Treatment of Metastatic Castration-Resistant Prostate Cancer With Homologous Recombination Deficiency: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Treatment of Metastatic Castration-Resistant Prostate Cancer With Homologous Recombination Deficiency (NCT03712930), a na phase 2 study. The primary outcome is Objective Response Rate (ORR) Determined by Independent Review Committee.

2. Clinical Question

The study’s stated purpose was to evaluate pamiparib’s efficacy for participants with mCRPC and CTC-HRD, including objective response and PSA response. The primary endpoint addresses tumor response as assessed by an independent review committee. The record identifies additional outcomes involving response duration, investigator-assessed response, clinical benefit, PSA response and progression, and symptomatic skeletal events. However, a numerical result for the primary endpoint is not reported in the registry record. Without that result, the response percentage and its precision cannot be described from the registry information.

3. Trial Design

This was a phase 2, open-label, single-arm study of pamiparib for metastatic castration-resistant prostate cancer with homologous recombination deficiency. The registry record lists 13 participants enrolled and identifies BeiGene as the sponsor. The study started on 2019-02-05, had a primary completion date of 2020-08-06, and is listed as terminated.

All participants were to receive pamiparib, for a period up to 1 year. Because there was no comparator arm and masking was absent, the study design does not support a randomized, blinded comparison between treatments. The registry record does not report a control group or a treatment allocation process beyond identifying the study as single-group.

The primary outcome was objective response rate (ORR) determined by an Independent Review Committee (IRC), with a timeframe of up to 1 year and 6 months. The record defines a response as a best objective response of complete response or partial response confirmed at a subsequent timepoint at least 4 weeks later. The efficacy-evaluable population is described in relation to the Safety Analysis Set, baseline measurable disease, and post-baseline tumor assessment, with an exception concerning early discontinuation for progression or death before tumor assessment.

The registry lists secondary outcomes covering investigator-assessed response and clinical benefit, duration and timing of response, PSA response and progression, and time to symptomatic skeletal event. It lists 13 outcome measures, but no statistical analyses. A numerical primary endpoint result and details of the analysis actually performed are not reported in the registry record.

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: All subjects enrolled had unknown BRCA1/2 status at study entry and were assigned to cohorts 1B or 2B; there were no subjects known to be BRCA1/2 positive at enrollment.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: Efficacy-Evaluable Analysis Set: includes all participants in the Safety Analysis Set who had measurable disease at baseline and at least 1 post-baseline tumor assessment, unless they permanently discontinue pamiparib or the study early due to clinical progression or death before tumor assessment. Participants with available data were included in the analysis.

5. Baseline Characteristics

The table reproduces the baseline characteristics posted in the registry, which describe the participants analysed at baseline and help show whether the randomized groups were comparable.

6. Primary Endpoint

The registry lists the primary outcome as Objective Response Rate (ORR) Determined by Independent Review Committee, measured over Up to 1 year and 6 months.

Objective response rate is the percentage of participants whose best objective tumor response was complete response or partial response and was confirmed by an Independent Review Committee at a subsequent timepoint at least 4 weeks later. This endpoint counts confirmed responders in relation to the defined efficacy-evaluable population; it is not a measure of how long a response lasts. The registry lists the assessment timeframe as up to 1 year and 6 months.

Response rate is a binary-outcome summary: each eligible participant contributes as a responder or not a responder under the endpoint definition. It can therefore describe the frequency of a defined tumor response in the analyzed population. Independent review is part of the endpoint definition and distinguishes this primary assessment from the separately listed investigator-assessed response outcomes.

As a general statistical point, a response percentage is more informative when interpreted alongside its uncertainty and a clear account of the population included in its denominator. The registry record describes the efficacy-evaluable population but does not report the number included in that population, the number who responded, the ORR estimate, or an uncertainty interval. The endpoint is specified, but its observed value and precision are not reported in the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The methods described in the registry record are limited. It identifies the study as phase 2, open-label, and single-group; names IRC-determined ORR as the primary outcome; defines response and the efficacy-evaluable population; and lists secondary outcomes. It does not report the statistical analysis for the primary endpoint, an analysis population count, a numerical result, or an uncertainty interval. The explanations below describe general statistical concepts, not methods confirmed as having been used in this study.

What does a response percentage represent?

For a binary endpoint such as ORR, each participant is classified according to whether the prespecified response definition was met. A response percentage expresses the number classified as responders relative to the analyzed population. It describes the observed frequency in that population, rather than the time until an event or the duration of a response. The registry defines the response as complete response or partial response confirmed at a later assessment at least 4 weeks afterward.

The denominator is consequential. The registry’s efficacy-evaluable definition refers to participants in the Safety Analysis Set with measurable disease at baseline and at least 1 post-baseline tumor assessment, except for the stated early-discontinuation circumstance involving clinical progression or death before tumor assessment. The record does not report the number who satisfied that definition or explain how all missing assessments were handled. Without the denominator and responder count, the response percentage cannot be recovered from the registry information.

What would uncertainty add?

As a general explanation, a confidence interval gives a range of values compatible with the observed data under a stated statistical procedure. For a response percentage, it conveys the precision of the estimate; it does not remove limitations in the design or guarantee that the true value lies within the interval. The registry record does not report a confidence interval or identify the method used to calculate one. No interval should therefore be inferred from the endpoint description or the enrollment figure.

In a single-arm study, an interval around a response percentage would describe uncertainty about the response frequency in the study population under its analysis assumptions. It would not create a treatment comparison. In particular, a single-group estimate cannot provide the same direct comparative evidence as an estimate based on randomized groups.

What is the role of the IRC?

The primary endpoint specifies independent committee review for response confirmation. This identifies the assessment source used for the primary outcome and distinguishes it from investigator-assessed secondary outcomes. The registry record does not describe the review procedures, adjudication process, or any statistical handling of disagreement. Those details are not reported in the registry record.

How should planning illustrations be understood?

The sample-size assumptions describe a planning illustration based on the observed effect, not the trial’s own design. The stated illustration assumptions are a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation; the effect to detect is a stated fraction of the observed effect. Those are planning conventions, not evidence that this single-arm study included two arms or used those assumptions in its conduct. The record does not report the trial’s sample-size justification or its own planned statistical design. Any sample-size illustration is prospective and hypothetical: it is not observed power, does not change the available trial data, and cannot replace a reported endpoint analysis.

More generally, power is a design quantity related to the chance that a planned analysis will detect an effect of a specified size under stated assumptions. It is not a measure of whether a completed study’s result is reliable, and an observed estimate does not establish its own power. The registry does not report a trial-specific power calculation or the assumptions behind one.

What cannot be reconstructed?

The registry lists 0 analyses and does not report an ORR estimate, responder count, confidence interval, hypothesis test, or analysis procedure. It also does not report the actual analysis population size or the approach to missing outcome assessments. These omissions prevent an independent reconstruction of the primary endpoint analysis from the registry record. General statistical explanations can clarify how such analyses are commonly interpreted, but they cannot establish which procedure this study used.

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("Pamiparib")
n      <- c(12)
events <- c(0)
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  Pamiparib  12  0  0.0  0.0  26.5  0.0  24.2  0.2  24.7

11. Multiplicity, Missing Data and Analysis Populations

The registry lists 13 outcome measures, including the primary IRC-determined ORR and secondary outcomes involving response, clinical benefit, PSA measures, and symptomatic skeletal events. It lists 0 analyses. A multiplicity strategy describing how statistical testing across outcomes was handled is not reported in the registry record. Thus, the record does not establish whether results across multiple endpoints were adjusted, prioritized, or treated as descriptive.

Missing-data handling is also not reported in the registry record. The primary endpoint description defines an efficacy-evaluable population using measurable baseline disease and at least 1 post-baseline assessment, with a stated exception for early discontinuation due to clinical progression or death before tumor assessment. That definition identifies which participants are intended to contribute under the described eligibility rule, but it does not provide the resulting population size or a complete account of how unobserved assessments were classified. No imputation method or sensitivity analysis is reported.

The registry does not report the number included in the Safety Analysis Set or the efficacy-evaluable analysis population. Therefore, the enrollment figure should not be substituted for an endpoint denominator. The record also does not describe whether any participants were excluded from a particular outcome analysis or how follow-up ending before assessment affected secondary outcomes.

These limitations affect interpretation of both the response estimate and its precision. Without an analysis population, missing-data rules, and a multiplicity approach, the registry information is insufficient to assess how those choices shaped the reported evidence. The primary result itself is not reported in the registry record.

12. Safety Results

The registry reports serious adverse events as affected participants divided by participants at risk.

Deaths

Other (non-serious) adverse events

Participants with at least one non-serious event at or above the registry's 0% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: pyrexia (15.4%), anemia (7.7%), back pain (7.7%), dehydration (7.7%), febrile neutropenia (7.7%).

The registry lists 13 participants at risk for serious adverse events and 6 affected. It lists 13 participants at risk for other adverse events and 13 affected. These are separate registry summaries; they should not be combined or treated as mutually exclusive groups. The record also lists 9 deaths. It does not report whether the deaths were attributed to pamiparib, the underlying disease, or another cause.

The serious adverse event terms highlighted in the record are pyrexia (15.4%), anemia (7.7%), back pain (7.7%), dehydration (7.7%), febrile neutropenia (7.7%), and hemiparesis (7.7%). These percentages describe the registry’s listed terms; they do not establish causation. The record does not provide further context about event timing, severity beyond the serious-event classification, duration, management, or relationship to study treatment.

Adverse-event counts and percentages are descriptive safety information. They do not, on their own, establish comparative risk because the study has no comparator group. The registry record does not report additional details needed to interpret the listed events in relation to treatment exposure or clinical course.

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

The registry record establishes the question this study was designed to address: whether participants with mCRPC and HRD, including the CTC-HRD population described in the study summary, had confirmed objective responses while receiving pamiparib. It specifies the primary endpoint, the IRC assessment, the response definition, and the intended timeframe. It also lists secondary outcomes and descriptive safety counts.

However, the record does not report the primary ORR result, the response count, a confidence interval, or a statistical test. It therefore does not show the size or precision of the observed response percentage. The description of an endpoint is not itself evidence that the endpoint was met. The study’s stated purpose to evaluate objective and PSA response should likewise not be read as a reported result.

The single-arm, open-label design also limits what a response estimate could establish. Without a comparator arm, the registry does not give a randomized comparison of outcomes. A numerical response percentage, if reported elsewhere, would need interpretation in light of the analysis population, missing assessments, outcome assessment procedures, and the absence of a concurrent control. The registry does not report enough statistical detail to resolve those issues.

The safety information records affected-participant counts, listed serious-event terms, and deaths, but it does not establish that events or deaths were caused by pamiparib. The study is listed as terminated, and the reason for termination is not reported in the registry record.

In short, the registry information describes a phase 2 study and its planned efficacy question, but it does not provide the numerical efficacy analysis needed to characterize the observed ORR. It should not be read as demonstrating that pamiparib does or does not produce a clinical benefit.

14. Why This Trial Matters Statistically

This study illustrates why a clearly defined endpoint and a reported endpoint result are both necessary for statistical interpretation. The registry defines ORR using confirmed complete or partial response assessed by an IRC, and it identifies the timeframe and the efficacy-evaluable population. Those details clarify what the primary measure was intended to represent. Yet the registry record does not report the response percentage, the number of responders, or an uncertainty interval. A well-specified question cannot substitute for the answer.

The design also makes the distinction between describing outcomes and comparing treatments especially important. This was an open-label, single-arm study with no comparator group. Any single-group outcome summary would describe the observed study population; it would not by itself provide a randomized treatment contrast. This distinction is central when communicating evidence from early-phase studies.

The record further demonstrates how analysis-population definitions shape interpretation. The primary endpoint uses an efficacy-evaluable population rather than simply naming all enrolled participants. The registry’s eligibility description includes measurable baseline disease and post-baseline assessment requirements, but the resulting analysis population and missing-data approach are not reported. Without those details, readers cannot assess the endpoint denominator or reproduce the analysis.

Finally, safety counts require careful separation from causal conclusions. The registry records serious adverse events, other adverse events, and deaths, but does not report attribution or a comparative safety analysis. The statistical value of these data depends on transparent definitions, denominators, follow-up, and context. The record supplies some descriptive elements, but not enough to make comparative or causal conclusions.

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 identifies the study as terminated but does not report why it was terminated. It lists 13 participants enrolled, but does not report the primary endpoint result or the size of the efficacy-evaluable population. The enrollment figure should not be treated as the denominator for ORR without a reported analysis population.

The study is single-arm and open-label, with no comparator group. This design means the registry record does not contain a randomized between-group comparison. The primary endpoint is IRC-assessed, but the record does not describe the IRC procedures, how response disagreements were resolved, or whether assessment details changed during the study.

The registry does not report a numerical ORR estimate, responder count, confidence interval, statistical test, or analysis method. Although 13 outcome measures are listed, the record lists 0 analyses and does not describe a multiplicity strategy. Missing-data methods, sensitivity analyses, and the handling of participants without evaluable post-baseline assessments are also not reported.

The endpoint population definition includes conditions on baseline measurability and post-baseline assessment, with a stated exception related to early discontinuation for progression or death. The record does not provide enough information to determine how many participants met the definition or how all potential assessment gaps were treated. This limits assessment of both the denominator and potential selection effects.

For safety, the registry lists participant counts, percentages for selected serious adverse event terms, and deaths, but does not report attribution, timing, exposure-adjusted summaries, or a control group. The reason for termination and the trial-specific sample-size justification are not reported in the registry record.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Treatment of Metastatic Castration-Resistant Prostate Cancer With Homologous Recombination Deficiency — NCT03712930.
• Registry record last updated 2021-11-17; status last verified 2021-10.
• Results first posted 2021-11-17.
• 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

NCT03712930 is a phase 2, open-label, single-arm study of pamiparib for metastatic castration-resistant prostate cancer with homologous recombination deficiency. The registry lists BeiGene as sponsor, 13 participants enrolled, a start date of 2019-02-05, a primary completion date of 2020-08-06, and a terminated status.

The primary endpoint is IRC-determined ORR, defined as confirmed complete or partial response in the stated efficacy-evaluable population. The registry lists additional response, PSA, clinical benefit, and symptomatic skeletal event outcomes. It does not report a numerical primary endpoint result or statistical analyses.

Safety listings include serious and other adverse event counts, selected serious-event terms, and deaths. Their attribution and comparative interpretation are not reported in the registry record.