A Study of Niraparib in Combination With Abiraterone Acetate and Prednisone Versus Abiraterone Acetate and Prednisone for the Treatment of Participants With Deleterious Germline or Somatic Homologous Recombination Repair (HRR) Gene-MutatedProstatic Neoplasms (mCSPC): Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for A Study of Niraparib in Combination With Abiraterone Acetate and Prednisone Versus Abiraterone Acetate and Prednisone for the Treatment of Participants With Deleterious Germline or Somatic Homologous Recombination Repair (HRR) Gene-MutatedProstatic Neoplasms (mCSPC) (NCT04497844), a randomized phase 3 study. The primary outcome is Breast Cancer Gene (BRCA) Subgroup: Radiographic Progression-free Survival (rPFS) Assessed by Investigator.

2. Clinical Question

The study is a Phase 3 randomized comparison with a parallel-group design and triple masking. The registered primary outcome is a time-to-event measure: time from randomization to radiographic progression or death from any cause, whichever occurs first. That question is narrower than whether the combination changes every aspect of the disease course or every clinical outcome. Secondary outcomes include symptomatic progression, overall survival, time to subsequent therapy, and adverse events; the registered objective and primary analysis center on radiographic progression-free survival in participants with BRCA alterations.

3. Trial Design

This is a Phase 3, randomized, placebo-controlled, double-blind study with triple masking and a parallel-group model. The registry lists enrollment of 696 and describes a comparison of niraparib plus abiraterone acetate and prednisone against placebo for niraparib plus abiraterone acetate, with active abiraterone acetate and prednisone in both groups. The registry record does not describe the allocation ratio or identify which specific parties were included in triple masking.

The treatment descriptions specify administration in each 28-day treatment cycle. In the investigational group, niraparib 200 mg and abiraterone acetate 1000 mg are combined in a fixed dose combination; placebo for abiraterone acetate is also listed, along with prednisone 5 mg once daily. In the comparator group, participants receive matching placebo for the niraparib and abiraterone acetate fixed dose combination, active abiraterone acetate 1000 mg, and prednisone 5 mg once daily. Thus, the randomized contrast adds niraparib while retaining the abiraterone acetate and prednisone backbone.

The registry lists a study start date of 2020-09-23, a primary completion date of 2025-01-07, and status as active, not recruiting. The primary analysis population is the BRCA full analysis set, defined as randomized participants with a BRCA gene alteration classified according to assigned treatment regardless of treatment actually received. The primary endpoint entries list 196 participants in the placebo group and 191 in the niraparib group for this subgroup. These subgroup counts are not the same as the overall enrollment figure. Further details about randomization procedures, the allocation ratio, and the trial’s original statistical design assumptions 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: The results presented are based on the primary completion date (07 January 2025). Remaining results will be reported within a year of study completion.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: BRCA full analysis set (FAS) included all randomized participants with BRCA gene alteration classified according to their assigned treatment arm, regardless of the actual treatment received.

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 Breast Cancer Gene (BRCA) Subgroup: Radiographic Progression-free Survival (rPFS) Assessed by Investigator, measured over From date of randomization (Day -3 to Day 1) up to approximately 49 months.

The primary endpoint is investigator-assessed radiographic progression-free survival in the BRCA subgroup. It measures the time from randomization to the first radiographic progression or death from any cause, whichever occurs first. The registry gives a timeframe from randomization, described as Day -3 to Day 1, up to approximately 49 months.

Radiographic progression can be identified through changes in soft-tissue lesions assessed by CT or MRI under RECIST 1.1, or through bone lesions assessed by bone scan under PCWG3 criteria. For bone progression, the registry describes confirmation by a subsequent scan at least 6 weeks later and gives additional rules for interpreting new lesions relative to the Week 8 scan. These rules aim to distinguish a progression event from an unconfirmed scan finding.

As a general statistical concept, a time-to-event endpoint uses both whether an event occurred and the time until it occurred. It can retain information from participants who have not experienced the event by the analysis cutoff, provided their follow-up is handled appropriately. The registry record does not report the detailed handling of censoring or missing assessments. Radiographic progression-free survival is used because the study’s stated primary question concerns the timing of radiographic progression or death, rather than only the proportion experiencing an event at a single fixed assessment time.

7. Results Posted in the Registry

• BRCA Subgroup: Placebo With Abiraterone Acetate Plus Prednisone vs BRCA Subgroup: Niraparib With Abiraterone Acetate Plus Prednisone: hazard ratio 0.52 (95% CI 0.37–0.72), reported p < 0.001 (as reported in the registry).

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.

BRCA Subgroup: Time to Symptomatic Progression

• Endpoint type: Time to event: compared as a hazard ratio.
• Test: Hazard ratio as reported by the sponsor (Log Rank); it was not recalculated.
• Result:
  • BRCA Subgroup: Placebo With Abiraterone Acetate Plus Prednisone vs BRCA Subgroup: Niraparib With Abiraterone Acetate Plus Prednisone: hazard ratio 0.44 (95% CI 0.29–0.68), reported p = =0.0001 (as reported in the registry).
• Interpretation:
  • The 95% confidence interval excludes no difference (a ratio of 1), so the hazard of the event is statistically lower for BRCA Subgroup: Placebo With Abiraterone Acetate Plus Prednisone vs BRCA Subgroup: Niraparib With Abiraterone Acetate Plus Prednisone than for the control. This is an unadjusted, secondary comparison, so it is suggestive rather than confirmatory.

HRR Effector Subgroup: Time to Symptomatic Progression

• Endpoint type: Time to event: compared as a hazard ratio.
• Test: Hazard ratio as reported by the sponsor (Log Rank); it was not recalculated.
• Result:
  • HRR Effector Subgroup: Placebo With Abiraterone Acetate Plus Prednisone vs HRR Effector Subgroup: Niraparib With Abiraterone Acetate Plus Prednisone: hazard ratio 0.49 (95% CI 0.33–0.74), reported p = =0.0004 (as reported in the registry).
• Interpretation:
  • The 95% confidence interval excludes no difference (a ratio of 1), so the hazard of the event is statistically lower for HRR Effector Subgroup: Placebo With Abiraterone Acetate Plus Prednisone vs HRR Effector Subgroup: Niraparib With Abiraterone Acetate Plus Prednisone than for the control. This is an unadjusted, secondary comparison, so it is suggestive rather than confirmatory.

All HRR: Time to Symptomatic Progression

• Endpoint type: Time to event: compared as a hazard ratio.
• Test: Hazard ratio as reported by the sponsor (Log Rank); it was not recalculated.
• Result:
  • Placebo With Abiraterone Acetate Plus Prednisone vs Niraparib With Abiraterone Acetate Plus Prednisone: hazard ratio 0.50 (95% CI 0.36–0.69), reported p < 0.001 (as reported in the registry).
• Interpretation:
  • The 95% confidence interval excludes no difference (a ratio of 1), so the hazard of the event is statistically lower for Placebo With Abiraterone Acetate Plus Prednisone vs Niraparib With Abiraterone Acetate Plus Prednisone than for the control. This is an unadjusted, secondary comparison, so it is suggestive rather than confirmatory.

The posted time-to-symptomatic-progression analyses follow a consistent broad direction across the BRCA subgroup, the HRR effector subgroup, and all HRR participants: each reported hazard ratio is below the no-difference reference, and each reported interval is on that same side. These outcomes are clinically related to the primary radiographic progression-free survival endpoint, but they measure symptomatic progression rather than radiographic progression or death. They therefore add context rather than duplicate the primary endpoint.

The secondary analyses have their own populations and endpoint definitions, and their estimates should be interpreted within those boundaries. The registry also lists overall survival, time to subsequent therapy, and treatment-emergent adverse events as secondary outcomes. Numerical results for those outcomes are not reported in the registry record. Listing an outcome does not establish that a result was available or that the outcome supported a particular conclusion.

Secondary findings generally carry less inferential weight when the statistical plan does not state how multiplicity was handled. Testing multiple outcomes or subgroups can increase the chance that at least one result appears notable by chance. The registry record does not report a multiplicity adjustment or hierarchy for the secondary outcomes. The secondary results are thus best treated as supportive or exploratory context rather than as independent confirmation of the primary finding. They do not establish effects on overall survival or subsequent therapy when those results are not reported.

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

• BRCA Subgroup: Time to Symptomatic Progression
• HRR Effector Subgroup: Time to Symptomatic Progression
• All HRR: Time to Symptomatic Progression
• Overall Survival (OS)
• Time to Subsequent Therapy
• Number of Participants With Treatment-emergent Serious Adverse Events
• Number of Participants With Treatment-emergent Adverse Events by Severity

9. Statistical Interpretation

10. Statistical Methods Explained

Time-to-event analyses are useful when the outcome is defined by the timing of an event, such as radiographic progression or death. Participants may have different lengths of observation, and some may not have an event recorded by the time follow-up ends. In general, a time-to-event method can use the time under observation without treating every participant’s follow-up as if it ended at the same moment. The registry identifies the primary endpoint as radiographic progression-free survival and reports a Log Rank comparison and a hazard ratio. The detailed rules for censoring and incomplete assessments are not reported in the registry record.

What does the hazard ratio represent?

As a general explanation, a hazard is the event rate at a particular point in follow-up among participants who have not yet experienced the event. A hazard ratio compares that rate between groups over time. A value at the no-difference reference would indicate equal hazards under the model’s comparison; a value below that reference indicates a lower estimated hazard for the group in the numerator relative to the group in the denominator. The registry reports the primary hazard ratio as 0.515 with a 95% confidence interval of 0.37 to 0.717. The comparison is listed with placebo first and niraparib second, while the reported result is classified as superiority. The exact coding direction of the reported contrast is not separately explained in the registry record, so interpretation should retain the treatment-group labels and the sponsor’s superiority classification.

What does the Log Rank test do?

As a general statistical method, the Log Rank test compares the event experience of groups across follow-up, using the timing of events rather than only a final event count. It is commonly used in time-to-event settings. Its interpretation depends on the study design, event definitions, follow-up, and analysis assumptions. The registry identifies Log Rank as the method for the primary analysis and the reported secondary time-to-symptomatic-progression analyses. It does not report detailed diagnostics or the assumptions checked for those analyses.

How should the median be read?

The median time-to-event is the point by which half of the analyzed population is estimated to have experienced the event, under the time-to-event analysis. It is not the average follow-up time and does not describe the experience of every participant. The registry reports the control median as 25.99 months, with a 95% confidence interval from 22.11 to 41.17 months. For the niraparib group, a median value is not reported in the registry record; the lower confidence limit is 41.2 months, while an upper limit is not reported. When a median or confidence limit is not reported, it should not be filled in by inference.

What does a confidence interval add?

As a general explanation, a confidence interval describes statistical uncertainty around an estimate under the method’s assumptions. It gives a range of values compatible with the observed data and analysis, rather than a guarantee that the true value lies in that particular interval. The primary hazard-ratio interval extends from 0.37 to 0.717. Its placement below the no-difference reference is consistent with the reported superiority classification, while its width shows that the point estimate should not be treated as exact. Confidence intervals do not address all sources of uncertainty, such as selection effects, measurement error, or incomplete outcome capture.

What can a p-value tell a reader?

As a general explanation, a p-value measures how incompatible the observed data are with a specified null model, assuming that model and the analysis conditions. It is not the probability that the null hypothesis is true, and it does not measure the probability that the finding arose by chance in an unrestricted sense. The primary p-value is reported as < 0.001. That result is evidence against the null hypothesis used in the analysis, but it should be read alongside the estimated hazard ratio, its confidence interval, the endpoint definition, and the trial’s analysis context.

The registry also gives planning illustrations based on fractions of the observed effect. These are not the original design calculations for the trial. The registry’s original statistical plan, sample-size justification, interim-analysis procedures, and multiplicity strategy are not reported in the registry record. Those omissions matter when interpreting how the primary comparison was selected and how any additional analyses should be viewed.

11. Confidence Intervals and Precision

The primary hazard ratio is 0.515, and its 95% confidence interval runs from 0.37 to 0.717. The estimate is not a precise fixed quantity: the interval expresses uncertainty around it under the analysis method. Because the interval is below the no-difference reference, the data are compatible with a treatment-group contrast favoring the niraparib combination under the usual treatment-relative-to-control coding. The interval does not show the full range of possible uncertainty from design, measurement, or missing outcomes.

The control group’s median radiographic progression-free survival is 25.99 months, with a 95% confidence interval from 22.11 to 41.17 months. For the niraparib group, the median value and upper confidence limit are not reported in the registry record; the lower confidence limit is 41.2 months. This pattern of incomplete median reporting can occur in time-to-event results when the available event information does not support reporting every median or interval endpoint. The registry does not provide enough detail to characterize the reason for each unreported value.

A confidence interval is not a range containing most individual participants’ outcomes. It describes uncertainty around a group-level estimate. Nor does overlap or non-overlap of separate median intervals substitute for the reported between-group analysis. The hazard ratio and its interval are the direct comparative result for the primary endpoint. The confidence interval and p-value provide complementary information: the interval communicates the range of effect estimates compatible with the analysis, while the p-value addresses the null hypothesis under the test. Neither alone establishes clinical importance.

12. Planning a Similar Trial: Sample Size

This is a planning illustration, not a re-evaluation of the original trial. It asks: if a new study wanted to detect a difference like the one observed, or a smaller one, how large would it need to be? It is deliberately not “observed power” of the finished trial, which is not a meaningful quantity.

The event-planning figures for time-to-event outcomes are total event counts, not participants per arm. Their rows vary the target effect as a fraction of the observed effect, and the columns describe the total events needed under the stated planning assumptions for 80% or 90% power. For the primary comparison, the planning illustration lists 72 total events for 80% power and 96 total events for 90% power when planning for 100% of the observed effect. The other rows show the corresponding illustrations for 75% and 50% of the observed effect; the displayed figures should be read as event targets, not as enrollment targets.

The stated assumptions are a two-sided significance level of 0.05, equal allocation between the two arms, a normal approximation, and an effect to detect equal to the stated fraction of the observed effect. For general outcome types other than time-to-event, the planning convention is participants per arm; for these time-to-event calculations, it is total events. The trial’s own original design assumptions and sample-size justification are not reported in the registry record.

Power is the probability, under a specified effect and planning model, of rejecting the null hypothesis using the stated test. The 80% and 90% columns therefore represent different planned probabilities of detecting the target effect if the assumptions hold. Smaller effects require more information to distinguish them from no effect, which is why the planning figures rise as the assumed fraction of the observed effect becomes smaller. These calculations are planning illustrations based on the observed effect, not observed power.

13. How the Sample Size Is Derived

Power is the probability that a study of a given size rejects the null hypothesis when a specific true effect exists. It depends on four things: the effect to detect, the variability of the outcome, the significance level (here a two-sided α of 0.05, so z_1−α/2 = 1.960) and the desired power (z_1−β = 0.842 for 80% and 1.282 for 90%).

Formula

d is the total number of events needed (Schoenfeld's formula) with 1:1 allocation and proportional hazards.

Worked calculation for this trial

1. Hazard ratio HR = 0.515, so ln(HR) = -0.6636.
2. d = 4 × (1.96 + 0.842)² / [ln(0.515)]² = 71.3, rounded up to 72 events in total for 80% power.

The smaller-effect rows in the table above repeat the same calculation with the effect multiplied by 0.75 and 0.5 (for ratios, applied to the logarithm of the ratio).

R code

alpha <- 0.05
z_a   <- qnorm(1 - alpha / 2)          # two-sided
hr <- 0.515                              # observed hazard ratio
events_needed <- function(power, frac = 1) ceiling(round(4 * (z_a + qnorm(power))^2 / log(hr^frac)^2, 6))   # Schoenfeld, 1:1 allocation
for (f in c(1, 0.75, 0.5))
  cat(sprintf("%3.0f%% of observed effect: events = %s (80%% power), %s (90%% power)\n", 100 * f,
              format(events_needed(0.80, f), big.mark = ","), format(events_needed(0.90, f), big.mark = ",")))

# Simulation: given d total events under proportional hazards, events in the treatment arm are Binomial(d, hr / (1 + hr)).
# The score (log-rank type) statistic is (D1 - d / 2) / sqrt(d / 4).
set.seed(4497844)
d    <- events_needed(0.80)
reps <- 20000
D1 <- rbinom(reps, d, hr / (1 + hr))
z  <- (D1 - d / 2) / sqrt(d / 4)
cat(sprintf("Simulated power with %s events: %.3f (%d replicates)\n", format(d, big.mark = ","), mean(abs(z) > z_a), reps))

Output from running the code

100% of observed effect: events = 72 (80% power), 96 (90% power)
 75% of observed effect: events = 127 (80% power), 170 (90% power)
 50% of observed effect: events = 286 (80% power), 382 (90% power)
Simulated power with 72 events: 0.775 (20000 replicates)

The simulation uses the fact that, with d events in total and proportional hazards, the number of events in the treatment arm is binomial. It is an approximation that conditions on the total number of events, and it should land close to the target power.

14. Analyses Reported by the Sponsor

The registry reports the sponsor’s primary Log Rank analysis as a hazard ratio of 0.515, with a 95% confidence interval of 0.370 to 0.717 and p < 0.001. The primary comparison is identified as a superiority analysis. The reported primary outcome information also gives the arm-level median and confidence-limit entries, including values not reported for the niraparib median and upper confidence limit.

A simple recalculation from posted summary statistics, where available, is unadjusted and is not a replacement for the sponsor’s analysis. The registry record does not flag a discrepancy between the reported result and a recalculation. If a discrepancy were present, the sponsor’s own analysis would take precedence. The reported analysis should remain the principal inferential result because it is the trial’s stated analysis, while a summary-statistic recalculation cannot reproduce unreported participant-level methods, censoring decisions, or model details.

The registry does not report the full statistical analysis plan or explain all implementation details for the Log Rank analysis. The hazard ratio and confidence interval should therefore be attributed to the sponsor-reported analysis, without implying that a separate calculation independently validates every design or analysis choice.

15. Multiplicity, Missing Data and Analysis Populations

Multiplicity arises when a study evaluates several outcomes, subgroups, or comparisons. As a general statistical concern, the more hypotheses examined, the greater the possibility of observing a small p-value even when no corresponding effect exists, unless the analysis plan accounts for the family of tests. The registry lists a primary endpoint and secondary outcomes that include symptomatic progression in several populations, overall survival, time to subsequent therapy, and adverse-event outcomes. It also reports analyses for the primary BRCA subgroup endpoint and selected symptomatic progression outcomes.

The registry record does not report whether the trial used a formal multiplicity adjustment, a prespecified testing hierarchy, or another strategy to control the interpretation of multiple comparisons. It also does not report interim analyses or the full statistical analysis plan. Consequently, the primary result can be described as the registered primary analysis, while the secondary p-values should not be assumed to have confirmatory error control. Their statistical significance alone does not show that multiplicity was addressed.

The primary population is defined as the BRCA full analysis set: randomized participants with a BRCA alteration, classified by assigned treatment regardless of actual treatment received. This definition supports an assignment-based comparison. The registry does not provide a detailed account of missing outcome assessments, censoring rules, deviations from assigned treatment, or sensitivity analyses for incomplete data. Those details affect how a time-to-event estimate is constructed and how robust it may be to incomplete follow-up.

The registry reports investigator assessment for the primary radiographic endpoint and gives imaging and confirmation rules, but does not report further information about adjudication or assessment blinding procedures beyond the trial’s triple-masked designation. It is therefore important not to assume unreported analysis safeguards. The reported results can be interpreted as registry-record findings while recognizing that multiplicity, missing-data handling, interim monitoring, and the complete analysis population details beyond the stated FAS definition are not reported in the registry record.

16. 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: anaemia (5.8%), pneumonia (3.5%), urinary tract infection (2.6%), hypokalaemia (2.3%), acute kidney injury (1.7%).

The registry reports treatment-emergent serious adverse events among 96 participants in the placebo with abiraterone acetate and prednisone group, with 348 participants listed as at risk; the corresponding figures for the niraparib combination group are 136 and 347. For other treatment-emergent adverse events, the reported affected-participant counts are 326 of 348 in the placebo group and 338 of 347 in the niraparib group. Death counts are also listed as 108 and 85, respectively, but the registry entries do not establish the causes or attribution of those deaths.

These are counts of participants with events, not measures of severity across all events or an adjusted comparison of risk. The registry lists anaemia at 5.8%, pneumonia at 3.5%, urinary tract infection at 2.6%, hypokalaemia at 2.3%, acute kidney injury at 1.7%, and sepsis at 1.4% among the top serious-event terms. The listed percentages should be read as reported; the registry entries do not provide the full event-level context, exposure-adjusted rates, or a causal assessment. Differences in counts alone do not establish that treatment caused an event or characterize the complete benefit-risk profile.

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

The primary analysis reports a statistically clear difference in investigator-assessed radiographic progression-free survival for the BRCA subgroup: the reported hazard ratio is 0.515, its 95% confidence interval is 0.37 to 0.717, and p < 0.001. The registry classifies the comparison as superiority. The result is evidence from this randomized comparison for the specified endpoint and analysis population, not a guarantee of the same outcome for every participant.

The hazard ratio describes a relative event hazard over follow-up, not the probability that a participant will experience progression or death and not the number of months an individual gains. The registry reports the control median as 25.99 months and does not report the median in the niraparib group. The result should not be converted into a claim about absolute benefit or an individual prognosis. The endpoint includes death from any cause as well as radiographic progression, and the imaging definitions determine which progression events count.

The findings are limited to the BRCA subgroup for the primary endpoint. They do not establish the same effect for every HRR gene subgroup, the full study population, overall survival, or time to subsequent therapy. The registry lists secondary analyses, but it does not report numerical results for all listed outcomes or a multiplicity strategy. In particular, a primary radiographic progression-free survival result is not evidence by itself of an overall-survival effect.

Statistical evidence and clinical importance are related but distinct. A small p-value does not quantify the size or value of a clinical effect, and the confidence interval still allows a range of hazard-ratio values. The registry record also leaves important details unreported, including the full statistical analysis plan and handling of missing data. These limits do not erase the reported result; they define the scope of what can responsibly be concluded from the record.

18. Why This Trial Matters Statistically

This trial illustrates how a randomized, placebo-controlled design can isolate the added contribution of a study drug when the treatment backbone is retained in both groups. Here, the randomized contrast adds niraparib to abiraterone acetate and prednisone, while the comparator uses placebo for the niraparib-containing fixed dose combination alongside the same listed active backbone. The primary question is framed around a time-to-event endpoint in a biomarker-defined BRCA subgroup.

Statistically, the distinction between the arm-level median and the hazard ratio matters. A median summarizes a point on each group’s event-time distribution, while a hazard ratio uses the comparative event experience over follow-up. The registry reports a control median and a comparative hazard ratio, but not the treatment median. Reading the reported hazard ratio with its confidence interval and p-value avoids treating one summary statistic as a complete account of the event-time distributions.

The trial also demonstrates why subgroup scope, endpoint definitions, and secondary analyses matter. A result in the BRCA subgroup is not automatically a result for every HRR alteration or every listed outcome. The additional symptomatic-progression analyses offer related context, but the registry record does not report the multiplicity plan needed to treat multiple secondary tests as confirmatory. Recognizing these distinctions helps readers separate the main comparative finding from supporting results and unreported outcomes.

19. Limitations

• The posted summary statistics are the only data these results rest on; patient-level data, full protocols and statistical analysis plans are not available.
• Recalculated results are simple, unadjusted calculations from posted summaries. They do not replace the sponsor's prespecified analysis.

The registry record does not report the full statistical analysis plan, the original sample-size justification, the allocation ratio, or the specific parties covered by triple masking. It also does not report whether interim analyses were conducted or how multiplicity across secondary endpoints and subgroup analyses was handled. These gaps limit assessment of the prespecification and error-control context for the results.

For the primary time-to-event outcome, the record provides a median and confidence interval for the control group but does not report a median or upper confidence limit for the niraparib group. It does not give detailed censoring rules, missing-assessment procedures, or sensitivity analyses. As a result, the record alone cannot show how incomplete follow-up or missing imaging was handled in the analysis.

The primary endpoint relies on investigator-assessed imaging, with specified criteria for soft tissue and bone progression. The record does not provide further information on independent adjudication or assessment procedures beyond the registered masking description. The primary result is specific to the BRCA full analysis set; conclusions should not be extended automatically to other populations or outcomes.

Numerical results for several listed secondary outcomes, including overall survival and time to subsequent therapy, are not reported in the registry record. The adverse-event counts are not accompanied by exposure-adjusted rates, detailed event durations, or an attribution analysis. These limitations constrain interpretation of the full outcome profile and do not support causal conclusions from event counts alone.

20. Related Tutorials

21. Related Statistical Calculators

22. Sources

• ClinicalTrials.gov: A Study of Niraparib in Combination With Abiraterone Acetate and Prednisone Versus Abiraterone Acetate and Prednisone for the Treatment of Participants With Deleterious Germline or Somatic Homologous Recombination Repair (HRR) Gene-MutatedProstatic Neoplasms (mCSPC) — NCT04497844.
• Registry record last updated 2026-11-04; status last verified 2026-11.
• Results first posted 2026-01-22.
• 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.

23. Record Summary

NCT04497844 is a Phase 3 randomized, placebo-controlled, double-blind, triple-masked parallel-group study of niraparib with abiraterone acetate and prednisone versus placebo with abiraterone acetate and prednisone in participants with HRR gene-mutated metastatic castration-sensitive prostate cancer. The registry lists enrollment of 696 and status as active, not recruiting.

The primary outcome is investigator-assessed radiographic progression-free survival in the BRCA subgroup. The registry reports a Log Rank hazard ratio of 0.515, 95% confidence interval 0.37 to 0.717, and p < 0.001, with the comparison classified as superiority. The control median is 25.99 months; the treatment median is not reported in the registry record.

Secondary symptomatic-progression analyses are reported for BRCA, HRR effector, and all HRR populations. Other listed outcomes include overall survival, time to subsequent therapy, and adverse events. The record does not report numerical results for all listed outcomes or key analysis details such as multiplicity handling and missing-data procedures.