A Study of Sunitinib in Combination With Bevacizumab and Paclitaxel in Previously Untreated Patients With Metastatic Breast Cancer (SABRE-B): Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for A Study of Sunitinib in Combination With Bevacizumab and Paclitaxel in Previously Untreated Patients With Metastatic Breast Cancer (SABRE-B) (NCT00434356), a randomized phase 2 study. The primary outcome is Best Response.

2. Clinical Question

The central clinical question is whether adding sunitinib to bevacizumab and paclitaxel was associated with a different pattern of best response in this trial population. The study was described as a preliminary assessment of safety and efficacy, not as a definitive estimate for all patients with metastatic breast cancer.

Best response was defined as the best RECIST response recorded from randomization until disease progression or recurrence, including confirmed and unconfirmed responses. The outcome was to be assessed by patient. The registry record says that progression-free survival was the original primary outcome, but that there was insufficient data available to report it; best response is the posted primary outcome instead.

The record also lists serious adverse events, grade 3 or higher adverse events, adverse events leading to death, and events leading to treatment discontinuation, interruption, or dose reduction among the secondary outcomes. The posted safety counts describe events in each treatment group, but do not resolve the primary efficacy question. Response counts, uncertainty estimates, and a treatment-effect analysis are not reported in the registry record.

3. Trial Design

SABRE-B was a multicenter, randomized, controlled, open-label Phase II trial with a parallel-group design. It enrolled 46 participants and is listed as terminated. The record gives a start date of 2007-03 and a primary completion date of 2008-05; the reason for termination is not reported in the registry record.

The treatment combinations identified in the posted adverse-event data are bevacizumab plus paclitaxel plus sunitinib, and bevacizumab plus paclitaxel. For the safety outcomes, 23 participants were at risk in each group. The detailed arm descriptions are blank in the registry record, so further treatment procedures, doses, or schedules are not reported there.

Randomization assigns participants to treatment groups by chance. In general, this can help make groups comparable at the start of a trial, although randomization does not guarantee balance in a small study. Open-label means the trial was not masked; who knew the assigned treatment and whether outcome assessment had any separate masking are not reported in the registry record. The parallel design means the groups received their assigned treatment strategies rather than switching between them, as a general description of this design.

The registry describes the study as intended to provide a preliminary assessment of safety and efficacy among patients who had not previously received chemotherapy for locally recurrent or metastatic breast cancer. It does not report the planned sample-size justification, allocation procedures in further detail, or the reason the trial ended. The recorded enrollment and completion information should not be taken as evidence that the trial completed its originally intended course.

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

Analysis population for the primary outcome, as defined in the registry: Randomized patients with at least one scan available at baseline and post-baseline

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 Best Response, measured over From randomization until disease progression/recurrence (by patient).

The posted primary outcome is best response, measured as the number of participants. It records each patient's best overall response, according to RECIST, during the period from randomization until disease progression or recurrence. The definition includes confirmed and unconfirmed responses. The outcome population includes randomized patients with at least one scan available at baseline and after baseline.

In general, a best-response endpoint reduces a sequence of tumor assessments to the most favorable response category recorded during a defined follow-up period. It can describe observed tumor response without requiring a time-to-event estimate. Its meaning depends on the response criteria, assessment schedule, availability of scans, and rules for handling missing or unevaluable assessments. The registry record does not report those operational details beyond the stated RECIST definition and scan requirement.

The record says progression-free survival was the original primary outcome, but there was insufficient data available to report that outcome. Best response is therefore the primary outcome shown in the record. These endpoints answer different statistical questions: a response summary describes the best recorded response, whereas progression-free survival concerns time until progression or death under its defined rules. The record does not provide progression-free survival results or enough detail to reconstruct them.

No participant counts by response category, effect estimate, confidence interval, or test result for best response are reported in the registry record. Accordingly, the endpoint definition can be described, but the size and precision of any difference between the groups cannot be assessed from the posted primary-outcome information.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The statistical information in the registry record is limited. It describes a randomized, controlled, open-label, parallel-group Phase II study and identifies best response as the primary outcome. It does not report an analysis plan, inferential results, or response counts. The concepts below explain how such information is generally interpreted; they do not imply that a particular method was used in this trial.

What randomization contributes

In general, random assignment is intended to reduce systematic differences between treatment groups at the start of a trial. It does not ensure that every measured or unmeasured characteristic is balanced, particularly in a small study. Randomization also does not prevent differences arising after assignment, such as incomplete outcome assessments. The registry record identifies the allocation as randomized but does not describe the method used to generate or conceal assignments.

The trial is open-label. In general, lack of masking can affect behavior, reporting, and assessment, depending on the outcome and the procedures used. RECIST response assessment uses defined criteria, but the registry record does not say whether image review was independent or blinded, or how response assessments were organized. It would be inappropriate to assume such procedures were or were not used.

How best response is interpreted

Best response selects the best overall response recorded for each participant during the stated follow-up period. This is a participant-level outcome, but it is based on assessments made over time. The record specifies that both confirmed and unconfirmed responses count. It also specifies that a participant must have a baseline scan and at least one post-baseline scan to be included in the primary-outcome population.

In general, a response outcome may be summarized by counts in its possible categories, or by a prespecified contrast that combines categories. The analysis depends on the category definitions and the contrast chosen. The registry record does not provide response category counts or describe a planned comparison. The number of categories and the exact response-analysis approach are therefore not reported in the registry record. The posted endpoint should not be reduced to a single treatment comparison without those details.

What uncertainty measures would add

In general, a confidence interval describes a range of effect values compatible with the observed data under the assumptions of the analysis. Its width conveys precision; it does not guarantee that the true effect lies within the interval, nor does it establish clinical importance. A p-value, when used, measures how surprising data at least as extreme as those observed would be under a specified null model. It does not measure the probability that a treatment effect is real.

No confidence interval or p-value for best response is reported in the registry record. Without an effect estimate and uncertainty measure, the primary outcome cannot be evaluated for either the direction or precision of a group difference. The fact that an outcome is designated primary does not itself provide evidence about the result.

How to read the safety counts

The safety record gives the number at risk and the number affected for serious adverse events in each treatment group. These are descriptive counts. In general, comparing counts alone does not account for uncertainty, differences in exposure time, or event severity and recurrence. The record does not state an exposure-adjusted analysis or provide inferential comparisons for safety. It also does not report death counts in the adverse-event data.

For multiple event terms, a participant may contribute to more than one term. Consequently, event-term counts or percentages should not automatically be added to obtain a total number of participants. The record lists several serious-event terms and percentages but does not provide the corresponding arm-specific participant counts for each term.

What sample-size planning means

In general, sample-size planning depends on an assumed effect, variability or event frequency, significance level, allocation, and desired power. The registry record does not report its own sample-size justification. Planning illustrations based on an observed effect are not observed power and do not show that a trial had a particular probability of finding a result after the data are known. They instead describe planning requirements under stated assumptions. The observed primary effect needed for such an illustration is not reported in the registry record, so no numerical planning result can be interpreted from this record.

The statistical interpretation is therefore constrained by missing outcome and analysis results. The design and endpoint are identifiable, but the record does not report the statistical methods used to compare best response, the precision of estimates, or the treatment-effect results.

10. Multiplicity, Missing Data and Analysis Populations

The registry record lists six outcome measures and names several safety outcomes, including serious adverse events, grade 3 or higher adverse events, adverse events leading to death, and events leading to treatment changes. It does not list analysis results. The multiplicity strategy, including whether any adjustment or hierarchy was planned for several outcomes or comparisons, is not reported in the registry record.

In general, testing multiple outcomes can increase the chance of obtaining at least one apparently notable result by chance. A prespecified hierarchy or multiplicity adjustment can address that issue, but the registry record does not say whether either was used. Since no p-values or outcome-specific analyses are listed, multiplicity cannot be evaluated from the posted results.

The primary-outcome population is defined as randomized patients with at least one scan at baseline and post-baseline. The record does not report how many participants met that requirement, how many lacked scans, or how missing or unevaluable assessments were handled. It also does not describe an imputation method, sensitivity analysis, or analysis population beyond the stated primary-outcome definition. The reason progression-free survival could not be reported is not given beyond the statement that data were insufficient.

In general, excluding participants without post-baseline assessments can affect interpretation if the excluded participants differ from those assessed. The direction and extent of any such effect cannot be determined without the relevant participant counts and missing-data information. The record also does not report whether the primary analysis followed all randomized participants or used another population beyond its stated scan-based criterion.

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: febrile neutropenia (8.7%), chest pain (8.7%), upper respiratory tract infection (8.7%), dehydration (8.7%), neutropenia (4.3%).

For serious adverse events, the posted safety counts are 10 participants affected among 23 at risk in the bevacizumab, paclitaxel, and sunitinib group, and 9 affected among 23 at risk in the bevacizumab and paclitaxel group. These are counts of participants, not a reported estimate of the difference between treatments. No confidence interval or statistical comparison for these counts is reported in the registry record.

The serious-event terms listed include febrile neutropenia, chest pain, upper respiratory tract infection, and dehydration, each reported as 8.7%, and neutropenia and hemolytic anemia, each reported as 4.3%. The registry record does not give an arm-specific breakdown for these terms. The percentages should therefore be read as the posted term-level values, not as evidence of a difference between treatment groups.

Adverse events leading to death are among the listed outcomes, but death counts are not reported in the posted safety data. The record also lists other adverse-event counts, but does not supply a statistical comparison. In general, adverse-event counts are descriptive and should be interpreted alongside definitions, follow-up, and exposure; those further details are not reported in the registry record.

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

The registry record supports a description of a randomized Phase II trial that enrolled 46 participants, its treatment groups, its stated primary endpoint, and selected safety counts. It does not report the best-response results, although best response is identified as the primary outcome. It also says that progression-free survival was the original primary outcome but that insufficient data were available to report it.

As a result, the posted information does not establish the direction or magnitude of an efficacy difference between the groups. It does not provide a response estimate, confidence interval, p-value, or other inferential analysis from which to judge precision. The absence of a reported result should not be mistaken for a result showing no effect, nor does it show that a treatment effect exists.

The serious adverse-event counts describe the numbers of participants affected in each group. They do not, without an analysis and appropriate uncertainty information, determine whether the groups differ. The reported serious-event terms and percentages likewise do not establish comparative risk because an arm-specific term breakdown is not provided. Death counts are not reported in the registry record.

In general, a Phase II trial can provide preliminary evidence and inform further investigation, but its label alone does not determine the strength of evidence. The record gives no reason for the terminated status, no explanation beyond insufficient data for the unreported progression-free-survival outcome, and no sample-size justification. These absences limit what can be inferred about the trial's conduct and its ability to answer the original question.

The narrow interpretation is that the record documents the trial's design and some safety observations, while leaving its primary response result unavailable. No conclusion about the efficacy or comparative safety of the regimens follows from the posted information alone.

13. Why This Trial Matters Statistically

This trial matters statistically because it illustrates the difference between an endpoint being named and its result being available. Best response is designated as the primary outcome, with a clear assessment period and a defined population requiring baseline and post-baseline scans. Yet response counts and analyses are not reported in the registry record. A well-defined endpoint is necessary for interpretation, but it cannot replace the result itself.

The record also distinguishes the original primary outcome, progression-free survival, from the best-response outcome ultimately listed. It states that there was insufficient data to report progression-free survival. These are distinct estimands: one concerns the best recorded response, and the other concerns time to an event under the endpoint definition. Keeping that distinction explicit avoids treating one as a numerical substitute for the other.

The safety information shows why denominators and analysis details matter. Serious adverse-event counts are available for both groups, but the record does not provide uncertainty estimates or a comparative analysis. The event-term percentages are not broken down by arm, and death counts are not posted. Clear reporting of populations, outcome definitions, denominators, and uncertainty is essential when readers assess descriptive safety data.

Finally, the terminated status and the absence of a reported sample-size justification or analysis plan leave important questions unanswered. The record does not state why the trial was terminated or how missing assessments were handled. This does not establish that any particular design or analysis decision was inappropriate; it identifies limits on what readers can infer. Statistically, the case underscores that transparent reporting of outcomes and analysis methods is needed to make even a randomized study's findings interpretable.

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 is that the primary outcome is named but its results are not reported in the registry record. There are no best-response counts by group, effect estimates, confidence intervals, or test results. The original primary outcome, progression-free survival, is also not reported; the record only states that insufficient data were available. The reason for that insufficiency is not given.

The registry lists the trial as terminated but does not report why it ended. It does not provide a sample-size justification, a detailed statistical analysis plan, or information about interim analyses. The record identifies the study as randomized and open-label, but does not describe allocation procedures, masking of any outcome assessment, or the detailed conduct of response review.

The primary-outcome population requires at least one baseline and one post-baseline scan, but the number meeting this condition and the handling of missing scans are not reported. There is no description of imputation, sensitivity analyses, or a broader analysis population. The detailed arm descriptions are blank, and treatment doses and schedules are not reported in the registry record.

Safety reporting is also incomplete for comparative interpretation. Serious adverse-event counts are available, but no uncertainty estimates or tests are reported. The listed serious-event terms do not have arm-specific breakdowns in the record, and death counts are not reported. Follow-up duration and exposure-adjusted safety analyses are not reported. These gaps constrain interpretation but do not, by themselves, establish the presence or absence of a treatment difference.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: A Study of Sunitinib in Combination With Bevacizumab and Paclitaxel in Previously Untreated Patients With Metastatic Breast Cancer (SABRE-B) — NCT00434356.
• Registry record last updated 2009-12-03; status last verified 2009-11.
• Results first posted 2009-12-03.
• 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

NCT00434356 is a multicenter, randomized, controlled, open-label, parallel-group Phase II trial of sunitinib with bevacizumab and paclitaxel in previously untreated patients with metastatic breast cancer. Enrollment was 46, and the status is terminated. The registry record gives a start date of 2007-03 and a primary completion date of 2008-05.

The posted primary outcome is best response by RECIST, assessed from randomization until disease progression or recurrence. The record says progression-free survival was the original primary outcome but could not be reported because data were insufficient. Best-response results are not reported in the registry record.

Serious adverse events affected 10 of 23 participants in the three-drug group and 9 of 23 in the bevacizumab-plus-paclitaxel group. The reason for termination, primary efficacy estimates, analysis plan, and handling of missing scans are not reported in the registry record.