To Study Clinical Effectiveness and Safety of Olaparib Monotherapy in Metastatic Breast Cancer Patients.: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for To Study Clinical Effectiveness and Safety of Olaparib Monotherapy in Metastatic Breast Cancer Patients. (NCT03286842), a non-randomized phase 3 study. The primary outcome is Progression-free Survival (PFS) in Real-world Setting in Germline BRCA Mutated Participants.

2. Clinical Question

The study asks how progression-free survival is characterized among participants with HER2-ve metastatic breast cancer and germline BRCA1/2 mutations who receive olaparib monotherapy in a real-world setting. Its primary endpoint is the time from the first dose of olaparib to disease progression or death from any cause. Progression is based on investigator assessment and may include radiological, symptomatic, or clearly documented progression of non-measurable disease.

The registry record identifies this as a phase IIIb, open-label, multicentre study. Its stated assessment period runs at every visit until the earliest of disease progression, death or end of study, up to 3 years. The record lists enrollment as 256, but does not report the primary endpoint estimate or its confidence interval. It therefore describes the question and endpoint, but does not provide the result needed to answer that question from the posted results.

3. Trial Design

This is a phase IIIb, open-label, multicentre, single-group study of olaparib monotherapy. The registry lists the allocation as non-randomized and masking as none. Participants received olaparib; no concurrent control group is described. As a result, the design can describe outcomes among treated participants but cannot directly estimate a treatment contrast against another arm within this study.

The registry record lists an enrollment of 256. The Full Analysis Set is defined as all participants who received at least one dose of study treatment. The record says that the number analyzed in both rows sums to the overall number, but does not include the primary endpoint row counts or endpoint estimates in the posted results. The enrollment figure should not be treated as an endpoint-specific denominator or as proof that every enrolled participant contributed to every analysis.

The study’s listed dates are a start on 2018-01-17 and primary completion on 2021-10-08; its status is completed. The primary endpoint is progression-free survival in real-world setting in germline BRCA-mutated participants. The registry defines the endpoint from first dose to progression or death from any cause, with investigator-assessed progression that may be radiological, symptomatic, or clearly documented progression of non-measurable disease.

Secondary outcomes include overall survival and several time-to-event measures in germline BRCA-mutated participants, clinical response rate and duration of clinical response, and adverse and serious adverse events. Although the registry record lists these outcomes, their estimates and analysis details are not reported in the posted results. The design information alone does not establish how endpoint follow-up, censoring, or analysis decisions were handled.

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: Participants who met the inclusion and none of the exclusion criteria were enrolled to the study. All study assessments were performed as per the schedule of assessment. A total of 256 participants were enrolled in this study but, only 255 started treatment.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: The Full Analysis Set consisted of all participants who received at least one dose of study treatment. The number analyzed in both the rows sums up to the overall number.

5. Baseline Characteristics

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

Population: The Full Analysis Set consisted of all participants who received at least one dose of study treatment.

6. Primary Endpoint

The registry lists the primary outcome as Progression-free Survival (PFS) in Real-world Setting in Germline BRCA Mutated Participants, measured over At every visit until the earliest of disease progression, death or end of study (up to 3 years).

Progression-free survival (PFS) is the time from the first dose of olaparib to the date of disease progression or death from any cause. The primary endpoint is specified for participants with germline BRCA mutations. The registry describes assessment at every visit until the earliest of disease progression, death or end of study, up to 3 years.

In general, PFS is a time-to-event endpoint: it incorporates both whether an event occurred and how long it took to occur. Including death from any cause means that death is counted as an event even if progression has not been documented first. In this study, progression is based on investigator assessment. The definition allows radiological progression, symptomatic progression, or clear progression of non-measurable disease when progression can be documented.

The registry specifies the median and a 95% Confidence Interval as the summary measures. In general, a median time-to-event estimate describes the time by which the estimated event experience has reached its midpoint; a confidence interval conveys uncertainty around that estimate. The interval does not give a guarantee about an individual participant’s course.

The median PFS and its 95% Confidence Interval are not reported in the registry record. Nor are the endpoint-specific number analyzed, event count, censoring details, or the method used to estimate the median reported. Consequently, the endpoint definition is available, but the magnitude and precision of the primary result cannot be assessed from the posted results.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry identifies the primary outcome as a time-to-event measure summarized by a median and a 95% Confidence Interval. It does not report the primary estimate or an analysis method in the posted results. The following concepts explain how such an endpoint is generally interpreted; they should not be taken as claims about procedures used in this study unless the registry record explicitly states them.

What does a time-to-event endpoint represent?

In general, a time-to-event outcome records the time from a defined starting point until a specified event. Here, the stated starting point is the first olaparib dose, and the event is disease progression or death from any cause. Participants whose event has not been observed by the end of their available follow-up may have incomplete event-time information. Statistical analyses of time-to-event outcomes commonly account for such incomplete observation, but the registry record does not report the censoring rules or how incomplete follow-up was handled for this endpoint.

What does the median mean?

In general, a median time-to-event estimate is a point on the estimated event-time distribution at which half of the estimated population has experienced the event. It is a summary of the distribution, not a prediction of the time an individual participant will experience an event. Its interpretation depends on the definition of the event, the follow-up information, and the analysis method. The registry names the median as the primary summary but provides no value, so the observed timing cannot be described.

How should a confidence interval be read?

In general, a confidence interval communicates statistical uncertainty around an estimated quantity. A narrower interval indicates greater precision than a wider interval, while either interval must be interpreted in the context of the data and method used. A 95% Confidence Interval is listed for the primary median, but neither endpoint of that interval is reported in the registry record. Precision therefore cannot be judged, and no estimate should be inferred from the endpoint description alone.

What can a hazard ratio tell a reader?

In general, a hazard ratio compares event rates over time between groups under a specified model. It is a relative measure, not a direct statement of how long participants live without an event. A hazard ratio requires a comparison, and interpretation depends on assumptions such as how the relative event rate behaves over follow-up. The study is single-arm, and the registry record does not report a hazard ratio for the primary endpoint. No comparative hazard estimate can be inferred from this record.

Why does the study design matter?

In general, random allocation can help make groups comparable at the start of a trial, on average, for measured and unmeasured characteristics. This study is listed as non-randomized, with a single-group model and no masking. It has no concurrent comparator arm. Outcomes in the olaparib cohort therefore cannot be interpreted as a randomized estimate of the difference between olaparib and another treatment. Open-label status means treatment masking is absent, but the registry record does not describe whether this influenced assessment or analysis.

What do the planning illustrations mean?

In general, sample-size calculations are design-planning exercises, not observed results. The registry’s stated planning assumptions describe 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. The record says time-to-event calculations give the total number of events, while other calculations give participants per arm. Such illustrations do not establish that the completed study used those design choices, and they are not observed power. The registry does not report its own sample-size justification. Without the corresponding result values, no numerical planning implication can be drawn for this trial.

The meaning field indicates that the time-to-event category uses only sponsor-reported hazard ratios. No such estimate is reported in the posted results. More generally, recalculation from posted summary statistics cannot replace a sponsor’s own analysis when the record flags a discrepancy; no primary endpoint analysis or recalculated PFS estimate is reported. The safest statistical reading is consequently bounded: the endpoint and its intended summary are defined, but the outcome estimate, its uncertainty, and the supporting analysis details are absent.

10. Multiplicity, Missing Data and Analysis Populations

The registry lists several secondary outcomes in the germline BRCA-mutated cohort, including overall survival; time to first subsequent treatment or death; time to second subsequent treatment or death; time to study treatment discontinuation or death; time to second progression or death; clinical response rate; duration of clinical response; and adverse and serious adverse events. The registry record does not report a statistical plan for managing multiple outcomes or multiple analyses. It is therefore not possible to determine whether any adjustment, hierarchy, or other prespecified approach was used to address the chance of false-positive findings across outcomes.

The record lists nine outcome measures and zero analyses. The listed primary endpoint’s median and 95% Confidence Interval are not reported in the posted results, and the registry does not provide results for the listed secondary outcomes. It does not report an interim analysis plan or results of interim analyses. These details are not reported in the registry record and should not be inferred from the study’s phase or completion status.

The Full Analysis Set is defined as all participants who received at least one dose of study treatment. The record says that the number analyzed in both rows sums to the overall number, but does not give the primary endpoint’s analyzed count or explain missing outcome data. The registry record does not report the amount, pattern, or handling of missing PFS assessments, nor does it state whether sensitivity analyses were used. In general, incomplete follow-up can affect time-to-event estimates if the assumptions used to handle it do not fit the data; whether that issue arose cannot be assessed.

These gaps matter because a statistical result is interpreted in light of its analysis population, outcome completeness, and analysis choices. The endpoint definition is available, but the record does not provide enough analysis detail to evaluate those elements for the primary or secondary results.

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: general physical condition abnormal (33.3%), anaemia (2.8%), febrile neutropenia (0.8%), vomiting (0.8%), asthenia (0.8%).

The registry reports safety figures for an Olaparib gBRCAm Cohort and an Olaparib sBRCAm Cohort. For the gBRCAm cohort, 252 are listed as at risk for serious adverse events and 32 as affected; 252 are listed as at risk for other adverse events and 243 as affected. The registry also lists 140 deaths for this cohort. For the sBRCAm cohort, the corresponding figures are 3 at risk and 1 affected for serious adverse events, 3 at risk and 3 affected for other adverse events, and 2 deaths.

These are cohort counts, not comparisons between randomized treatment groups. The study has no control arm, so the figures do not estimate how event counts would differ under another treatment. The registry record does not report the safety follow-up period, event definitions in detail, or whether each participant could contribute to multiple event categories. Death counts should not be assumed to represent deaths caused by treatment; attribution is not reported.

The registry lists serious adverse event terms and percentages: General physical condition abnormal, 33.3%; Anaemia, 2.8%; Febrile neutropenia, 0.8%; Vomiting, 0.8%; Asthenia, 0.8%; and Abscess, 0.4%. The denominator and calculation basis for these term percentages are not reported in the registry record. They should not be treated as directly comparable with the affected-participant counts without that information.

In general, adverse event summaries describe events recorded during a defined study period; they do not by themselves establish causation. The registry figures support a description of reported counts and terms, but not an estimate of excess risk relative to a comparator.

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

The registry record establishes that this completed, open-label, single-arm phase IIIb study evaluated olaparib monotherapy in HER2-ve metastatic breast cancer associated with germline or somatic BRCA1/2 mutations. It specifies PFS in germline BRCA-mutated participants as the primary outcome, defines the event as progression or death from any cause, and names the median with a 95% Confidence Interval as the intended summary. It also records adverse event counts for the gBRCAm and sBRCAm cohorts.

What the posted results do not establish is the primary PFS estimate, the width of its confidence interval, or any treatment contrast. Those results are not reported in the registry record. The listed enrollment of 256 is not a substitute for an endpoint estimate, and the record’s completed status does not supply the missing result. The reported safety counts also cannot establish whether events were more frequent than they would have been without olaparib or under another treatment.

In general, a single-arm study can describe the outcomes observed among participants receiving the study treatment, when those outcomes and their analysis are reported. It cannot, by itself, separate treatment effects from the natural course of disease, differences in care, participant characteristics, or other influences over time. A randomized comparator can support a more direct treatment comparison; none is described in this study.

The study’s endpoint definition also matters. Investigator-assessed progression can be radiological, symptomatic, or clear documented progression of non-measurable disease. The registry record does not report central assessment, consistency procedures, or missing-data handling, so the robustness of endpoint ascertainment cannot be evaluated from the posted results.

The appropriate conclusion is limited: the record describes the study question, design, endpoint definitions, and selected safety counts, but does not report the primary efficacy estimate or a comparative effect. It therefore does not provide enough statistical information to quantify PFS or its precision, or to infer what outcomes would have been under an alternative treatment.

13. Why This Trial Matters Statistically

This study illustrates why a clearly named clinical endpoint and an interpretable result are both necessary. The registry defines PFS by a time origin, an event rule, and an assessment setting: time begins at the first olaparib dose, and progression or death from any cause ends the interval. It also specifies investigator assessment and allows radiological, symptomatic, or clearly documented progression of non-measurable disease. Those details help readers understand what the outcome is intended to represent.

The registry also illustrates a key distinction between describing outcomes and estimating a treatment effect. The study is non-randomized and single-arm, with no concurrent comparator. Even if a cohort’s PFS were reported, an outcome in that cohort alone would not provide a randomized comparison with another treatment. This distinction is important when interpreting time-to-event outcomes from studies without a control group.

Statistical precision is another essential part of interpretation. A median without an uncertainty measure can be difficult to evaluate; the registry names a 95% Confidence Interval but does not report it. In this case, neither the median nor the interval is reported, so the central result and its precision are both unavailable. The record’s zero analysis entries make clear that the posted information does not provide an endpoint analysis to interpret.

The safety figures show a different limitation: counts are informative descriptions, but they require context such as follow-up duration, event definitions, attribution, and a comparator to support broader claims about risk. The registry provides cohort counts and selected serious adverse event terms, while several of those interpretive details are not reported in the registry record.

Overall, the record demonstrates that trial registration can convey population, intervention, endpoint definitions, and design features, while still leaving the quantitative outcome and analysis details unavailable. Statistical interpretation depends on both what was planned and what was reported, and those are not interchangeable.

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 main limitation for interpreting this trial statistically is that the registry record does not report the primary PFS result. The median and 95% Confidence Interval are specified as the intended summary, but neither is present in the posted results. The event count, endpoint-specific analyzed population, follow-up distribution, and censoring information are also not reported. As a result, the primary outcome’s magnitude and precision cannot be assessed.

The single-arm, non-randomized design has no like-for-like control comparison. Any outcome reported for the olaparib cohort would describe that cohort and would not, on its own, identify what would have occurred under another treatment. The open-label design also has no masking. The registry does not report whether outcome assessments underwent independent review or how possible assessment differences were addressed.

The primary outcome is based on investigator assessment and includes multiple types of documented progression. This is part of the stated endpoint definition, but the registry does not report procedures for standardizing assessments, handling equivocal findings, or dealing with missed visits. Missing-data methods and sensitivity analyses are not reported either. Their absence from the record prevents assessment of how incomplete observations might affect the analysis.

The registry lists a Full Analysis Set defined by receipt of at least one dose, but does not report endpoint-specific participant counts or analysis populations in the posted results. It also does not report a statistical plan, multiplicity approach, or the sample-size justification used for the trial. The planning assumptions described in the record are illustrations, not evidence of the trial’s own design rationale or observed power.

For safety, the registry reports cohort counts and selected serious adverse event terms, but the safety follow-up period, attribution, and percentage denominators are not reported. These limitations restrict what can be concluded from the safety summaries as well as from the efficacy endpoint.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: To Study Clinical Effectiveness and Safety of Olaparib Monotherapy in Metastatic Breast Cancer Patients. — NCT03286842.
• Registry record last updated 2023-01-17; status last verified 2022-11.
• Results first posted 2023-01-17.
• 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.

18. Record Summary

The registry record describes a completed phase IIIb, open-label, multicentre study of olaparib monotherapy in HER2-ve metastatic breast cancer associated with germline or somatic BRCA1/2 mutations. It lists non-randomized allocation, a single-group model, no masking, and enrollment of 256. Olaparib is described as 150mg tablets administered orally twice daily continuously.

The primary endpoint is PFS in the germline BRCA-mutated cohort, defined from first dose to progression or death from any cause and summarized by a median with a 95% Confidence Interval. The median and interval are not reported in the registry record. The record lists secondary outcomes and cohort-level safety counts, but does not report a primary analysis or comparative treatment estimate.

The study’s listed start date is 2018-01-17, primary completion date is 2021-10-08, and status is completed. The available information describes the design and intended outcome, but does not provide the quantitative primary result or enough analysis detail to evaluate its precision.