A Study of Apalutamide (ARN-509) in Men With Non-Metastatic Castration-Resistant Prostate Cancer: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for A Study of Apalutamide (ARN-509) in Men With Non-Metastatic Castration-Resistant Prostate Cancer (NCT01946204), a randomized phase 3 study. The primary outcome is Metastasis-Free Survival (MFS) by Blinded Independent Central Review (BICR).

2. Clinical Question

In statistical terms, the trial asks whether the time-to-event experience for the defined endpoint differed between randomized treatment groups. The endpoint combines distant metastasis and death, meaning that either event can determine the observed event time. This is a description of the trial question, not a conclusion about the treatment. The registry lists secondary outcomes including time to metastasis, progression-free survival, time to symptomatic progression, overall survival, and time to initiation of cytotoxic chemotherapy. Their presence identifies other outcomes of interest, but does not establish what their results were or how they compare between groups.

3. Trial Design

The registry describes a multicenter, randomized, double-blind, placebo-controlled phase III study with a parallel-group model. The study title identifies apalutamide, or ARN-509, as the study drug and men with non-metastatic castration-resistant prostate cancer as the target population. The brief description specifies adult men with high-risk disease. The comparator was placebo.

The record lists enrollment of 1207 and gives the study status as active, not recruiting. It records a start date of 2013-10-14 and a primary completion date of 2017-05-19. These registry fields describe the study record; they do not by themselves establish when every participant entered or left follow-up. The primary endpoint timeframe is listed as up to approximately 43 Months.

Randomization supports comparisons between assigned groups by reducing systematic differences in the allocation of measured and unmeasured participant characteristics, on average. That is a general property of randomized designs, not evidence that the groups were identical in this particular study. The parallel design means that the record describes treatment groups followed within the same trial rather than a crossover comparison. The registry records triple masking, but the identities of the masked parties are not reported in the registry record.

The primary analysis population is described as intent-to-treat: all randomized participants, analyzed according to initial assignment, whether or not they received the assigned study drug. This preserves the randomized comparison in the population specified by the record. The protocol, detailed eligibility criteria, treatment adherence information, and analysis plan are not reported in the registry record. The record names the sponsor as Aragon Pharmaceuticals, Inc.

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

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: Intent-to-Treat (ITT) population included all participants who were randomized into the study, with study drug assignments designated according to initial randomization, regardless of whether participants received what was assigned.

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 Metastasis-Free Survival (MFS) by Blinded Independent Central Review (BICR), measured over Up to approximately 43 Months.

Metastasis-free survival (MFS) is the primary endpoint. The registry defines it as the time from randomization to the first BICR-confirmed bone or soft tissue distant metastasis, or death due to any cause, whichever occurs first. BICR means blinded independent central review. The registry says radiographic scans, including bone scans and CT or MRI of the chest, abdomen, and pelvis, were performed for detection of metastasis throughout the study.

MFS is a time-to-event endpoint: it incorporates both whether an event occurred and when it occurred. Because metastasis or death can trigger the endpoint, it is a composite measure rather than a measure of metastasis alone. This can make the endpoint informative about time without either recorded event, while requiring careful interpretation of which event types contribute to it. That is a general feature of composite endpoints.

The registry specifies the median and a 95% confidence interval as the summary statistics, with the endpoint reported in months and a timeframe of up to approximately 43 Months. A median time-to-event estimate describes the time by which half of the relevant event-time distribution has reached the event, under the analysis method used. A confidence interval describes statistical uncertainty around an estimate; it is not a range containing a fixed proportion of individual participants’ event times. The actual group-specific medians and confidence intervals are not reported in the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

What does a time-to-event endpoint measure?

In general, a time-to-event analysis concerns both the occurrence and timing of a defined event. For this study, the registry defines the starting point as randomization and the event as the first BICR-confirmed bone or soft tissue distant metastasis or death from any cause, whichever happens first. The endpoint is therefore a composite. It does not treat metastasis and death as separate primary events in the definition, and the time recorded is determined by whichever qualifying event occurs first.

Time-to-event methods can use information from participants who have not had the event by the end of their observed follow-up, rather than treating them as if they had an event at that time. In general, these methods need rules for censoring and follow-up. The specific censoring rules and detailed handling of follow-up are not reported in the registry record. The record notes that MFS data for participants without metastasis or death were performed for US or ex-US regulatory purposes, but it does not describe those procedures in enough detail to infer an analysis method.

What does the median and confidence interval convey?

The registry specifies a median and 95% confidence interval for MFS. In general, a median is a measure of the event-time distribution, while a confidence interval conveys uncertainty around an estimated quantity. Wider intervals indicate less precision than narrower intervals, although the registry’s actual intervals are not reported. An interval should not be interpreted as a range that contains a fixed proportion of participant event times, nor does overlap or non-overlap alone supply a complete test of a group difference.

The record does not report the estimated medians or confidence intervals for either group. It also does not provide enough information to infer their uncertainty, compare their precision, or establish a numerical treatment contrast. A time-to-event endpoint can be summarized in more than one way; the record’s stated summary is the median with a 95% confidence interval. The particular calculation details are not reported in the registry record.

Why use blinded independent central review?

The endpoint is specified as assessed by blinded independent central review. In general, independent review can provide a standardized assessment of imaging outcomes and can reduce the influence of knowledge about assigned treatment on event classification. The registry says the study was triple-masked and that BICR was used for the MFS endpoint. It does not identify the roles covered by triple masking or describe the review charter, adjudication rules, or procedures for resolving disagreement. Those details should not be assumed.

What does the intent-to-treat population mean?

The registry defines the intent-to-treat population as all participants randomized into the study, with assignments based on initial randomization regardless of whether participants received what was assigned. In general, analyzing participants according to their randomized assignment retains the comparison created by randomization and reflects outcomes under assignment rather than only among those who adhered to treatment. The registry does not describe other analysis populations or deviations from the stated population.

The registry lists enrollment of 1207, but that entry should not be treated as a separately reported group allocation or as the count of participants with complete primary endpoint information. No group-specific randomized counts, losses to follow-up, or completeness figures are reported in the registry record.

How should hazard ratios and planning illustrations be read?

The record’s description of the time-to-event analysis says that only sponsor-reported hazard ratios are used. The actual hazard ratio results are not reported in the registry record. In general, a hazard ratio compares event rates between groups over follow-up under the model’s assumptions. It does not give the difference between median event times, and its interpretation depends on the event definition, analysis population, and model. No model details, proportional-hazards assessment, or sponsor estimate is available in this record.

The stated sample-size assumptions describe planning illustrations based on an observed effect, with a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. The effect to detect is described as a stated fraction of the observed effect. For time-to-event illustrations, the stated approach concerns the total number of events using Schoenfeld; other illustrations concern participants per arm. These are planning assumptions, not a report of the trial’s design justification. The sample-size illustrations are not observed power. The registry does not report the trial’s own sample-size justification, and no specific illustration values are reported in the registry record for interpretation.

Any recalculation from posted summary statistics would be an unadjusted calculation, not a substitute for the sponsor’s analysis. In general, recalculation cannot reproduce adjustments, censoring methods, stratification, or other analysis choices unless those details and the required data are available. The primary comparison is not reduced to one comparison in the registry description, so there is no single primary contrast to recalculate from the information recorded.

10. Multiplicity, Missing Data and Analysis Populations

The registry lists MFS as the primary outcome and names secondary outcomes of time to metastasis, progression-free survival, time to symptomatic progression, overall survival, and time to initiation of cytotoxic chemotherapy. It lists 6 outcome measures and 7 analyses. The record does not explain how those measures and analyses correspond, which comparisons were prespecified, or how many tests were used for each outcome.

When a study examines multiple outcomes, time points, or comparisons, the chance of at least one apparently unusual result can increase if each is tested separately. In general, multiplicity procedures can address that issue, but they may affect the interpretation of p-values and confidence intervals. The multiplicity adjustment, if any, is not reported in the registry record. The record’s note that the primary outcome has several categories or time points and was not reduced to one comparison further limits interpretation of a single primary contrast.

The registry specifies an intent-to-treat population comprising all randomized participants, analyzed by initial assignment regardless of whether they received the assigned intervention. It does not report the number of participants with endpoint data, the amount or pattern of missing observations, reasons for missingness, or methods used to handle missing data. It notes that MFS data for participants without metastasis or death were performed for US or ex-US regulatory purposes, but does not describe the analysis procedure. No assumptions about censoring, imputation, or sensitivity analyses can be made from that statement alone.

The analysis plan, interim analyses, and sample-size justification are not reported in the registry record. Their absence means that the record does not establish how multiplicity, missing endpoint information, or interim monitoring was handled.

11. 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 retention (3.8%), haematuria (2.0%), hydronephrosis (2.0%), urinary tract infection (1.2%), pneumonia (1.1%).

The adverse-event summary lists, for placebo, 398 participants at risk for serious adverse events and 92 affected; for apalutamide, it lists 803 at risk and 199 affected. For other adverse events, the record lists 398 at risk and 329 affected in the placebo group, and 803 at risk and 716 affected in the apalutamide group. The summary also records deaths of 1 for placebo and 10 for apalutamide. These are descriptive counts as recorded; the registry does not explain the relationship of the deaths to treatment or to an adverse event.

The most frequent serious adverse-event terms listed are Urinary Retention (3.8%), Haematuria (2.0%), Hydronephrosis (2.0%), Urinary Tract Infection (1.2%), Pneumonia (1.1%), and Acute Kidney Injury (1.0%). The registry does not give enough detail to establish the denominator or other context for interpreting each percentage beyond its listing among the top serious terms.

Counts and listed percentages are not, on their own, adjusted comparisons or evidence of causation. The registry does not report uncertainty intervals or a statistical comparison for these safety entries. They should be read as recorded safety summaries rather than as a complete assessment of comparative risk.

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

The registry record establishes that this was a randomized, placebo-controlled phase III study of apalutamide in men with non-metastatic castration-resistant prostate cancer. It defines an important time-to-event endpoint, MFS, and specifies an intent-to-treat population. It also reports selected adverse-event counts and terms. These details describe the study’s question and parts of its reporting, but they are not enough to determine the observed comparative MFS result.

The actual primary endpoint medians and 95% confidence intervals are not reported in the registry record. The record also does not include a primary hazard ratio or p-value. Therefore, no numerical statement about the size, direction, or precision of the primary comparison can be made from these registry entries. The endpoint definition is not itself a result, and the presence of a randomized design does not reveal the outcome.

Likewise, the listed secondary outcomes do not establish how those outcomes turned out. Their names show what was assessed, but estimates and uncertainty for them are not reported. Safety counts provide descriptive information, but do not by themselves establish comparative risks, causality, or a complete benefit-harm balance.

In general, an estimate should be interpreted together with its uncertainty, analysis population, endpoint definition, and analysis methods. A planning illustration is not observed power, and a recalculation from summary statistics would not replace the sponsor’s own analysis. The registry does not report sufficient primary results to apply those principles to a numerical treatment contrast. The appropriate conclusion is limited to what the record documents: the design and endpoint are specified, while the key comparative outcome estimates are not reported in the registry record.

13. Why This Trial Matters Statistically

This trial is statistically notable for its combination of randomization, masking, a placebo comparator, and a centrally reviewed time-to-event primary endpoint. Those design features define how the comparison was intended to be structured. The registry specifies an intent-to-treat population, which keeps the analysis tied to initial randomized assignment as described in the record.

The endpoint also illustrates why definitions matter. MFS includes distant metastasis and death as qualifying events. The resulting summary concerns time to either event, not time to metastasis alone. The use of blinded independent central review makes the method of endpoint assessment part of the statistical question: event classification is tied to central review rather than only to a local assessment. The registry does not provide further details of that review process.

The record also highlights the distinction between a trial’s design and its reported results. It documents the outcome chosen, the summary statistic, and the analysis population, but not the primary estimates needed to interpret the treatment contrast. Statistical readers should avoid treating a defined endpoint, enrollment entry, or list of analyses as evidence of a particular result.

Finally, the listed planning assumptions underscore that sample-size calculations are design illustrations, not a measure of what the trial observed. A planning exercise based on a stated fraction of an observed effect does not establish observed power. With the primary outcome estimates absent from the registry record, the most defensible statistical reading is methodological rather than comparative: the design and endpoint are identifiable, but the primary result cannot be quantified from this record.

14. 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 central limitation for interpreting efficacy is that the registry record does not report the group-specific MFS medians or their 95% confidence intervals. It also does not report the sponsor’s hazard ratio or a p-value for the primary outcome. The record states that the primary outcome has several categories or time points and was not reduced to one comparison. Without a reported contrast and its analysis details, the primary comparative effect cannot be reconstructed or interpreted as a single numerical result.

The record gives an endpoint definition and an intent-to-treat population, but does not report group-specific randomized counts, endpoint completeness, loss to follow-up, or detailed censoring rules. It does not describe missing-data handling or sensitivity analyses. Those omissions restrict assessment of how much follow-up information contributed to the endpoint estimates and how robust any estimate would be to analysis choices.

The registry lists secondary outcomes and analyses without mapping each analysis to a specific comparison or describing a multiplicity strategy. It does not report the statistical plan, interim analyses, or the trial’s sample-size justification. The planning assumptions described in the record are not a substitute for those details.

The safety summary presents counts and selected serious adverse-event terms, but no comparative estimates or uncertainty intervals. The listed deaths are not accompanied by information about cause or relationship to treatment. The registry’s triple-masking designation does not identify which roles were masked, and details of the BICR process are not reported. These limitations are specific to what the registry record documents and should not be filled by assumption.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: A Study of Apalutamide (ARN-509) in Men With Non-Metastatic Castration-Resistant Prostate Cancer — NCT01946204.
• Registry record last updated 2026-09-28; status last verified 2026-09.
• Results first posted 2018-06-19.
• 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.

18. Record Summary

The record describes a multicenter, randomized, double-blind, placebo-controlled phase III study of apalutamide in men with non-metastatic castration-resistant prostate cancer. It lists enrollment of 1207, a parallel design, triple masking, and an intent-to-treat primary population. The primary endpoint is MFS by blinded independent central review, defined from randomization to first confirmed distant metastasis or death from any cause.

The registry lists secondary outcomes and selected safety summaries. However, the primary MFS medians, confidence intervals, and sponsor-reported hazard ratio are not reported in the registry record. The record therefore describes the trial question and design but does not provide the estimates needed to characterize the primary comparative result.