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 Nab-Paclitaxel and Bevacizumab Followed By Bevacizumab and Erlotinib in Metastatic Breast Cancer (NCT00733408), a na phase 2 study. The primary outcome is Progression-free Survival (PFS).
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT00733408 |
| Phase | Phase 2 |
| Condition | Estrogen Receptor-negative Breast Cancer, HER2-negative Breast Cancer, Progesterone Receptor-negative Breast Cancer |
| Allocation | Not applicable (single group) |
| Design model | Single Group |
| Masking | None (open label) |
| Enrollment | 59 |
| Arms in the primary outcome | n/a |
| Lead sponsor | University of Washington |
| Results posted | Yes |
2. Clinical Question
Population
People with metastatic or advanced breast cancer, in a study whose title and recorded conditions identify triple-negative disease and estrogen receptor-negative, progesterone receptor-negative, and HER2-negative breast cancer. The registry record does not give a fuller eligibility description in the primary endpoint population field.
Intervention
Induction treatment with nab-paclitaxel and bevacizumab, followed by maintenance treatment with bevacizumab and erlotinib. The registry summary describes this treatment sequence; the maintenance schedule is not reported in the registry record.
Comparator
There is no concurrent comparison group. The study is recorded as single-group, with allocation listed as not applicable and no masking. The protocol description refers to paclitaxel and bevacizumab as a benchmark for interpreting results, but that is not a randomized control arm in this trial.
Primary question
What is the median progression-free survival, measured from registration to documented progression, symptomatic deterioration, or death from any cause? The registry record gives the planned endpoint definition and analysis approach, but the primary endpoint result is not reported in the registry record.
The trial evaluates a sequence rather than a single treatment period: a chemotherapy and antibody induction phase is followed by maintenance therapy with targeted drugs. Its primary question concerns the time until progression or another specified event, not a direct comparison between two assigned treatment groups. The registry lists overall survival, response, adverse events, tumor expression, and circulating cell measures as additional outcomes. These outcomes provide different kinds of information, but their results and analysis details are not reported in the registry record.
3. Trial Design
This completed phase II study is recorded as a single-group trial with no masking. Allocation is listed as not applicable, and the registry enrollment is 59. The sponsor is the University of Washington. The recorded start date is 2008-04-23, and the primary completion date is 2017-07-05. These design details describe the study structure; they do not establish how many participants contributed data to any particular endpoint.
The treatment sequence begins with induction therapy. The arm description states that participants receive intravenous nab-paclitaxel on days 1, 8, and 15 and intravenous bevacizumab over 30-90 minutes on days 1 and 15. Treatment repeats every 28 days for 6 courses in the absence of disease progression or unacceptable toxicity. The record describes maintenance treatment with bevacizumab and erlotinib, but the available arm description is incomplete and its maintenance schedule is not reported in the registry record.
Because there is no concurrent control group, the study can describe outcomes among participants treated under this regimen but cannot, on its own, establish a randomized treatment contrast. The primary endpoint description mentions paclitaxel and bevacizumab as a comparison benchmark for judging whether the treatment sequence might be promising. That benchmark is not a like-for-like control within this trial. Differences between this study's results and results from another setting could reflect population, follow-up, measurement, or other design differences, as well as treatment.
The registry lists the study as completed and identifies several additional outcomes, including overall survival, response, adverse events, tumor biomarker expression, and circulating tumor and endothelial cell measures. Detailed analysis results for these outcomes are not reported in the registry record.
4. Participant Flow and Accounting
The registry reports how participants moved through each stage of the study. All counts below are exactly as posted; missing counts are not inferred from other stages.
Overall Study
| Stage | Tx (Chemo, MoAb, and Enzyme Inhibitor) |
|---|---|
| STARTED | 59 |
| COMPLETED | 55 |
| NOT COMPLETED | 4 |
Reasons for not completing this period:
| Reason | Tx (Chemo, MoAb, and Enzyme Inhibitor) |
|---|---|
| Adverse Event | 4 |
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 | Tx (Chemo, MoAb, and Enzyme Inhibitor) |
|---|---|---|
| Participants analysed | 55 | |
| Age, Continuous | years | 55.3 (SD 12.5) |
| Sex: Female, Male: Female | Participants | 55 |
| Sex: Female, Male: Male | Participants | 0 |
| Ethnicity (NIH/OMB): Hispanic or Latino | Participants | 6 |
| Ethnicity (NIH/OMB): Not Hispanic or Latino | Participants | 47 |
| Ethnicity (NIH/OMB): Unknown or Not Reported | Participants | 2 |
| Race (NIH/OMB): American Indian or Alaska Native | Participants | 2 |
| Race (NIH/OMB): Asian | Participants | 1 |
| Race (NIH/OMB): Native Hawaiian or Other Pacific Islander | Participants | 0 |
| Race (NIH/OMB): Black or African American | Participants | 2 |
| Race (NIH/OMB): White | Participants | 47 |
| Race (NIH/OMB): More than one race | Participants | 1 |
| Race (NIH/OMB): Unknown or Not Reported | Participants | 2 |
6. Primary Endpoint
The registry lists the primary outcome as Progression-free Survival (PFS), measured over Time from date of registration to date of first documentation of progression or symptomatic deterioration or death due to any cause, assessed up to 8 years.
| Element | Registry entry |
|---|---|
| Result type | Median |
| Measure of spread | 95% Confidence Interval |
| Unit | Months |
| Endpoint classification | Time-to-Event Analysis |
The primary endpoint is progression-free survival (PFS), reported as a median time in months with a 95% confidence interval. Its clock starts at the date of registration and ends at the first documentation of progression, symptomatic deterioration, or death from any cause. Follow-up for this endpoint is described as extending up to 8 years.
Progression is defined using RECIST v1.0: a 20% increase in the sum of the longest diameters of target lesions, a measurable increase in a non-target lesion, or the appearance of new lesions. The endpoint therefore combines imaging-based evidence of progression with symptomatic deterioration and death. These events do not all have the same clinical meaning, but they are joined in a time-to-event measure to capture the time until the first specified event.
A median is useful for describing the point in the observed survival-time distribution by which the event has occurred for half of the relevant population, subject to the survival analysis and censoring. The confidence interval conveys uncertainty around that median; it does not show the range of individual participants' times. The registry describes Kaplan-Meier curves and a 95% confidence interval for the median. Neither the median PFS nor its confidence interval is reported in the registry record, so the endpoint's observed value and precision cannot be assessed from the record.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The registry record gives the study design, treatment sequence, endpoint definition, and planned approach to PFS analysis. It does not report a median PFS, a confidence interval for that median, or a primary endpoint estimate. Consequently, the posted registry information does not establish how long participants remained free of the defined events or how precisely that time was estimated.
The endpoint description states that a lower confidence bound greater than 8 months would be strong evidence against the protocol's stated benchmark, and that a median PFS of 13 months or greater could also be considered promising even if the confidence interval extended below 8 months. These statements are protocol criteria, not observed findings. The primary endpoint result needed to apply either criterion is not reported in the registry record. No conclusion about whether the study met those criteria can therefore be drawn from this record.
The single-group design is central to interpretation. It allows outcomes during the treatment sequence to be described, but it does not provide a randomized estimate of what would have happened to comparable participants under a different regimen. The benchmark named in the protocol does not supply a concurrent control group. Any contrast with an external estimate would require information about the source population and methods, and such a comparison would not have the protection against confounding that random assignment can provide.
The registry records enrollment of 59, while the safety summary lists 55 participants at risk for the adverse-event summaries. The reason for this difference, and the number included in the primary PFS analysis, are not reported in the registry record. The distinction matters: enrollment does not by itself establish the analysis population or the completeness of follow-up for a particular outcome.
The safety summary lists 5 participants with serious adverse events, 52 with other adverse events, and 3 deaths in the treatment group. These are descriptive counts, not estimates of comparative risk. The registry information presented does not identify whether the deaths were caused by treatment or disease, nor does it report a control-group rate. The serious adverse-event terms and percentages should likewise be read as reported event information rather than evidence about a treatment effect.
Overall, the record supports an account of the question the investigators planned to address and the framework used for PFS. Without the endpoint estimate and the associated analysis details, statistical precision, event patterns over time, and alignment with the protocol's stated thresholds remain unresolved.
9. Statistical Methods Explained
The primary endpoint is a time-to-event outcome. Such outcomes measure the time from a defined starting point until a specified event, rather than simply recording whether an event occurred by a single fixed assessment. In this trial, time begins at registration, and the event is the first documented progression, symptomatic deterioration, or death from any cause. The event definition and starting point determine what the estimated PFS represents.
How does Kaplan-Meier estimation work?
Kaplan-Meier estimation is a general method for describing time to an event when participants may have different lengths of follow-up. It uses the ordering of observed event times and accounts for participants whose event has not been observed by their last known follow-up. Those participants are censored at that point: their available information contributes up to that time, without treating them as if they had experienced the event. The registry says Kaplan-Meier survival curves will be used, but does not report the curve or explain the censoring rules used in the analysis.
Censoring requires care in interpretation. A participant who is censored is not known to have remained event-free indefinitely; the available observation only establishes the time through which the participant was followed without a recorded event. Kaplan-Meier estimates rely on assumptions about how censoring relates to future event experience. The registry record does not report diagnostics or sensitivity analyses assessing those assumptions.
What does the median and confidence interval convey?
The median PFS is a summary of the estimated time-to-event distribution. It is not an average follow-up time, nor does it describe the experience of every participant. A 95% confidence interval expresses uncertainty in the estimate under the statistical method: across repeated applications of the method under its assumptions, intervals constructed this way would capture the underlying parameter at the stated frequency. It is not a guarantee that the true value lies within a particular interval, and it is not an interval containing 95% of individual participant outcomes.
The record specifies a 95% confidence interval for the median PFS, but gives no estimate or interval. It also states that a lower bound greater than 8 months would be strong evidence relative to a protocol benchmark and that a median of 13 months or greater could be considered promising under another stated criterion. These are decision rules described in the protocol; they should not be mistaken for study results.
How is progression defined?
The registry uses RECIST v1.0 criteria. The definition includes a 20% increase in the sum of the longest diameters of target lesions, a measurable increase in a non-target lesion, or new lesions. In general, prespecified criteria can make outcome classification more consistent by identifying what counts as progression. The endpoint also includes symptomatic deterioration and death from any cause, so it is broader than radiographic progression alone. The record does not specify how symptomatic deterioration was operationalized or adjudicated.
The timeframe is described as assessment up to 8 years. A stated maximum follow-up window does not by itself tell readers how long participants were actually followed, how many events occurred, or whether follow-up was complete. Those details are not reported in the registry record.
What can a single-group analysis establish?
In general, a single-group time-to-event analysis can estimate the event-time distribution observed among participants in that group, subject to follow-up and analysis assumptions. It does not estimate a randomized contrast with another treatment. The protocol's reference to paclitaxel and bevacizumab is a benchmark, not a concurrent comparison arm. Differences from an external benchmark can be affected by differences in participants, outcome definitions, follow-up, and clinical practice, among other factors.
The study description also contains a planning criterion based on the confidence interval and a separate median threshold. These criteria can guide interpretation of an estimate, but they do not supply evidence in the absence of the estimate. No PFS analysis result is reported in the registry record.
How should planning illustrations be understood?
General sample-size calculations describe how much information a hypothetical design might need to detect a chosen effect under specified assumptions. The planning approach described for the illustrations uses a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation; the effect to detect is expressed as a stated fraction of the observed effect. For time-to-event illustrations, the quantity is a total event count. These are planning illustrations, not observed power and not a description of the actual single-group trial's design.
The method for a hypothetical two-arm calculation does not create a control arm in this trial. Nor does a planning illustration establish that the study had a particular probability of finding a result. Interpreting a calculation requires the underlying effect estimate and assumptions; the registry record does not report the PFS estimate that would allow readers to assess an effect-based illustration. The record also does not report a sample-size justification for the actual trial, so its design rationale should not be inferred from a planning illustration.
More broadly, statistical interpretation depends on the analysis population, event count, follow-up distribution, missing-data handling, and any deviations from the planned definitions. Those details, beyond the named Kaplan-Meier approach and confidence interval, are not reported in the registry record. As a result, the available description clarifies the intended methods but cannot establish how the final endpoint analysis was carried out.
10. Multiplicity, Missing Data and Analysis Populations
The registry lists several outcomes in addition to PFS: overall survival, response, adverse events assessed using National Cancer Institute CTCAE Version 3.0, EGFR and SPARC expression in the primary tumor, and changes in circulating tumor and endothelial cell levels. The record identifies PFS as primary, but a multiplicity strategy for interpreting the collection of outcomes is not reported in the registry record. Without a stated strategy, readers cannot determine whether and how the risk of false-positive findings across multiple outcome analyses was addressed.
Missing-data procedures are also not reported in the registry record. For PFS, this includes details about censoring and follow-up beyond the broad time-to-event description. For other outcomes, the record does not describe how missing measurements, incomplete assessments, or participants without evaluable data were handled.
The analysis populations are not reported in the registry record. The enrollment is 59, whereas the safety summary gives 55 participants at risk for its event summaries. The record does not explain the difference or identify the population used for the primary endpoint. It also does not state whether analysis populations differed by outcome or whether exclusions were made.
The registry describes Kaplan-Meier curves and a confidence interval for median PFS, but other aspects of the statistical analysis plan—including any interim analyses, model adjustments, or sensitivity analyses—are not reported in the registry record. Their absence from the record should not be interpreted as proof that they were or were not performed.
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 |
|---|---|---|---|
| Tx (Chemo, MoAb, and Enzyme Inhibitor) | 5 | 55 | 9.1% |
Deaths
| Arm | Deaths (participants affected of at risk) |
|---|---|
| Tx (Chemo, MoAb, and Enzyme Inhibitor) | 3 of 55 |
Other (non-serious) adverse events
Participants with at least one non-serious event at or above the registry's 2% reporting threshold.
| Arm | Participants affected of at risk |
|---|---|
| Tx (Chemo, MoAb, and Enzyme Inhibitor) | 52 of 55 |
Most frequent serious adverse event terms
| Event term | Organ system | Tx (Chemo, MoAb, and Enzyme Inhibitor) |
|---|---|---|
| Infection | Infections and infestations | 2 of 55 |
| Pain | Musculoskeletal and connective tissue disorders | 1 of 55 |
| Dyspnea | Respiratory, thoracic and mediastinal disorders | 1 of 55 |
| Muscle Weakness | Musculoskeletal and connective tissue disorders | 1 of 55 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Tx (Chemo, MoAb, and Enzyme Inhibitor) |
|---|---|---|
| Neutropenia | Blood and lymphatic system disorders | 16 of 55 |
| Fatigue | General disorders | 14 of 55 |
| Neuropathy | Nervous system disorders | 8 of 55 |
| Lymphopenia | Blood and lymphatic system disorders | 8 of 55 |
| Pain | Musculoskeletal and connective tissue disorders | 7 of 55 |
| Rash | Skin and subcutaneous tissue disorders | 4 of 55 |
| Anorexia | Metabolism and nutrition disorders | 3 of 55 |
| Dehydration | Metabolism and nutrition disorders | 3 of 55 |
| Hyponatremia | Metabolism and nutrition disorders | 3 of 55 |
| Infection | Infections and infestations | 3 of 55 |
Serious events with the highest arm-level rate: infection (3.6%), pain (1.8%), dyspnea (1.8%), muscle weakness (1.8%).
The safety summary lists 55 participants at risk. It reports 5 participants with serious adverse events and 52 with other adverse events, along with 3 deaths. These counts describe the registry's safety summary; they are not comparative estimates because this is a single-group trial with no concurrent control group. The registry record does not report the reason that the safety population differs from the enrollment of 59.
The listed serious adverse-event terms are Infection (3.6%), Pain (1.8%), Dyspnea (1.8%), and Muscle Weakness (1.8%). The record does not clarify whether participants could contribute to more than one term, or provide further event-level detail in these figures. The percentages should be interpreted as the registry's reported values, not recalculated or treated as a complete account of all event types.
The presence of 3 deaths in the safety summary does not establish their cause or attribution. Whether they were considered related to treatment, due to disease, or otherwise classified is not reported in the registry record. The adverse-event outcome is described as assessed using National Cancer Institute CTCAE Version 3.0, but the record does not provide further detail about severity grading, timing, duration, or handling of events. These figures are descriptive safety information and do not establish comparative safety.
12. What the Result Does, and Does Not, Mean
The record establishes that this was a completed phase II, single-group study of an induction and maintenance treatment sequence for metastatic breast cancer. It also sets out a PFS endpoint, defines progression using RECIST v1.0 alongside symptomatic deterioration and death, and describes Kaplan-Meier estimation with a 95% confidence interval for the median.
Those details explain what the study aimed to measure, but the primary PFS estimate and its confidence interval are not reported in the registry record. As a result, the record does not show the observed duration of PFS, the precision of that estimate, or whether the stated protocol criteria were met. The planned assessment timeframe of up to 8 years is not a substitute for actual follow-up or outcome results.
The study's single-group structure also limits what can be concluded. It can describe outcomes among the participants in the treatment group, but it does not provide a randomized comparison with paclitaxel and bevacizumab or another control regimen. The protocol's benchmark language therefore cannot be read as evidence of a direct treatment advantage. A comparison with external results would require careful attention to differences in populations, follow-up, and outcome definitions.
The safety counts provide descriptive information for the registry's reported safety population. They do not establish causality or comparative risk, and the record does not report attribution for the 3 deaths. The additional listed outcomes may address other aspects of survival, response, adverse events, biomarkers, and circulating cells, but their results are not reported in the registry record.
The most defensible interpretation is therefore limited: the record describes a treatment strategy and its planned evaluation, but does not provide the primary result needed to judge the observed PFS or its statistical precision. It also does not supply the analysis-population, missing-data, and multiplicity details needed for a fuller assessment of the reported outcomes.
13. Why This Trial Matters Statistically
This trial illustrates why a clearly defined endpoint is not the same as a reported result. The registry specifies PFS, its starting point, the event definition, and an intended Kaplan-Meier analysis with a confidence interval. These details make the intended statistical question understandable. However, without the median and interval, readers cannot assess the observed outcome or its precision.
It also highlights the importance of separating a protocol benchmark from a concurrent comparison. The protocol describes criteria for judging whether the treatment sequence might be promising relative to paclitaxel and bevacizumab. Yet the trial is single-group, with no randomized control arm. The benchmark can provide context for the study's rationale, but it does not create a controlled estimate of a treatment difference.
The safety summary provides another useful statistical distinction: counts in a treated group are descriptive, whereas comparative safety claims require an appropriate comparator and clear event definitions. The registry lists serious and other adverse-event counts and selected serious terms, but does not report attribution for deaths or detailed analysis methods.
Finally, the record shows why analysis populations, censoring, missing-data procedures, and multiplicity matter. These choices shape how endpoint estimates and supporting outcomes should be understood, yet they are not reported in the registry record. A statistical reading must distinguish what the protocol planned, what the design can establish, and what outcome information is actually available.
14. Limitations
- The posted summary statistics are the only data these results rest on; patient-level data, full protocols and statistical analysis plans are not available.
- Recalculated results are simple, unadjusted calculations from posted summaries. They do not replace the sponsor's prespecified analysis.
The primary limitation for interpreting efficacy is that the median PFS and its 95% confidence interval are not reported in the registry record. The record therefore does not permit assessment of the primary endpoint against the protocol's stated criteria. It also does not report the number of PFS events, the follow-up distribution, or the final analysis population.
The single-group design has no concurrent control, despite the protocol's reference to paclitaxel and bevacizumab as a benchmark. This limits causal interpretation and prevents a randomized estimate of a treatment contrast. The registry's allocation entry is not applicable, and masking is listed as none.
The treatment description is incomplete for maintenance therapy. The regimen is identified as bevacizumab and erlotinib after induction, but the schedule is not reported in the registry record. The primary endpoint population field is also blank, and further eligibility details are not available in the record.
For safety, the registry lists 55 participants at risk, while enrollment is 59; the reason for the difference is not reported. The record lists 3 deaths but does not report attribution. It also does not provide the analysis populations, missing-data procedures, multiplicity plan, interim analyses, or additional statistical-plan details beyond the stated PFS method. These omissions limit interpretation but do not establish what procedures may have been used outside the registry record.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Nab-Paclitaxel and Bevacizumab Followed By Bevacizumab and Erlotinib in Metastatic Breast Cancer — NCT00733408.
- Registry record last updated 2018-12-04; status last verified 2018-11.
- Results first posted 2018-12-04.
- 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.
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18. Record Summary
NCT00733408 is a completed phase II, single-group study sponsored by the University of Washington, with registry enrollment of 59. It evaluates induction nab-paclitaxel and bevacizumab followed by maintenance bevacizumab and erlotinib for metastatic breast cancer. The primary endpoint is median PFS from registration to documented progression, symptomatic deterioration, or death from any cause, with a 95% confidence interval and a stated assessment period of up to 8 years.
The record describes Kaplan-Meier analysis and RECIST v1.0 progression criteria but does not report the primary endpoint estimate. Its safety summary lists 55 participants at risk, 5 with serious adverse events, 52 with other adverse events, and 3 deaths. Analysis populations, missing-data procedures, multiplicity handling, and attribution of deaths are not reported in the registry record.