Niraparib + Dostarlimab In BRCA Mutated Breast Cancer: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Niraparib + Dostarlimab In BRCA Mutated Breast Cancer (NCT04584255), a randomized phase 2 study. The primary outcome is Change in Tumor-infiltrating Lymphocytes (TILs).

2. Clinical Question

3. Trial Design

This is a phase II study of niraparib with dostarlimab as neoadjuvant treatment for patients with BRCA-mutated breast cancer. The registry title also names the combination, and the record includes deleterious PALB2 mutation among the listed conditions. Dana-Farber Cancer Institute is the sponsor. The trial is registered as randomized, open-label, and parallel-group, with enrollment listed as 66. Its status is active, not recruiting.

The triple-negative breast cancer portion is described through two treatment schedules. Participants are randomized 1:1 to Arm A or Arm B. Arm A starts niraparib daily and dostarlimab once every three weeks, both beginning in week 1, day 1. Arm B starts daily niraparib in week 1, day 1, but delays dostarlimab until week 4, day 1, after a 3-week niraparib-only lead-in. The registry does not report further details of the allocation sequence, concealment, or how the randomized comparison is analyzed.

Arm C is an exploratory cohort for estrogen receptor-positive, HER2-negative participants. Its schedule starts daily niraparib and dostarlimab once every three weeks in week 1, day 1. The registry record does not describe a randomized comparator for Arm C, so it should not be interpreted as a third randomized schedule without additional information.

The listed start date is 2021-01-21, and the listed primary completion date is 2025-07-01. These dates are registry entries, not evidence that follow-up or analysis is complete. The planned or recorded enrollment is 66; the record does not establish how many participants were ultimately treated or contributed data to each outcome. Details of treatment duration, follow-up beyond the primary time point, and sample-size justification 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.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: The analysis population for TILs at baseline is patients that received treatment and had an evaluable baseline TILs measurement. The analysis population for TILs at Cycle 2 Day 1 is patients that received treatment and had an evaluable TILs measurement at Cycle 2 Day 1. The analysis populations for statistical testing in each arm (separately) is patients that received treatment in that arm and had an evaluable TILs measurement at both baseline and cycle 2 day 1

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 Change in Tumor-infiltrating Lymphocytes (TILs), measured over baseline to 21 days (cycle 2 day 1).

The primary endpoint is change in tumor-infiltrating lymphocytes (TILs) from baseline to 21 days, corresponding to cycle 2 day 1. A pathologist estimates the TILs score according to the International Immuno-Oncology Biomarker Working Group on Breast Cancer guidelines. The score represents the percentage of the tumor’s stromal area occupied by mononuclear immune cells on a stained tissue slide, on a scale from 0-100.

TILs provide a tissue-based measure of immune cells within the tumor environment. As a general statistical and biological concept, a change over time can describe whether the measured characteristic shifts during the treatment period. The registry description states that higher scores generally correlate with improved survival outcomes and better responses to chemotherapy. That association is contextual information; it does not establish that a change in TILs predicts an outcome in this study or that a treatment caused such a change.

The endpoint is summarized by a median and inter-quartile range. The median describes the midpoint of the observed values, while the inter-quartile range describes the spread of the middle portion of those values. These summaries can be useful when a distribution is skewed or contains extreme observations. The record does not provide the actual baseline or follow-up scores, the change estimate, or an uncertainty interval. It therefore does not establish the direction, size, or precision of any observed TILs change.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry identifies the study as randomized, open-label, and parallel-group. These terms describe different parts of trial design. Randomization refers to assigning participants by chance to treatment groups; a parallel design means the groups receive their assigned schedules alongside one another rather than crossing over between treatments. Open-label means masking is listed as none. These design labels do not supply the details of how assignments were generated, concealed, or analyzed; those details are not reported in the registry record.

What the primary summary describes

The primary outcome is change in TILs score from baseline to cycle 2 day 1, with the follow-up time described as 21 days. The score is a percentage measure of stromal area occupied by mononuclear immune cells. The endpoint uses the median and inter-quartile range rather than a mean and standard deviation. As a general statistical explanation, the median is less influenced by unusually high or low observations than the mean. The inter-quartile range describes the spread of the middle half of values and does not, by itself, show the full distribution or the precision of an estimated treatment effect.

A summary of changes within groups would not automatically establish a difference between treatment schedules. To assess a comparative effect in the triple-negative cohort, an analysis would need to define the contrast between Arm A and Arm B and estimate its uncertainty. The registry information does not state the specific comparison model, whether the analysis uses change scores or adjusts for baseline TILs, or whether other covariates are included. The actual endpoint estimates and uncertainty measures are also not reported in the registry record.

Reading the treatment schedules

Arm A and Arm B both involve niraparib and dostarlimab, but their timing differs. Arm B includes a 3-week niraparib-only lead-in before dostarlimab begins. Thus the design distinguishes the schedules by when dostarlimab starts, rather than by whether the listed drugs are present in the overall regimen. The registry does not explain the scientific rationale for the lead-in or specify how schedule differences are represented in the statistical analysis. Arm C is described as exploratory and has its own ER-positive, HER2-negative population; the record does not describe a randomized comparator for it.

In general, an exploratory cohort can provide descriptive or hypothesis-generating evidence, but its presence does not necessarily establish a confirmatory comparison. The registry lists outcomes for ER-positive/HER2-negative breast cancer and several other secondary outcomes, but does not state which analyses are confirmatory, how results are adjusted for multiple testing, or how conclusions should be prioritized.

Uncertainty and precision

A confidence interval, in general, gives a range of values compatible with the data under the assumptions of the analysis. A narrow interval indicates greater precision than a wide interval, but interpretation also depends on the outcome scale and the comparison being estimated. No confidence interval for the primary outcome is reported in the registry record, so its precision cannot be assessed. A p-value, if reported, would address compatibility with a specified null hypothesis under an analysis model; it would not measure the size or clinical importance of an effect. No primary-outcome p-value is included in the registry record for this analysis.

The record includes a sample-size planning illustration based on an observed effect, with a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. Such calculations are planning illustrations, not observed power and not evidence that an effect was found. The described approach considers detecting a stated fraction of an observed effect. The underlying observed effect, the specific fractions, and the resulting participant counts are not reported in the registry record in the information available for this explanation. The trial’s own sample-size justification is also not reported in the registry record. The planning illustration should therefore not be mistaken for the original design rationale or for proof that the study could detect a particular effect.

Why distribution and missingness matter

As a general statistical concept, distributions that are skewed or contain outliers can make a median-based description more informative than a mean-based description. The median and inter-quartile range still leave important questions unanswered: how many observations contributed, whether the groups had similar baseline values, and how differences were estimated. The registry says that the baseline TILs analysis population consists of treated patients with an evaluable baseline measurement, and that the cycle 2 day 1 population consists of treated patients with an evaluable measurement at that time. The information does not describe how participants with a measurement at only one time point enter the change analysis.

Missing measurements can affect estimates if the participants with observed data differ from those without observed data. General approaches may include assumptions about the missingness process and methods to address it, but the method used is not reported in the registry record. The number missing, reasons for missingness, and sensitivity analyses are not reported either. Consequently, the published endpoint population and the robustness of any result cannot be evaluated from the registry entries.

10. Multiplicity, Missing Data and Analysis Populations

The registry lists six outcome measures and eight analyses. Secondary outcomes include pCR rate in ER-positive/HER2-negative breast cancer, association between change in TILs score and pCR, RCB-0/1 response, and treatment-related adverse events. The primary outcome itself is described as having several categories or time points and is not reduced to one comparison in the registry information summarized for this analysis. No single primary treatment contrast or numerical primary result is available.

When a study assesses several outcomes, time points, cohorts, or statistical comparisons, the chance of at least one apparently notable result can increase if each is tested separately. As a general statistical concept, multiplicity procedures can control or otherwise address that issue, while a prespecified hierarchy can identify which findings are primary and which are exploratory. Whether the study used a correction, hierarchy, or other multiplicity strategy is not reported in the registry record. The significance level and analysis plan for the trial itself are also not reported in the registry record.

The listed analysis populations are outcome-specific. For baseline TILs, the population comprises treated patients with an evaluable baseline measurement. For cycle 2 day 1 TILs, it comprises treated patients with an evaluable measurement at that time. These descriptions do not fully specify the population for a paired change analysis or explain whether participants are analyzed according to randomized assignment. The sample count for each population, handling of participants with incomplete measurements, and analysis of protocol deviations are not reported in the registry record.

Missing-data methods and sensitivity analyses are not reported in the registry record. Without those details, it is not possible to determine how incomplete measurements affected the results or how dependent the findings may be on assumptions about missingness. The planned primary completion date and enrollment entry do not supply this analysis information.

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: platelet count decreased (5.3%), neutrophil count decreased (4.5%).

The registry reports serious adverse events by treatment group, using the number at risk and the number affected. In Arm A, 22 participants were at risk and 1 was affected by a serious adverse event. In Arm B, 24 were at risk and 0 were affected. In Arm C, 19 were at risk and 1 was affected. Deaths are listed as 0 in each of the three groups. These counts describe the safety entries recorded in the registry; they do not establish that all possible events were captured or explain event timing, severity details, or attribution to treatment.

The registry also lists other adverse events affecting 21 of 22 participants in Arm A, 23 of 24 in Arm B, and 15 of 19 in Arm C. These are counts in a separate adverse-event category, not a comparison of treatment effects. The most frequently listed serious-event terms are platelet count decreased, 5.3%, and neutrophil count decreased, 4.5%. The information does not give further event-level context, including whether participants experienced more than one event or the timing and duration of events.

As a general statistical principle, safety counts should be interpreted alongside the number exposed, follow-up duration, event definitions, and completeness of reporting. The registry record does not provide enough information to assess those features or to make a comparative safety conclusion.

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

The registry record establishes that a phase II study was designed to evaluate neoadjuvant niraparib and dostarlimab in breast cancer associated with BRCA or PALB2 mutations. It describes two randomized schedules for the triple-negative cohort and an exploratory schedule for ER-positive, HER2-negative participants. It also defines change in TILs from baseline to cycle 2 day 1 as the primary outcome. Those details describe the question and design, not the answer.

The primary TILs results are not reported in the registry record. There are no numerical group summaries or estimates of a between-group difference in the information available for this analysis. Consequently, the data presented do not show whether TILs increased, decreased, or remained similar, nor how precisely any such change was measured. The registry description of general associations between TILs scores and outcomes in other contexts cannot stand in for results from this trial.

The design also does not, by itself, establish that either schedule improves a clinical outcome. TILs is a biological measurement, whereas pCR, residual cancer burden, survival, and adverse events are distinct outcomes. The registry names some of these as secondary outcomes, but their results are not reported in the registry record. No claim about efficacy or comparative effectiveness can be made from the study description alone.

The safety entries are similarly limited. They report affected-participant counts and list deaths as 0 for each group, but the information does not provide all the details needed to characterize the full safety experience or compare risks. The counts should not be treated as definitive evidence of safety or of a difference between schedules.

Overall, the registered information permits a careful account of the population, intervention schedules, primary endpoint, and selected safety counts. It does not permit a conclusion about the treatment effect, the precision of the primary estimate, or whether the observed results support a clinical claim. Those questions require complete outcome results and the statistical methods used to analyze them.

13. Why This Trial Matters Statistically

This trial is statistically interesting because its randomized triple-negative cohort compares two schedules of the same named combination, with dostarlimab starting at different times. That makes the timing of treatment an important part of the question. A clear analysis would need to identify the precise contrast between the schedules and distinguish it from results in the exploratory ER-positive, HER2-negative cohort. The registry describes the design but does not report that full analysis framework.

The primary outcome is a tissue-based measure collected from baseline to cycle 2 day 1. It is not interchangeable with a clinical response endpoint. Studying a biomarker can provide information about a biological change during treatment, but interpretation depends on the measurement’s reliability, missingness, and relationship to outcomes in the study population. Although the registry description gives general context about TILs, it does not establish what the observed changes mean for participants in this trial.

The record also illustrates why design features and results must be kept separate. Randomization is a strength of a comparative design in general, while open-label treatment and an exploratory cohort shape the questions that can be answered. Neither the enrollment entry of 66 nor the existence of a sample-size planning illustration demonstrates that a particular effect was observed or estimated precisely. The original sample-size justification and primary statistical plan are not reported in the registry record.

Finally, multiple outcomes and populations make prioritization important. Without the prespecified hierarchy, multiplicity approach, analysis populations, and missing-data methods, readers cannot fully judge how confirmatory or exploratory findings should be interpreted. These omissions do not negate the registered design; they define the limits of what can be concluded from the registry information.

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 primary limitation is that the registry information available for this analysis does not include numerical results for the primary endpoint. It therefore cannot support an estimate of TILs change, a comparison of randomized schedules, or an assessment of precision. The listed secondary outcomes likewise have no reported results in the information.

The analysis populations are described separately for baseline and cycle 2 day 1 measurements, but the record does not explain the population used to calculate change, the number of participants with paired measurements, or how missing values were handled. Reasons for missing measurements and sensitivity analyses are not reported in the registry record. These omissions limit assessment of whether the available measurements represent all randomized participants.

The registry identifies the study as randomized and open-label, but the randomization procedure, allocation concealment, outcome-assessor masking, and statistical analysis plan are not reported in the registry record. The protocol’s sample-size justification is also not reported. A planning illustration based on an observed effect is not the same as the trial’s own design justification and cannot establish observed power.

The description distinguishes randomized Arm A and Arm B schedules in triple-negative breast cancer from the exploratory Arm C cohort. It does not provide enough detail to infer that Arm C is part of the randomized comparison. The primary endpoint’s multiple categories or time points are not reduced to one comparison, and multiplicity methods are not reported in the registry record.

Finally, the safety information is presented as affected-participant counts and selected event terms without additional detail about duration of exposure, event timing, severity, or attribution. The listed status and completion date do not establish that all results are available. These constraints mean that interpretation should remain descriptive and limited to the information recorded.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Niraparib + Dostarlimab In BRCA Mutated Breast Cancer — NCT04584255.
• Registry record last updated 2026-09-24; status last verified 2026-06.
• Results first posted 2026-09-24.
• 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

NCT04584255 is a phase II, randomized, open-label, parallel-group study sponsored by Dana-Farber Cancer Institute. It evaluates niraparib with dostarlimab as neoadjuvant treatment. The registry lists enrollment as 66 and status as active, not recruiting. The listed study start date is 2021-01-21, and the listed primary completion date is 2025-07-01.

For triple-negative breast cancer, the record describes randomization 1:1 between a schedule starting both drugs in week 1, day 1, and a schedule with a 3-week niraparib-only lead-in before dostarlimab starts in week 4, day 1. An exploratory ER-positive, HER2-negative cohort receives both drugs beginning in week 1, day 1.

The primary outcome is change in TILs score from baseline to 21 days, or cycle 2 day 1, summarized by median and inter-quartile range. The primary results, detailed statistical plan, multiplicity approach, and missing-data methods are not reported in the registry record. Serious adverse events affected 1 participant in Arm A, 0 in Arm B, and 1 in Arm C; deaths are listed as 0 in each group.