ 4ng/mL. The exact operational handling of a value equal to the threshold is not further explained in the registry record.

The posted counts were 16 of 20 for ADT alone and 32 of 40 for ADT plus Ibrance®. The recalculated unadjusted risk difference is 0.0, with a confidence interval from -0.215 to 0.215. This describes the observed contrast and its uncertainty under the recalculation method; it does not establish equivalence. The registry record does not report a prespecified equivalence or non-inferiority margin for this endpoint.

7. Results Posted in the Registry

• ADT + Ibrance®: 80.0% (32/40) versus 80.0% (16/20) on control; risk difference 0.0 percentage points (95% CI -21.5 to 21.5), risk ratio 1.00 (0.76–1.31); unadjusted two-proportion z-test p = 1.000.

8. Secondary Efficacy Endpoints

The registry also posts results for secondary outcomes. For each outcome below, the endpoint type, the test applied to the posted summary statistics, the result and its interpretation are given in turn. Secondary endpoints are usually not adjusted for multiple testing, so they support rather than confirm the primary finding.

Duration of Therapy

• Endpoint type: Continuous: a mean value per participant, compared as a difference in means.
• Test: Unadjusted two-sample z-test for the difference in means, using the posted standard deviations.
• Result:
  • ADT + Ibrance®: mean 22.00 versus 22.40 on control; difference -0.40 (95% CI -7.56 to 6.76), standardized effect d = -0.03; z-test p = 0.913.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between ADT + Ibrance® and the control. The interval gives the range of effects that remain compatible with the data.

Proportion of Patients Who Achieve Undetectable PSA (<0.2ng/mL)

• Endpoint type: Binary: the number of participants with the event, compared as proportions.
• Test: Unadjusted two-proportion z-test, with a Wald 95% confidence interval for the risk difference.
• Result:
  • ADT + Ibrance®: 55.0% (22/40) versus 65.0% (13/20) on control; risk difference -10.0 percentage points (95% CI -36.0 to 16.0), risk ratio 0.85 (0.55–1.30); unadjusted two-proportion z-test p = 0.459.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between ADT + Ibrance® and the control. The interval gives the range of effects that remain compatible with the data.

The secondary outcomes add breadth to the registry’s account, but the posted numerical results cover only duration of therapy and the proportion achieving undetectable PSA. Those outcomes provide different kinds of information from the primary PSA threshold: one describes time on treatment, while the other uses a lower PSA criterion over a longer stated timeframe. Their estimates do not form a single consistent measure of benefit or harm, and they do not alter the primary endpoint’s definition.

Across the available secondary comparisons, the posted analyses do not report statistically small p-values, and the recalculated contrasts have uncertainty that includes no difference. This broad pattern is compatible with the limited precision of the trial and should not be converted into a claim that all outcomes were identical. The secondary outcomes also differ in measurement, timeframe, and analysis method, so treating them as interchangeable replications of the primary endpoint would be inappropriate.

The registry lists additional secondary outcomes, including progression-free survival, adverse events, and treatment delays or modifications. Numerical results for those outcomes are not reported in the registry record. Their absence limits any overall synthesis of secondary findings. It is not possible to infer their direction or magnitude from the outcome names alone.

Multiple outcome testing matters because, in general, the chance of at least one apparently unusual result can rise when many hypotheses are tested. Adjustments, prespecified outcome hierarchies, or a clearly exploratory interpretation can address this concern in different ways. The registry record does not report a multiplicity adjustment or a hierarchy for these secondary outcomes. Accordingly, unadjusted secondary results carry less confirmatory weight than a prespecified primary analysis, and any patterns should be treated as descriptive rather than definitive evidence.

Secondary outcomes registered for this trial, for reference (only those above were recalculated):

• Number of Participants With Grade >=3 Adverse Events That Are Possibly, Probably or Definitely Related to Study Treatment
• Duration of Therapy
• Proportion of Patients Who Achieve Undetectable PSA (<0.2ng/mL)
• Biochemical Progression-free Survival Rate
• Clinical Progression-free Survival Rate
• Frequency of Dose Modification
• Frequency of Treatment Delay

9. Statistical Interpretation

10. Statistical Methods Explained

What does a binary endpoint comparison estimate?

The primary endpoint records whether each patient did or did not achieve PSA ≤ 4ng/mL at the specified assessment. A group’s event count is interpreted in relation to the number of patients assessed in that group. A risk difference subtracts one group’s event proportion from the other group’s event proportion. In this comparison, the recalculated risk difference is 0.0. A value of zero means the observed proportions are the same in the posted summaries; it does not show that all possible underlying group differences are zero.

Binary outcomes can also be compared with ratios, such as a risk ratio or odds ratio. These express the contrast on different scales, and their values should not be treated as interchangeable. The posted primary comparison includes a risk difference and ratio estimates. The risk difference is often useful for describing an absolute contrast, while ratios describe relative contrasts. The choice of scale affects how an effect is communicated, but none removes the uncertainty caused by limited observations.

Why use Fisher’s exact test?

The registry identifies Fisher Exact as the method for its primary comparison. In general, Fisher’s exact test evaluates the association between group assignment and a binary outcome using the observed counts. It is commonly used when counts are small, because it calculates a probability from the possible allocations of those counts under a null hypothesis. The registry reports p=0.87 for this test. A p-value describes how unusual the observed data, or data more extreme under the test’s definition, would be if the null model held. It is not the probability that the null hypothesis is true and does not measure clinical importance.

The separate recalculated comparison is an unadjusted calculation from the posted summary counts and yields p=1.0. The registry’s p-value and this recalculated value are not identical. The registry record does not explain the difference in analytic details, so they should be presented as separate results rather than treated as if one were a transcription of the other. The sponsor’s reported analysis remains the registry-reported result; the recalculation is a transparent secondary description based on the posted summaries.

What does a confidence interval add?

A confidence interval communicates uncertainty around an estimate. In general, it is produced by a method that would cover the target parameter at a stated rate over repeated samples if the method’s assumptions held. It is not a range containing every plausible value with certainty, and it is not a probability statement about this one interval. For the primary risk difference, the interval runs from -0.215 to 0.215. It includes zero and allows contrasts in either direction. Its breadth signals that the observed counts do not pin down the underlying contrast precisely.

How are continuous outcomes handled?

Duration of therapy is reported as a mean and standard deviation in each arm. A mean summarizes the central value, and a standard deviation describes the spread of individual observations around that mean. The posted arm summaries are 22.4 months with standard deviation 13.1 for ADT alone and 22.0 months with standard deviation 13.8 for ADT plus Ibrance®. The registry reports a two-sided t-test for this comparison. In general, a t-test compares means while accounting for sampling variability; its assumptions concern the distribution of observations and the way the groups are sampled. The registry record does not report diagnostic checks or additional modeling details.

A standard deviation is not a confidence interval and does not describe uncertainty in the mean by itself. It describes variation among observations. The recalculated mean difference is -0.4 months, with a confidence interval from -7.559 to 6.759. The registry-reported p-value is 0.92; the simple unadjusted recalculation gives p=0.913. These summaries describe a comparison, not a causal mechanism or a treatment recommendation.

What are the planning illustrations?

The sample-size illustrations use the observed effect as a starting point and examine planning for 100%, 75%, and 50% of that observed effect. The stated assumptions are a two-sided significance level of 0.05, equal allocation between arms, and a normal approximation. The figures describe participants per arm for 80% power and participants per arm for 90% power under those assumptions. They are planning illustrations, not the trial’s original sample-size justification, and they are not observed power. The registry record does not report the original sample-size calculation or its assumptions.

In general, planning for a smaller effect requires a larger study to achieve the same nominal power and significance level, because a smaller signal is harder to distinguish from random variation. The observed effect in a small study can be unstable, so planning directly from it may be optimistic or otherwise unrepresentative. The registry record does not state that these illustrations were used to design the trial.

Why can over-dispersion matter?

For count outcomes, a model may assume that the variability follows a particular distribution. Over-dispersion means the observed variability is greater than that distribution assumes. If ignored, standard errors can be too small and confidence intervals too narrow. This is a general statistical issue; the posted primary outcome is a binary patient count, and the registry record does not report a count-regression model or an over-dispersion assessment for it.

11. Confidence Intervals and Precision

The primary estimate is the recalculated unadjusted risk difference of 0.0, with a confidence interval from -0.215 to 0.215. This interval is centered on the observed equal proportions but is broad enough to include contrasts in both directions. It therefore conveys less certainty about the underlying difference than the single point estimate alone might suggest. The posted counts are 16 of 20 and 32 of 40, so the outcome information comes from groups of limited size.

In general, confidence intervals describe uncertainty under the analysis method and assumptions used. A narrower interval indicates greater precision; a wider interval indicates less precision. Precision is distinct from whether a result crosses a conventional significance threshold. The primary interval includes zero, but that does not show that the arms are equivalent. Equivalence requires a prespecified margin and an analysis designed to evaluate it; such a margin is not reported in the registry record.

The secondary duration comparison also has a wide interval around its recalculated mean difference, from -7.559 to 6.759 months. For undetectable PSA, the recalculated risk difference is -0.1, with an interval from -0.360 to 0.160. These intervals illustrate that secondary estimates also have uncertainty, but their interpretation depends on the outcome definitions and analysis populations. The registry record does not report confidence intervals for every listed outcome.

Confidence intervals are not predictions for an individual patient and do not account automatically for every source of uncertainty. In particular, they do not correct for unreported analysis choices, missing data, or multiple outcome testing unless the methods explicitly do so. The registry record does not report such adjustments for these comparisons.

12. Analyses Reported by the Sponsor

The registry reports a Fisher Exact p-value of 0.87 for the primary comparison of PSA response. The recalculated unadjusted comparison from the posted group counts gives a risk difference of 0.0, a confidence interval from -0.215 to 0.215, and p=1.0. Both p-values are above conventional significance thresholds, but they are results from different analyses and should not be conflated. The registry record does not explain why the sponsor-reported p-value differs from the simple recalculation.

For duration of therapy, the registry reports a two-sided t-test p-value of 0.92, while the simple unadjusted recalculation gives p=0.913. For undetectable PSA, the registry reports a Fisher Exact p-value of 0.50, while the unadjusted recalculation gives p=0.459. The registry record does not provide enough methodological detail to reconcile these paired values. The recalculations use the posted summary statistics and do not replace a fuller analysis based on individual-level data or the sponsor’s analytic procedures.

There is no flagged discrepancy in the registry record. The sponsor-reported analyses and the recalculations can therefore be read as related but distinct summaries. The registry-reported methods and p-values describe the sponsor’s analyses as recorded; the recalculated estimates add unadjusted contrasts and intervals from the posted summaries. Neither set of results should be interpreted as proof of no difference.

13. Multiplicity, Missing Data and Analysis Populations

The registry identifies one primary outcome and seven secondary outcomes. It records five analyses, but a complete statistical analysis plan is not reported in the registry record. The record does not explain whether secondary outcomes were prespecified in a hierarchy, whether any formal multiplicity procedure was used, or how the primary and secondary tests were intended to inform one another.

Multiplicity is the general statistical issue that arises when several hypotheses are tested. Even when no underlying effects exist, testing many outcomes can increase the chance that at least one result appears statistically unusual. Common responses include adjusting significance thresholds, controlling a family-wise error rate, controlling a false discovery rate, or declaring secondary analyses exploratory. Which approach is appropriate depends on the trial’s aims and analysis plan. No such approach is reported for these results, so the posted secondary p-values should be read without assuming that they are adjusted.

Missing-data handling is also not reported in sufficient detail. The record describes 72 enrolled patients, 62 randomized patients, and reasons some enrolled patients did not reach randomization: seven lacked adequate tissue for testing, two tested negative for retinoblastoma, and one was found to have small cell metastasis rather than adenocarcinoma. The primary outcome description is incomplete after it begins to describe the randomized-patient population. The registry does not give a complete account of who was analyzed for each outcome, how missing assessments were treated, or whether participants were analyzed according to randomized assignment.

These distinctions matter because enrollment, randomization, and outcome analysis populations need not be identical. Excluding participants after randomization or omitting unavailable outcomes can affect the interpretation of a comparison, especially if availability is related to prognosis or treatment. That is a general concern, not a claim that such bias occurred in this trial. Without a complete participant flow and analysis description, the extent of any such effect cannot be assessed from the registry record.

The record also does not report interim-analysis procedures, stopping rules, or sensitivity analyses for missing data. Their existence or absence should not be inferred. The available results support a description of posted counts and analyses, but not a full audit of the trial’s analysis decisions.

14. 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: small intestinal obstruction (5.0%), fever (5.0%), general disorders and administration site conditions - other, specify (5.0%), sepsis (5.0%), urinary tract infection (5.0%).

The registry reports serious adverse events for 5 of 20 participants at risk in the ADT-alone group and 7 of 40 at risk in the ADT-plus-Ibrance® group. It reports deaths of 0 and 1, respectively. These are counts from the posted safety summaries, not estimates adjusted for exposure time or differences in follow-up. The registry record does not provide enough detail to determine the timing or duration of individual participants’ exposure for this comparison.

The listed serious-event terms include small intestinal obstruction, fever, general disorders and administration site conditions, sepsis, urinary tract infection, and acute kidney injury. Each listed term is paired with 5.0% in the registry summary. The record’s summary should not be read as establishing that each term was caused by study treatment. The listed safety outcome specifically concerns adverse events considered possibly, probably, or definitely related to study treatment, while the registry does not give detailed case-level assessments in the posted summary.

Safety counts need context: the group sizes differ, and a simple count does not capture event severity, recurrence, timing, or exposure duration. The posted figures describe what was recorded; they do not by themselves establish a comparative safety profile. The registry record does not report a formal statistical comparison of these serious adverse-event counts.

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

The primary comparison describes similar observed proportions of participants meeting the stated PSA threshold in the two randomized groups. The recalculated point estimate is a risk difference of 0.0, but its confidence interval ranges from -0.215 to 0.215. This is a result with substantial uncertainty, not a demonstration that the treatments are equivalent or that the underlying difference is exactly zero.

The result does not establish that adding palbociclib improves the endpoint, nor does it establish that it has no effect. A nonsignificant comparison can occur when the true difference is small, when the study is imprecise, or for other reasons. The registry record does not report a clinically important difference threshold or an equivalence design, so the data cannot be interpreted as a formal test of equivalence.

The trial’s scope also matters. It enrolled a selected group described as RB-positive metastatic hormone-sensitive prostate cancer, and the record documents that some enrolled patients did not proceed to randomization for tissue-testing or disease-type reasons. Conclusions should not be extended automatically to populations not represented by the randomized participants. The complete primary analysis population and handling of missing outcomes are not reported in the registry record.

Secondary outcomes offer further descriptions, but their results are limited and are not a substitute for the primary question. Several listed secondary outcomes have no numerical results reported in the registry record. Unadjusted secondary comparisons are generally less confirmatory when multiple outcomes are considered without a reported multiplicity plan.

In general, a trial result informs an evidence base; it does not itself dictate a clinical decision. The posted data describe this study’s comparisons and uncertainty. They do not provide individual predictions, establish a mechanism, or warrant medical advice.

16. Why This Trial Matters Statistically

This trial illustrates a central statistical distinction: an observed point estimate and the precision around it answer different questions. The primary point estimate is 0.0 on the risk-difference scale, while the interval around it spans contrasts in both directions. Reporting only the point estimate could make the comparison sound more conclusive than the data support; reporting the interval makes the uncertainty visible.

It also illustrates why a non-significant test should not be treated as proof of sameness. The registry-reported primary p-value is 0.87, while the recalculated unadjusted p-value is 1.0. Neither p-value gives the probability that the treatments are equivalent, and the registry record does not report an equivalence margin. The trial can therefore be read as an estimate with uncertainty, rather than as a definitive declaration of no difference.

The enrollment-to-randomization pathway is another important statistical feature. The registry records 72 enrolled and 62 randomized, alongside reasons some patients did not proceed. These details help readers recognize that the population contributing to the randomized comparison may be narrower than the initially enrolled group. Incomplete reporting of the analysis population and missing-data procedures limits assessment of how that pathway affected the outcome estimates.

Finally, the registry offers both sponsor-reported tests and simple recalculations from posted summaries. Differences between them highlight the value of transparent methods and clearly described analysis populations. The results show why careful interpretation depends not only on a p-value, but also on the endpoint definition, group counts, confidence intervals, analysis methods, and limits of the record.

17. 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 principal limitation is imprecision in the primary comparison. The randomized groups contained 20 and 40 participants, and the confidence interval for the recalculated risk difference extends in both directions around zero. The result cannot rule out effects that would matter under some clinical thresholds, because no such threshold is reported in the registry record.

The analysis population is incompletely described. Although the record reports enrollment, randomization, and some reasons for non-randomization, the primary population description is truncated. The number of participants contributing to each outcome and the treatment of missing assessments are not fully reported. This limits assessment of attrition and the possibility of bias from unavailable outcomes.

The study was open-label. That design feature does not automatically invalidate an objective laboratory endpoint, but knowledge of treatment assignment can influence care, co-interventions, follow-up, or decisions about assessments. The registry record does not report procedures to address or assess these possibilities.

The sponsor-reported and recalculated p-values differ for the available comparisons. The record does not give enough detail to reconcile the differences. Individual-level data and a complete statistical analysis plan are not reported, which prevents independent reconstruction of all analytic choices. The registry also does not report the original sample-size justification, interim analyses, or a multiplicity strategy.

Finally, only some secondary outcomes have numerical results in the record. Progression, dose modification, treatment delay, and other listed outcomes cannot be evaluated quantitatively from the information reported. The posted safety summaries also do not provide detailed timing, exposure-adjusted rates, or a formal statistical comparison. These limitations constrain both efficacy and safety interpretation.

18. Related Tutorials

19. Related Statistical Calculators

20. Sources

• ClinicalTrials.gov: A Phase II Study of Androgen Deprivation Therapy With or Without Palbociclib in RB-Positive Metastatic Prostate Cancer — NCT02059213.
• Registry record last updated 2020-09-16; status last verified 2020-08.
• Results first posted 2019-01-28.
• 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.

21. Record Summary

NCT02059213 is a completed randomized, open-label phase II study of ADT alone versus ADT plus Ibrance® (palbociclib) in RB-positive metastatic hormone-sensitive prostate cancer. The registry records 72 enrolled patients and 62 randomized patients. The primary endpoint was achievement of PSA ≤ 4ng/mL after seven months of protocol treatment.

The posted primary counts were 16 of 20 with ADT alone and 32 of 40 with ADT plus Ibrance®. The recalculated unadjusted risk difference was 0.0, with a confidence interval from -0.215 to 0.215; the registry reports a Fisher Exact p-value of 0.87. Available secondary results describe duration of therapy and undetectable PSA, while numerical results for several listed outcomes are not reported in the registry record.

Incomplete reporting of the analysis population, missing-data procedures, sample-size rationale, and multiplicity handling limits interpretation. The results describe the posted comparisons but do not establish equivalence.