Study Adding Multikinase Inhibitor Sorafenib to Existing Endocrine Therapy in Patients With Advanced Breast Cancer: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Study Adding Multikinase Inhibitor Sorafenib to Existing Endocrine Therapy in Patients With Advanced Breast Cancer (NCT00525161), a na phase 2 study. The primary outcome is Response Rate.

2. Clinical Question

The clinical question is about response during combination treatment, not about whether sorafenib is better than endocrine therapy alone. Because all participants were in a single group, the study cannot make a randomized comparison between adding sorafenib and not adding it. Observed changes in disease status would also need to be interpreted in the context of the existing endocrine therapy and the absence of a control group.

The primary endpoint timeframe is recorded as 12 weeks after treatment and 8 weeks after initial documentation of response. The description also says that disease response was assessed after 3 months by appropriate scans, with scans obtained every 2 months thereafter until progression. Patients were followed monthly for clinical and toxicity evaluation. The record does not explain how these time descriptions were reconciled for the primary analysis.

The registry names time to progression and clinical benefit rate as secondary outcomes. It does not report results for those outcomes in the information available for this analysis. The response question is therefore identifiable, but its answer cannot be established from the posted registry results.

3. Trial Design

This was a Phase II, single-group study of sorafenib added to existing endocrine therapy in patients with advanced breast cancer. The registry lists 11 participants enrolled and identifies Sorafenib & Endocrine Therapy as the study group. Allocation is listed as not applicable and masking as none. There was no separate control arm, so the study design does not support a like-for-like treatment comparison.

The study start is recorded as 2007-10, and primary completion as 2013-01. Its status is terminated. The registry record does not state why the study was terminated, and its status alone does not establish whether the planned enrollment or follow-up was completed.

The study purpose was to determine the clinical response rate to sorafenib when added to existing endocrine therapy. Response was assessed using RECIST v1.0 criteria for target lesions. The registry describes monthly clinical and toxicity evaluations, an assessment after 3 months by appropriate scans, and further scans every 2 months until progression. The recorded primary timeframe is 12 weeks after treatment and 8 weeks after initial documentation of response; the registry does not clarify how this relates to the assessment schedule.

The record says one participant discontinued treatment after 2 weeks owing to a grade 3 rash and was not evaluable for response. The analysis population and the handling of this participant in any outcome analysis are not reported in the registry record. The registry also does not describe the endocrine regimens, treatment duration beyond the discontinuation detail, or the reasons for termination. These omissions limit what can be inferred about how the study was conducted and how its outcomes should be interpreted.

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: one discontinued treatment after 2 weeks owing to a grade 3 rash and was not evaluable for response

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 Response Rate, measured over 12 weeks after treatment & 8 weeks after initial documentation of response.

The primary endpoint is Response Rate, measured in participants. The registry defines overall response as complete response plus partial response under RECIST v1.0 for target lesions. Complete response means disappearance of all target lesions. Partial response is defined as a decrease of at least 30% in the sum of the longest diameter of target lesions. The record says assessment was by MRI and describes scans after 3 months and then every 2 months until progression.

Response rate is used in clinical research to describe the proportion of participants meeting a prespecified definition of tumor response within an assessment framework. It reduces imaging findings to a clinically interpretable endpoint, while relying on the stated lesion criteria, assessment timing, and rules for determining which participants can be evaluated. These features matter because different assessment schedules or analysis populations can lead to different interpretations of a response summary.

The registry’s primary timeframe is recorded as 12 weeks after treatment and 8 weeks after initial documentation of response. It also notes monthly clinical and toxicity evaluation. The record does not explain the relationship between the timeframe wording and the described scan schedule.

Although the endpoint definition is available, the registry record does not report the number of complete responses, partial responses, or the overall response rate. The endpoint can therefore be described, but its observed result cannot be interpreted from the posted results.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

Statistical interpretation depends first on matching the method to the study question. This study’s primary question concerns response during sorafenib plus existing endocrine therapy. Since the registry records a single-group design and no comparator, a response summary would describe outcomes in that group. It would not, by itself, estimate the difference between combination treatment and endocrine therapy alone.

What does a response-rate estimate represent?

In general, a response-rate estimate is a summary of the participants who meet a defined response criterion among those included in the analysis. The definition matters: the registry uses RECIST v1.0, defines complete response as disappearance of all target lesions, and defines partial response as a decrease of at least 30% in the sum of the longest diameter of target lesions. Overall response is the combination of complete and partial responses. Applying these rules consistently is necessary for a meaningful estimate.

The registry record does not report the observed response count or response-rate estimate. It also does not report a confidence interval. In general, a confidence interval describes the statistical uncertainty around an estimate under specified assumptions. It does not resolve limitations of study design, missing assessments, or outcome measurement. Without the estimate and its uncertainty, readers cannot assess the precision of the response result from this record.

Why does the study design matter?

In general, random allocation to comparable groups can help balance factors that influence outcomes, making a between-group treatment contrast more interpretable. This study is recorded as single group, with allocation not applicable and masking none. There is no control-group result against which to compare the combination-treatment group. A single-group result can be informative as an observation, but it cannot isolate the contribution of sorafenib from the effects of existing endocrine therapy, participant characteristics, or other influences on response.

The study’s Phase II designation describes its phase, not the strength or certainty of any result. The record does not report a protocol-based sample-size justification, a statistical analysis plan, or details of any benchmark against which response might have been assessed. Those elements are not reported in the registry record and should not be inferred from the phase or enrollment.

How should the timing be read?

Outcome timing is part of the endpoint definition. The registry gives a primary timeframe of 12 weeks after treatment and 8 weeks after initial documentation of response. It also describes response assessment after 3 months, followed by scans every 2 months until progression. These descriptions are not fully reconciled in the record. In general, readers need to know which assessments contribute to the endpoint and how response is confirmed or classified over time. The record does not give additional rules on these points.

The registry says participants were followed monthly for clinical and toxicity evaluation. It does not state whether this schedule was maintained for every participant, how missed visits were handled, or how assessment timing varied. These details can affect the interpretation of outcome and safety summaries.

What do the planning assumptions mean?

The registry includes planning illustrations based on an observed effect, with a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. It says the effect to detect is a stated fraction of the observed effect. These are planning assumptions, not evidence that this trial randomized participants between two arms. They do not change the recorded single-group design.

In general, sample-size planning asks how much information a future study might need to detect a specified effect under chosen assumptions. Such calculations depend on the effect used, the statistical method, allocation, and the desired power. A planning illustration is not observed power and is not a measure of how likely the study was to find a real effect. The registry does not report the trial’s own sample-size justification, and the planning assumptions should not be mistaken for that justification.

Over-dispersion is a general concern when outcome variability exceeds what a model assumes; if ignored, uncertainty can be understated. The record identifies the primary outcome as binary and describes it in terms of participant counts, but it does not report an over-dispersion assessment or model-based adjustment. No such analysis should be presumed.

Finally, the registry reports 2 analyses but does not explain their methods or provide corresponding estimates in the record. No recalculated estimate is available in the registry record for this analysis. As a result, there is no basis to compare a sponsor analysis with a simple unadjusted recalculation or to comment on agreement between them.

10. Multiplicity, Missing Data and Analysis Populations

The registry lists response rate as the primary outcome and names time to progression and clinical benefit rate as secondary outcomes. It records 3 outcome measures and 2 analyses, but does not provide the analysis details or results needed to determine how these outcomes and analyses were handled together. A multiplicity plan is not reported in the registry record.

In general, testing several outcomes or conducting several analyses can increase the chance of finding an apparently notable result by chance. Statistical plans may address this through prespecified outcome hierarchies, adjustment procedures, or cautious interpretation. None of those approaches can be attributed to this study from the available record. The absence of a reported plan also means the relationship between the primary and secondary outcomes cannot be evaluated.

The record notes that one participant discontinued treatment after 2 weeks owing to a grade 3 rash and was not evaluable for response. It does not describe the full response analysis population, the handling of other incomplete assessments, or any imputation method. Missing-data handling is therefore not reported in the registry record.

In general, excluding participants without an evaluable outcome can affect an estimate if their outcomes differ from those of participants with complete assessments. The direction and size of any such effect cannot be determined from the single participant description. The record also does not state whether analyses followed an intention-to-treat principle or another defined population. No analysis population should be assumed beyond the explicit statement that this participant was not evaluable for response.

11. Safety Results

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

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: infection/herpes zoster (9.1%), colitis (9.1%).

The registry lists 11 participants at risk for serious adverse events and 2 participants with a serious adverse event. It also lists 11 participants at risk for other adverse events and 11 participants with an other adverse event. These are recorded participant counts, not evidence about whether an event was caused by treatment. The record does not provide a comparison group for interpreting safety differences.

The top serious adverse-event terms are Infection/Herpes Zoster at 9.1% and Colitis at 9.1%. These are the listed terms and percentages; the registry entries given do not describe event severity, timing, recurrence, or attribution for each term. The percentages should not be treated as a complete account of all safety observations.

One participant discontinued treatment after 2 weeks owing to a grade 3 rash and was not evaluable for response. This is a specific treatment-discontinuation detail. The record does not explain whether the rash is included in the serious-event count, and it should not be classified as serious based solely on the grade description.

In general, adverse-event counts summarize what was recorded under the study’s reporting rules. Small single-group safety summaries can identify events observed during study participation, but they cannot establish comparative risk or causation. The registry record does not report additional information needed for those conclusions.

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

The record supports a description of a Phase II, single-group study evaluating sorafenib added to existing endocrine therapy in advanced breast cancer. It identifies response rate as the primary endpoint, defines response using RECIST v1.0, and records enrollment of 11 participants. It also gives selected safety counts and notes one treatment discontinuation associated with a grade 3 rash.

The record does not report the primary response count or response-rate estimate. It therefore cannot show how often participants met the response definition, nor how precisely that result was estimated. The named secondary outcomes, time to progression and clinical benefit rate, also lack reported results in the record. Describing the study objective is not the same as demonstrating an outcome.

Even if a response result were available, a single-group design would not establish how the outcome compared with endocrine therapy without sorafenib. There is no separate control group in the recorded design. The observed course during combination treatment could not be attributed to sorafenib alone from this design.

The safety figures describe events recorded among participants at risk, not a causal treatment effect. There is no comparative safety group, and the registry record does not provide detailed event-level information. The available counts therefore should not be read as a complete or comparative assessment of safety.

In general, clinical trial results are interpreted alongside the endpoint definition, the analysis population, uncertainty, and study design. The registry record does not report enough information about the response analysis, missing data, or statistical methods to assess those aspects fully. The study’s terminated status does not explain why it stopped and does not substitute for an outcome result.

The most defensible conclusion is limited: the registry documents the study question, design, response criteria, and selected safety observations, but it does not provide the primary efficacy result. No conclusion about the treatment’s effect can be drawn from the missing response result or from the design alone.

13. Why This Trial Matters Statistically

This study illustrates why a clearly stated endpoint and a reported endpoint result are both necessary. The registry defines response using RECIST v1.0 and describes a scan schedule, allowing readers to understand what the study intended to measure. However, without the response count or estimate, the clinical question remains unanswered in the posted results.

It also illustrates the distinction between describing outcomes in a treatment group and estimating a treatment effect. The single-group design can describe observations among participants receiving sorafenib with existing endocrine therapy. It cannot provide the controlled contrast needed to isolate the added effect of sorafenib. This distinction is central when interpreting studies without a concurrent comparator.

The record further highlights the importance of transparent analysis populations. One participant discontinued after 2 weeks owing to a grade 3 rash and was not evaluable for response, but the full analysis population and handling of incomplete data are not reported. Without those details, readers cannot reconstruct the response denominator or judge how incomplete assessment may have influenced the result.

Finally, the safety information demonstrates why counts need context. Serious and other adverse-event counts and selected terms are recorded, but there is no comparison group and limited detail on event attribution. Such data describe recorded observations; they do not establish comparative risk. The study’s terminated status also underscores the importance of reporting reasons for stopping and outcome results, neither of which can be inferred from status alone.

Statistically, the record is most useful as an example of how design, endpoint reporting, analysis-population definitions, and missing-data transparency shape the conclusions a reader can draw. The information identifies what the study asked, but does not report the primary result needed to answer that question.

14. Limitations

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

The central limitation is that the registry record does not report the primary response result. Although it describes RECIST v1.0 criteria and an assessment schedule, it provides no response count or response-rate estimate. It also does not report a confidence interval or other measure of uncertainty for that endpoint.

The single-group design has no concurrent comparator. As a result, the record cannot support a like-for-like estimate of the effect of adding sorafenib to existing endocrine therapy. Allocation is listed as not applicable and masking as none. The record does not describe which endocrine regimens participants received, limiting interpretation of the treatment context.

The response timeframe and assessment schedule are not fully aligned in the registry description. The primary timeframe is recorded as 12 weeks after treatment and 8 weeks after initial documentation of response, while the description also specifies assessment after 3 months and scans every 2 months thereafter until progression. The registry does not explain how these statements were applied in the analysis.

One participant was not evaluable for response after discontinuing treatment at 2 weeks owing to a grade 3 rash. The full analysis population, handling of incomplete assessments, and missing-data methods are not reported. The reason for termination is also not reported in the registry record. Without the response result, protocol details, and analysis plan, these limitations cannot be resolved through reanalysis.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Study Adding Multikinase Inhibitor Sorafenib to Existing Endocrine Therapy in Patients With Advanced Breast Cancer — NCT00525161.
• Registry record last updated 2015-01-26; status last verified 2015-01.
• Results first posted 2015-01-13.
• 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

NCT00525161 is a terminated Phase II, single-group study of sorafenib added to existing endocrine therapy for advanced breast cancer. The registry records 11 participants enrolled, no masking, and no separate comparator group. The study start is listed as 2007-10 and primary completion as 2013-01.

The primary endpoint is response rate under RECIST v1.0. The record describes complete and partial response criteria and gives an assessment schedule, but does not report the response result. Time to progression and clinical benefit rate are listed as secondary outcomes without results in the record.

Safety information includes 2 participants with a serious adverse event among 11 at risk and 11 with other adverse events among 11 at risk. Infection/Herpes Zoster and colitis are each listed at 9.1% among the top serious terms. One participant discontinued after 2 weeks owing to a grade 3 rash and was not evaluable for response. The registry does not report the reason for termination, the full analysis population, or the primary outcome estimate.