This page provides an independent statistical analysis and educational interpretation of publicly reported results. ClinicalTrials.gov provides the official trial registry record. Numerical trial results on this page are restricted to the results posted in the ClinicalTrials.gov record; calculations added by Clinical Biostats are labelled as such.
1. Trial at a Glance
This page covers the registry results for Bevacizumab Given With Either Anastrozole or Fulvestrant With Trastuzumab for Postmenopausal Metastatic Breast Cancer (NCT00405938), a randomized phase 2 study. The primary outcome is Progression Free Survival (PFS), the Length of Time, in Months, That Patients Were Alive From Their First Date of Protocol Treatment Until Worsening of Their Disease.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT00405938 |
| Phase | Phase 2 |
| Condition | Breast Cancer, Breast Neoplasms |
| Allocation | Randomized |
| Design model | Parallel |
| Masking | None (open label) |
| Enrollment | 79 |
| Arms in the primary outcome | 2 |
| Lead sponsor | SCRI Development Innovations, LLC |
| Results posted | Yes |
2. Clinical Question
Population
Postmenopausal patients with hormone receptor-positive metastatic breast cancer. The trial description specifies trastuzumab for patients with HER2-positive disease.
Intervention
Bevacizumab with anastrozole.
Comparator
Bevacizumab with fulvestrant.
Primary question
How did progression-free survival, measured from first protocol treatment until disease progression or death, compare between the two regimens?
The registry record describes an open-label, randomized, parallel phase II trial. Both groups received bevacizumab, while the endocrine treatment differed: anastrozole in one group and fulvestrant in the other. Trastuzumab was included for HER2-positive patients, according to the official trial description. The record does not describe a separate group receiving neither bevacizumab nor endocrine therapy.
The primary endpoint was progression-free survival (PFS), defined as the interval from first treatment to disease progression or death, whichever occurred first. The record also includes objective response rate as a secondary endpoint. This makes the clinical question broader than whether tumors showed an objective response: it also asks how long patients remained alive without recorded progression.
The comparison is between treatment combinations in the trial population, not between either combination and an untreated group. The registry record does not report enough detail to establish how the results might apply to populations outside the stated postmenopausal, hormone receptor-positive metastatic setting, or to treatment approaches not included in the trial.
3. Trial Design
This was a phase II, randomized, open-label trial with a parallel-group design. The registry record lists enrollment of 79 and marks the study as completed. The recorded start is 2006-11, and primary completion is recorded as 2010-06. The record does not report the method used to generate or conceal the random allocation sequence.
One group received bevacizumab with anastrozole; the other received bevacizumab with fulvestrant. The official title describes trastuzumab for HER2-positive patients. Thus, the endocrine treatment was the main stated difference between the groups, while the record allows additional HER2-directed treatment for the specified subgroup. The arm descriptions include bevacizumab dosing information, but the fulvestrant description in the registry record is incomplete. Treatment details beyond what is recorded should not be inferred.
The arm-level PFS results list 38 patients for bevacizumab/anastrozole and 41 for bevacizumab/fulvestrant. The record gives median PFS estimates of 21 months and 9 months, respectively. For the first group, the reported confidence interval has a lower limit of 14 months, with no upper limit reported. For the second group, the interval is 5 to 13 months.
Open-label means that masking was not used, according to the registry record. This may be relevant to outcomes that involve clinical judgment or decisions about when to assess or record progression. The record does not report the progression-assessment schedule, independent review procedures, or blinding of endpoint assessment. It also does not report a statistical analysis plan, the randomization details, or a sample-size justification.
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
| Stage | Bevacizumab/Anastrozole | Bevacizumab/Fulvestrant |
|---|---|---|
| STARTED | 38 | 41 |
| COMPLETED | 38 | 41 |
| NOT COMPLETED | 0 | 0 |
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.
| Characteristic | Unit | Bevacizumab/Anastrozole | Bevacizumab/Fulvestrant | Total |
|---|---|---|---|---|
| Participants analysed | 38 | 41 | 79 | |
| Age, Continuous | years | 62 (37 to 85) | 63 (48 to 88) | 63 (37 to 88) |
| Sex: Female, Male: Female | Participants | 38 | 41 | 79 |
| Sex: Female, Male: Male | Participants | 0 | 0 | 0 |
| Region of Enrollment: United States | participants | 38 | 41 | 79 |
6. Primary Endpoint
The registry lists the primary outcome as Progression Free Survival (PFS), the Length of Time, in Months, That Patients Were Alive From Their First Date of Protocol Treatment Until Worsening of Their Disease, measured over 18 months.
| Element | Registry entry |
|---|---|
| Result type | Median |
| Measure of spread | 95% Confidence Interval |
| Unit | months |
| Endpoint classification | Time-to-Event Analysis |
The primary endpoint was progression-free survival, measured in months from the date of first protocol treatment to disease progression or death, whichever occurred first. A patient’s PFS time therefore ends at the earlier of those events. The registry record gives an 18-month timeframe for the endpoint.
Time-to-event endpoints are useful when the timing of an event matters and when participants may have different lengths of follow-up. Rather than reducing the outcome to whether progression occurred by one fixed date, the endpoint incorporates the observed timing of progression or death. The median is the point in the estimated event-time distribution at which half of the group’s observed time-to-event experience lies on either side. It is a group summary, not a prediction of an individual patient’s course.
The registry record reports a median and a 95% confidence interval for each group, though the upper confidence limit is not reported for the anastrozole group. A confidence interval conveys uncertainty around the estimated median; a wider interval indicates less precision than a narrower one. The record does not report a sponsor-conducted comparative hazard ratio or a statistical test for PFS. Therefore, the arm-specific medians alone do not establish the size or statistical certainty of a difference between regimens.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The posted primary results show a median PFS of 21 months for bevacizumab/anastrozole and 9 months for bevacizumab/fulvestrant. The reported 95% confidence interval for the first group has a lower limit of 14 months; its upper limit is not reported in the registry record. For the second group, the reported interval is 5 to 13 months. These are separate arm-level estimates, not a direct estimate of the treatment contrast.
The median estimates are numerically different, but the registry record does not include a sponsor-reported hazard ratio, confidence interval for a comparative effect, or p-value for the primary endpoint. Without a reported comparative analysis, the observed medians cannot establish whether the regimens differ statistically, how large a comparative effect may be, or how precise that effect is. No recalculated primary comparison is presented because the record does not provide the necessary time-to-event information for such a calculation.
The confidence intervals also need to be read with care. The second group has both limits reported, while the first group has only its lower limit. The missing upper limit is not reported in the registry record; it should not be treated as though it were infinite, equal to another value, or known from the displayed median. The incomplete interval limits direct comparison of precision between the arm estimates.
These results describe the enrolled trial groups under the study’s recorded treatment conditions. The trial was open-label, and the registry record does not describe blinded endpoint review, progression-assessment timing, follow-up completeness, or handling of censoring. Those details matter for interpreting time-to-event estimates, but they are not reported in the registry record.
The registry also lists objective response rate as a secondary outcome. Secondary results can add context about tumor response, but they do not replace a comparative analysis of the primary time-to-event endpoint. Their interpretation depends on how many outcomes were examined and whether the analysis plan accounted for multiple testing; those details are not reported in the registry record. The posted results should therefore be read as descriptive arm-level evidence, with no claim that one regimen is superior or inferior based on the primary endpoint record alone.
9. Statistical Methods Explained
The statistical results in the registry record include arm-specific medians for the primary time-to-event endpoint and participant counts for the secondary response endpoint. These quantities answer different questions. A median summarizes the distribution of event times within a group, while a response count records how many participants met the response definition within the stated assessment period. Neither type of summary, by itself, is a complete comparative analysis.
What does a median PFS estimate convey?
In general, a time-to-event analysis uses both the timing of events and information about participants who have not yet had the event during their observed follow-up. Such participants may be censored: their follow-up contributes information up to the last time their event status is known, without treating them as though an event occurred then. This distinction is important because participants may have different follow-up durations. The registry record does not report censoring counts or the method used to estimate the medians.
The median is a descriptive location in the estimated event-time distribution. It does not show the full shape of that distribution, whether treatment effects change over time, or the probability that a particular person will remain progression-free for a given duration. A hazard ratio, when reported, compares event rates over follow-up under a specified model; it is not the same quantity as a ratio or difference of medians. No sponsor-reported hazard ratio for PFS appears in the registry record.
How should confidence intervals be read?
In general, a confidence interval expresses uncertainty about an estimated quantity under the assumptions of the statistical procedure used. It is not a range containing a known fixed percentage of individual patient outcomes, and it does not directly provide the probability that the true value lies within the particular reported interval. For the first arm, only the lower confidence limit is recorded. Since the upper limit is absent, the reported interval is incomplete for judging the median’s precision. The registry record does not explain why that limit is missing.
Separate confidence intervals for two groups are not a substitute for an interval on the difference or ratio between groups. A direct comparative estimate would quantify the contrast and its uncertainty. For PFS, the registry record does not report such an estimate or an associated test. A numerical contrast derived from the two medians would not account for the underlying event-time data or censoring and should not be presented as a sponsor analysis.
What do the secondary comparisons mean?
The posted objective response results are counts of participants, with arm denominators recorded alongside them. The registry record also contains an unadjusted recalculation of the risk difference and its confidence interval and p-value. A risk difference expresses a difference in observed proportions between groups; an unadjusted calculation does not account for other variables or for any model-based adjustment. The posted interval extends from a negative value to a small positive value, so it includes zero. The unadjusted p-value is 0.058. These are exploratory summaries and are not a sponsor-reported analysis: the record lists no reported analyses for this outcome.
In general, a confidence interval for a risk difference that includes zero is compatible with no difference under the interval’s assumptions, while also allowing effects in either direction within the interval. A p-value describes how unusual data at least as discrepant as those observed would be under a specified null model; it is not the probability that the null hypothesis is true. An unadjusted p-value also does not account for the possibility that multiple outcomes or comparisons were considered.
What are the planning illustrations?
The posted planning illustrations use the observed secondary endpoint effect as a reference and show hypothetical participants per arm for 80% power and for 90% power when planning for 100%, 75%, or 50% of that observed effect. The assumptions stated in the registry record are a two-sided significance level of 0.05, equal allocation, and a normal approximation. These calculations are illustrations, not the trial’s own design justification and not observed power. They do not show that the original study was planned with these assumptions, nor do they establish that a future study would achieve the stated power. The sample-size justification for this trial is not reported in the registry record.
For time-to-event outcomes, planning generally concerns the number of events needed under assumptions about the comparison and analysis. The registry record notes an event-based convention for those planning calculations, but there is no primary PFS planning result or sponsor-reported PFS comparison in the posted analyses. The record also does not report interim analyses, adjustment for multiplicity, the primary analysis population, or the statistical methods used by the sponsor. These omissions limit what can be inferred about the prespecified analysis and the evidentiary status of each result.
10. Multiplicity, Missing Data and Analysis Populations
The registry record lists one primary outcome and a secondary objective response outcome, but it does not report a detailed statistical analysis plan. It does not state whether additional endpoints or subgroup analyses were planned, how many comparisons were considered, or whether any procedure was used to control the chance of false-positive findings across multiple analyses. Interim analyses are not reported in the registry record.
Multiplicity matters because the interpretation of an isolated p-value changes when several outcomes, time points, or subgroup comparisons are tested. Without a stated testing hierarchy or adjustment, secondary p-values should not be treated as confirmatory. The posted secondary comparison is unadjusted, and the registry record lists no reported analyses for it. The primary PFS result has no reported comparative test or hazard ratio.
The registry record also does not report how missing outcome data were handled, how many participants had incomplete follow-up, whether all randomized participants were included in each analysis, or the definition of the analysis population. It does not specify whether PFS was analyzed according to randomized group or another population definition. These are important details because exclusions, censoring, and missing assessments can affect both the estimated outcome and the group comparison.
Other methodological details not reported in the registry record include the randomization sequence and concealment, the sample-size justification, the progression-assessment schedule, and whether progression was reviewed independently or without knowledge of treatment assignment. Their absence does not establish that no procedures were used; it means the registry record does not document them. These limits make it difficult to assess how closely the posted summaries reflect a prespecified analysis.
11. Safety Results
The registry reports serious adverse events as affected participants divided by participants at risk.
| Arm | Participants with serious adverse events | Participants at risk | Percentage |
|---|---|---|---|
| Bevacizumab/Anastrozole | 10 | 38 | 26.3% |
| Bevacizumab/Fulvestrant | 12 | 41 | 29.3% |
Other (non-serious) adverse events
Participants with at least one non-serious event at or above the registry's 5% reporting threshold.
| Arm | Participants affected of at risk |
|---|---|
| Bevacizumab/Anastrozole | 38 of 38 |
| Bevacizumab/Fulvestrant | 41 of 41 |
Most frequent serious adverse event terms
| Event term | Organ system | Bevacizumab/Anastrozole | Bevacizumab/Fulvestrant |
|---|---|---|---|
| Dyspnea | Respiratory, thoracic and mediastinal disorders | 3 of 38 | 0 of 41 |
| CNS Ischemia | Nervous system disorders | 1 of 38 | 1 of 41 |
| Syncope | Nervous system disorders | 0 of 38 | 1 of 41 |
| cTnI | Cardiac disorders | 0 of 38 | 1 of 41 |
| Superventricular Arrhythmia - Sinus Bradycardia | Cardiac disorders | 1 of 38 | 0 of 41 |
| Infection - Pneumonia | Infections and infestations | 0 of 38 | 1 of 41 |
| Dehydration | Gastrointestinal disorders | 0 of 38 | 1 of 41 |
| Renal Failure | Renal and urinary disorders | 0 of 38 | 1 of 41 |
| Failure to Thrive | Metabolism and nutrition disorders | 0 of 38 | 1 of 41 |
| Seizure | Nervous system disorders | 0 of 38 | 1 of 41 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Bevacizumab/Anastrozole | Bevacizumab/Fulvestrant |
|---|---|---|---|
| Fatigue | General disorders | 22 of 38 | 30 of 41 |
| Hypertension | Cardiac disorders | 18 of 38 | 20 of 41 |
| Proteinuria | Metabolism and nutrition disorders | 13 of 38 | 18 of 41 |
| Nausea | Gastrointestinal disorders | 14 of 38 | 12 of 41 |
| Hemoglobin | Blood and lymphatic system disorders | 13 of 38 | 12 of 41 |
| Pain - Limb | General disorders | 13 of 38 | 12 of 41 |
| Arthralgia | Musculoskeletal and connective tissue disorders | 13 of 38 | 10 of 41 |
| Hot Flashes | Endocrine disorders | 13 of 38 | 8 of 41 |
| Pain - Joint | General disorders | 11 of 38 | 10 of 41 |
| Pain - Head | General disorders | 17 of 38 | 3 of 41 |
Serious events with the highest arm-level rate: dyspnea (7.9%), superventricular arrhythmia - sinus bradycardia (2.6%), thrombosis/thrombus/embolism (2.6%), diarrhea (2.6%), ards (2.6%).
The registry record lists serious adverse events in both treatment groups. There were 10 affected participants among 38 at risk in the bevacizumab/anastrozole group and 12 among 41 at risk in the bevacizumab/fulvestrant group. The record also indicates that other, non-serious adverse events affected 38 of 38 and 41 of 41 participants, respectively. These are counts within each recorded safety group; they are not a direct comparison adjusted for follow-up or exposure.
The most frequently listed serious-event term is dyspnea at 7.9%. Other terms listed at 2.6% each are superventricular arrhythmia - sinus bradycardia, thrombosis/thrombus/embolism, diarrhea, ARDS, and CNS ischemia. The registry record does not provide a comparative statistical analysis of these events or information sufficient to determine whether an event was caused by a treatment.
Deaths are not reported in the registry record. Serious and other adverse event counts should be interpreted as recorded safety summaries, not as evidence that a regimen is safe or unsafe. Differences in observation time and event reporting are not described.
12. What the Result Does, and Does Not, Mean
The posted primary results describe median progression-free survival in each randomized group. The median was 21 months with bevacizumab/anastrozole and 9 months with bevacizumab/fulvestrant. The confidence interval is incomplete for the first estimate, and the registry record does not report a comparative hazard ratio, confidence interval for a treatment contrast, or primary-endpoint p-value. These findings therefore describe the observed arm-level summaries but do not establish a statistically supported difference between the regimens.
The trial’s randomized design provides a framework for comparing the two combinations, but the information in the registry record is not sufficient to assess all features of that comparison. In particular, the record does not document the allocation procedures, analysis population, missing-data handling, censoring details, progression-assessment process, or a full sponsor analysis. Those omissions constrain interpretation of both the size and reliability of any apparent difference.
The findings do not show how either regimen compares with no treatment or with another standard regimen, because no such group is listed. They also do not establish effects in populations outside the postmenopausal, hormone receptor-positive metastatic setting described in the trial record. The mention of trastuzumab for HER2-positive patients indicates that treatment could vary by HER2 status, but subgroup-specific results are not reported.
The secondary response outcome adds descriptive context, but its unadjusted recalculation is not a substitute for a prespecified and reported primary comparison. The absence of documented multiplicity procedures and analysis details means that secondary findings should be interpreted cautiously. Taken together, the registry record supports a description of the groups and their posted outcomes, while leaving important questions about comparative effect, precision, and analysis conduct unresolved.
13. Why This Trial Matters Statistically
This trial is statistically informative as an example of why arm-level summaries and comparative evidence are not interchangeable. A median PFS in each group provides a compact description of time-to-event experience, but readers need a direct comparative estimate and its uncertainty to assess the contrast. The registry record reports the medians but not a sponsor-reported hazard ratio or inferential analysis for the primary endpoint.
The record also illustrates the limits of an incomplete confidence interval. One arm’s upper confidence limit is not reported, so the displayed interval cannot fully communicate uncertainty around that median. Comparing two estimates using their separate summaries alone can suggest a pattern, but does not quantify the uncertainty of the difference between them.
Its randomized, parallel-group structure is relevant to the intended comparison of two combinations, while the open-label designation and lack of detail about endpoint assessment leave questions about how outcomes were assessed. The registry record’s secondary outcome and unadjusted recalculation further demonstrate why endpoint hierarchy and multiplicity matter: exploratory comparisons may help frame questions, but should not be elevated to confirmatory conclusions without a documented analysis plan.
Finally, the posted planning illustrations are explicitly hypothetical, based on an observed secondary effect and stated assumptions. They are not observed power and do not reveal the original sample-size rationale. Keeping these distinctions clear helps readers separate recorded outcomes, recalculated summaries, and planning scenarios.
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.
Several limitations are specific to what the registry record documents for this trial. The PFS results are reported as separate medians, but there is no sponsor-reported comparative hazard ratio, confidence interval for the between-group effect, or test. One arm’s 95% confidence interval lacks an upper limit, restricting assessment of the precision of that median.
The record describes an open-label study, but does not report how progression was assessed, how often assessments occurred, whether an independent review was used, or whether assessors were blinded. These details are relevant to a progression endpoint. The record also does not report censoring counts, follow-up completeness, missing-data procedures, or the analysis population.
Allocation is described as randomized, but the method of sequence generation and allocation concealment is not reported. A sample-size justification, interim-analysis information, and a detailed statistical analysis plan are also not reported. The record does not explain the missing upper confidence limit or document how the primary endpoint analysis was carried out.
The secondary response comparison is an unadjusted recalculation rather than a reported sponsor analysis. Multiplicity handling is not reported, so its inferential weight is limited. In addition, the trial description includes trastuzumab for HER2-positive patients, but subgroup-specific outcome results are not reported. These limitations apply to interpretation of the registry record and do not establish that the unreported procedures or analyses were absent from the trial itself.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Bevacizumab Given With Either Anastrozole or Fulvestrant With Trastuzumab for Postmenopausal Metastatic Breast Cancer — NCT00405938.
- Registry record last updated 2021-11-18; status last verified 2021-11.
- Results first posted 2013-02-15.
- 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.
Continue through the Clinical Biostats statistical pathway
Use this trial's endpoint as a starting point for deeper study of effect measures, confidence intervals, and sample-size planning.
18. Record Summary
This completed, open-label, randomized, parallel phase II trial enrolled 79 patients with postmenopausal hormone receptor-positive metastatic breast cancer. The two treatment groups received bevacizumab with either anastrozole or fulvestrant; the trial description specifies trastuzumab for HER2-positive patients.
The primary endpoint was PFS from first treatment until progression or death. The registry record reports arm-specific medians and confidence intervals, but no sponsor-reported comparative PFS analysis. Objective response rate is listed as a secondary outcome, with an unadjusted recalculation that should be treated as exploratory. Important analysis details, including the statistical plan, handling of missing data, and multiplicity procedures, are not reported in the registry record.