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 Phase III Study of Vinflunine Plus Capecitabine Versus Capecitabine Alone in Patients With Advanced Breast Cancer (NCT01953003), a randomized phase 3 study. The primary outcome is Progression Free Survival (PFS).
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT01953003 |
| Phase | Phase 3 |
| Condition | Malignant Neoplasm of Breast |
| Allocation | Randomized |
| Design model | Parallel |
| Masking | None (open label) |
| Enrollment | 112 |
| Arms in the primary outcome | n/a |
| Lead sponsor | Pierre Fabre Medicament |
| Results posted | Yes |
2. Clinical Question
Population
Patients with advanced breast cancer previously treated with an anthracycline and a taxane. The primary endpoint description specifies an intention-to-treat population comprising all randomized patients.
Intervention
Intravenous vinflunine plus oral capecitabine. The registry describes vinflunine at 280 mg/m² on day 1 of each 3-week cycle and capecitabine at 825 mg/m² twice daily for 14 consecutive days beginning on day 1, followed by 1 week of rest.
Comparator
Oral capecitabine alone, described as 1250 mg/m² twice daily for 14 consecutive days beginning on day 1 of each cycle, followed by 1 week of rest.
Primary question
Does the combination differ from capecitabine alone in progression-free survival, defined from randomization to documented progression or death from any cause? The comparative primary-endpoint result is not reported in the registry record.
The registry describes this as a multicenter, randomized, open-label Phase III study. Its stated rationale concerns patients with advanced breast cancer previously treated with an anthracycline and a taxane, a group described as having limited treatment options. The primary objective was to compare the combination with capecitabine alone for progression-free survival. Secondary objectives included response, disease control, overall survival, and safety.
The registry record lists enrollment as 112, while the study summary describes a planned total of 334 patients. Those figures refer to different aspects of the record and should not be treated as interchangeable. The record marks the study completed, but it does not report the primary endpoint comparison. Thus, the clinical question can be stated from the study objectives, but its answer cannot be established from the results recorded.
3. Trial Design
The study is described as a randomized, open-label, parallel-group Phase III trial. Randomization assigns participants to one of the treatment groups according to an allocation process; the registry does not report the precise sequence-generation or concealment procedures. Open-label means the record does not describe masking of participants or study personnel. The study is identified as multicenter in its summary.
The comparison was between intravenous vinflunine plus capecitabine and capecitabine alone. In the combination arm, vinflunine was scheduled at 280 mg/m² on day 1 of each cycle every 3 weeks, with capecitabine at 825 mg/m² twice daily for 14 consecutive days beginning on day 1, followed by 1 week of rest. In the capecitabine arm, the recorded dose was 1250 mg/m² twice daily for 14 consecutive days beginning on day 1, followed by 1 week of rest. These are the regimens described in the registry; treatment modifications and adherence are not reported in the registry record.
The registry lists enrollment of 112 and also includes a study-summary statement describing a planned total of 334. The record does not explain the relationship between those figures. It lists a start of 2013-09, primary completion of 2017-07, and status completed. These registry entries describe the study record and do not establish when any unreported analysis was conducted.
The primary endpoint was progression-free survival in the intention-to-treat population, defined as all randomized patients. Follow-up assessments for progression were described as occurring every 6 weeks from randomization, up to 3 years, until documented progression or death from any cause. The registry does not report allocation ratios, stratification factors, protocol deviations, the statistical analysis plan, or the number of participants included in an endpoint analysis. Those details 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 | Arm A : iv Vinflunine Plus Capecitabine | Arm B : Capecitabine |
|---|---|---|
| STARTED | 56 | 56 |
| COMPLETED | 0 | 1 |
| NOT COMPLETED | 56 | 55 |
Reasons for not completing this period:
| Reason | Arm A : iv Vinflunine Plus Capecitabine | Arm B : Capecitabine |
|---|---|---|
| Not treated | 0 | 1 |
| Progressive disease | 35 | 45 |
| Related Adverse events | 7 | 2 |
| Non-related adverse events | 0 | 2 |
| Protocol Violation | 0 | 1 |
| Withdrawal by Subject | 14 | 4 |
Analysis population for the primary outcome, as defined in the registry: The ITT population, comprised of all randomised patients
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 | Arm A : iv Vinflunine Plus Capecitabine | Arm B : Capecitabine | Total |
|---|---|---|---|---|
| Participants analysed | 56 | 56 | 112 | |
| Age, Categorical: <=18 years | Participants | 0 | 0 | 0 |
| Age, Categorical: Between 18 and 65 years | Participants | 55 | 54 | 109 |
| Age, Categorical: >=65 years | Participants | 1 | 2 | 3 |
| Sex: Female, Male: Female | Participants | 56 | 56 | 112 |
| Sex: Female, Male: Male | Participants | 0 | 0 | 0 |
| Race and Ethnicity Not Collected | Participants | — | — | 0 |
| Region of Enrollment: Singapore | participants | 4 | 5 | 9 |
| Region of Enrollment: China | participants | 49 | 46 | 95 |
| Region of Enrollment: Taiwan | participants | 3 | 5 | 8 |
| Menopausal status: Menopausal | Participants | 31 | 29 | 60 |
| Menopausal status: Non-Menopausal | Participants | 25 | 27 | 52 |
| Tumour site - primary cancer: Right Breast | Participants | 23 | 32 | 55 |
| Tumour site - primary cancer: Left Breast | Participants | 33 | 24 | 57 |
6. Primary Endpoint
The registry lists the primary outcome as Progression Free Survival (PFS), measured over progression date will be assessed evey 6 weeks starting from the randomization date until first documented progression or date of death from any cause whichever came first assessed up to 3 years.
| Element | Registry entry |
|---|---|
| Result type | Count Of Participants |
| Measure of spread | not applicable |
| Unit | Participants |
| Endpoint classification | Binary Endpoint |
Progression-free survival is a time-to-event endpoint: it records the time from randomization until the first of documented disease progression or death from any cause. The registry specifies that a participant without documented progression is censored at the last tumor assessment or last follow-up contact showing no progression. Censoring means that the event time is not observed during the available follow-up; the participant contributes information up to the recorded censoring time.
This endpoint is used to summarize how long participants remain alive without documented progression. It brings progression and death into a single outcome definition, rather than treating tumor response alone as the primary measure. That can be useful in trials where the study question concerns control of disease over follow-up. It also makes the timing and completeness of assessments important: the record describes progression assessments every 6 weeks, starting at randomization, up to 3 years.
The registry identifies the primary outcome as progression-free survival and describes its calculation, but the recorded outcome field is expressed as a count of participants. No comparative time-to-event estimate, event count, confidence interval, or significance test is reported in the registry record. The endpoint definition therefore clarifies what the trial intended to compare, but it does not provide evidence about the size or precision of any observed difference.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The registry record identifies progression-free survival as the primary endpoint and gives its event and censoring definitions. It does not report the comparative primary-endpoint result. In particular, the record contains no reported group-specific time-to-event estimates, treatment-effect estimate, confidence interval, or primary-endpoint significance test. The direction, magnitude, and precision of the primary comparison therefore cannot be interpreted from this record.
That absence matters statistically. A trial objective states what investigators intended to learn; it is not itself an outcome. Likewise, the completed status does not establish whether a treatment group had longer progression-free survival, whether any estimated difference was precise, or how compatible the data were with no difference. No conclusion about benefit or lack of benefit can be drawn from the endpoint definition or trial status alone.
The registry does report safety summaries. Serious adverse events were recorded for 15 of 56 participants at risk in the vinflunine-plus-capecitabine group and 7 of 55 at risk in the capecitabine group. Other adverse events were recorded for 54 of 56 and 46 of 55, respectively. The record also lists deaths as 26 and 32 in the two groups, respectively, but does not supply a definition, follow-up context, or attribution for that death field. These entries are descriptive counts, not estimates of the primary endpoint. They should not be substituted for a progression-free survival comparison.
The listed serious-event terms include abdominal pain, ileus, and febrile neutropenia at 3.6% each, and ALAT increased, ASAT increased, and chest discomfort at 1.8% each. The registry excerpt does not describe how these terms were selected or whether they represent all serious events. Their presence in the record does not supply a comparative statistical analysis.
The study summary describes a planned total enrollment of 334, whereas the registry enrollment entry is 112. The record does not explain the difference. Without reported endpoint results and further detail about the analysis, the main statistical conclusion is limited: the trial question and endpoint are documented, but the primary comparative evidence is not reported in the registry record.
9. Statistical Methods Explained
The registry describes a randomized, open-label, parallel-group study. Random allocation is intended to make treatment groups comparable on average at the start of a study, including with respect to measured and unmeasured characteristics. That is a general property of randomization, not evidence that every possible imbalance was absent in this trial. The record does not report the randomization procedure, allocation concealment, stratification, or any checks of baseline balance.
What does an open-label design mean?
Open-label means masking was not used, as recorded for this study. In general, knowledge of treatment assignment can affect participant reports, clinical management, or judgments about outcomes. Progression-free survival includes a progression assessment, so consistency in assessment procedures can matter. The registry describes assessments every 6 weeks but does not report independent review, blinded assessment, or other procedures intended to reduce assessment bias. It is not possible to infer which procedures were or were not used beyond the information recorded.
How should progression-free survival be understood?
In general, time-to-event analysis uses both whether an event occurred and when it occurred. Here, the stated event is the first documented progression or death from any cause after randomization. A participant with no documented progression is censored at the last tumor assessment or follow-up contact showing no progression. Censoring is not the same as an event; it indicates that the event time is not observed beyond that point. Valid interpretation of a time-to-event comparison generally depends on how follow-up and censoring operate. The registry provides the censoring definition but does not report a censoring summary or checks of assumptions.
Common general approaches to comparing time-to-event outcomes include comparing survival curves or estimating a relative event rate. These methods have assumptions and answer related but not identical questions. The specific estimator, model, test, covariates, and assumptions used for the primary analysis are not reported in the registry record, so none should be attributed to this trial.
What does the intention-to-treat population indicate?
The registry defines the primary population as all randomized patients. In general, an intention-to-treat approach analyzes participants according to randomized assignment, regardless of whether they completed or followed the assigned treatment exactly. This preserves the comparison created by randomization and reflects assignment to a treatment strategy. The record does not report how many randomized patients had usable endpoint information, how missing assessments were handled, or whether additional analysis populations were used.
How should event counts and uncertainty be interpreted?
For a time-to-event estimate, a confidence interval describes statistical uncertainty around the estimated effect under the analysis method. A narrow interval indicates greater precision than a wide interval, while either interval must be interpreted in the context of the outcome and study design. No primary-endpoint estimate or confidence interval is reported, so precision cannot be assessed. A p-value, if reported, would address compatibility between data and a specified null hypothesis under the test assumptions; it would not measure the probability that a treatment is effective. No primary-endpoint p-value is reported.
The safety entries are counts of participants with events and the numbers at risk. Such counts are descriptive. General comparisons of event frequency may require clear event definitions, consistent observation periods, and appropriate uncertainty estimates. The record supplies no inferential comparison for these safety counts, and the counts alone do not adjust for differences in follow-up or characterize event timing.
What do the planning assumptions mean?
The registry describes a planning illustration based on the observed effect, using a two-sided significance level of 0.05, equal allocation, and a normal approximation, with the target effect set as a stated fraction of the observed effect. In general, this type of illustration asks what sample size would be needed under chosen assumptions; it is not an observed trial result and is not observed power. For time-to-event outcomes, the description refers to total events, while other outcomes are described in terms of participants per arm. No numerical planning estimates are reported in the registry record. The trial's own sample-size justification and design assumptions are not reported in the registry record.
Overall, the statistical methods that can be described with confidence are the randomized, open-label design, the intended intention-to-treat population, and the endpoint and censoring definitions. The detailed analysis plan, including the primary test or model and handling of incomplete data, is not reported in the registry record.
10. Multiplicity, Missing Data and Analysis Populations
The study summary lists several secondary objectives: response rate, time to response, duration of response, disease control rate, duration of disease control, overall survival, and safety. Assessing multiple outcomes can raise multiplicity concerns. In general, when many hypotheses are tested, the chance of at least one apparently notable result can increase unless the analysis plan addresses the number and ordering of tests. The registry record does not report a multiplicity adjustment, testing hierarchy, or prespecified strategy for interpreting secondary outcomes. This does not establish that no strategy existed; it means it is not reported in the registry record.
The primary analysis population is described as the intention-to-treat population, comprising all randomized patients. The record does not report missing endpoint data, losses to follow-up, exclusions from analysis, or how incomplete assessments were handled beyond the stated censoring definition. It also does not report sensitivity analyses for missing or potentially informative follow-up. These omissions limit assessment of whether the recorded analysis population and follow-up fully support the intended comparison.
The registry identifies a primary endpoint but does not report its comparative analysis. The detailed statistical analysis plan, including the model, test, covariate adjustment, handling of protocol deviations, and any interim analyses, is not reported in the registry record. Accordingly, the registry does not permit evaluation of how multiplicity or missing information was handled in the trial's primary or secondary analyses.
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 |
|---|---|---|---|
| Arm A : iv Vinflunine Plus Capecitabine | 15 | 56 | 26.8% |
| Arm B : Capecitabine | 7 | 55 | 12.7% |
Deaths
| Arm | Deaths (participants affected of at risk) |
|---|---|
| Arm A : iv Vinflunine Plus Capecitabine | 26 of 56 |
| Arm B : Capecitabine | 32 of 55 |
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 |
|---|---|
| Arm A : iv Vinflunine Plus Capecitabine | 54 of 56 |
| Arm B : Capecitabine | 46 of 55 |
Most frequent serious adverse event terms
| Event term | Organ system | Arm A : iv Vinflunine Plus Capecitabine | Arm B : Capecitabine |
|---|---|---|---|
| Abdominal Pain | Gastrointestinal disorders | 2 of 56 | 0 of 55 |
| Ileus | Gastrointestinal disorders | 2 of 56 | 0 of 55 |
| Febrile neutropenia | Blood and lymphatic system disorders | 2 of 56 | 0 of 55 |
| Intestinal obstruction | Gastrointestinal disorders | 1 of 56 | 0 of 55 |
| Mouth ulceration | Gastrointestinal disorders | 1 of 56 | 0 of 55 |
| Leukopenia | Blood and lymphatic system disorders | 1 of 56 | 0 of 55 |
| Neutropenia | Blood and lymphatic system disorders | 1 of 56 | 0 of 55 |
| Thrombocytopenia | Blood and lymphatic system disorders | 1 of 56 | 0 of 55 |
| Fatigue | General disorders | 1 of 56 | 0 of 55 |
| Pain | General disorders | 1 of 56 | 0 of 55 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Arm A : iv Vinflunine Plus Capecitabine | Arm B : Capecitabine |
|---|---|---|---|
| Nausea | Gastrointestinal disorders | 13 of 56 | 12 of 55 |
| Weight decreased | Investigations | 14 of 56 | 9 of 55 |
| Fatigue | General disorders | 14 of 56 | 9 of 55 |
| Constipation | Gastrointestinal disorders | 19 of 56 | 3 of 55 |
| Palmer-plantar erythrodysaesthesia | Skin and subcutaneous tissue disorders | 5 of 56 | 17 of 55 |
| Weight increased | Investigations | 4 of 56 | 13 of 55 |
| Abdominal pain | Gastrointestinal disorders | 13 of 56 | 3 of 55 |
| Vomiting | Gastrointestinal disorders | 11 of 56 | 4 of 55 |
| Neuropenia | Blood and lymphatic system disorders | 11 of 56 | 4 of 55 |
| Stomatitis | Gastrointestinal disorders | 10 of 56 | 3 of 55 |
Serious events with the highest arm-level rate: abdominal pain (3.6%), ileus (3.6%), febrile neutropenia (3.6%), alat increased (1.8%), asat increased (1.8%).
The registry reports serious adverse events for 15 of 56 participants at risk in the vinflunine-plus-capecitabine group and 7 of 55 at risk in the capecitabine group. It reports other adverse events for 54 of 56 and 46 of 55, respectively. These are participant counts with an event and the corresponding numbers at risk, as recorded. They are descriptive entries; the registry does not provide a comparative statistical test or uncertainty interval for these counts.
The listed serious-event terms are abdominal pain, ileus, and febrile neutropenia at 3.6% each, followed by ALAT increased, ASAT increased, and chest discomfort at 1.8% each. The record does not specify the full event-selection procedure or the observation time associated with these terms. The listed terms should therefore be read as the serious events highlighted in the registry, not necessarily as a complete account of every event experienced.
The death entries are 26 in the combination group and 32 in the capecitabine group. The record does not report their definition, timing, or relationship to treatment. These counts cannot be interpreted as progression-free survival results. The safety figures describe recorded events; by themselves, they do not establish a causal relationship or resolve differences in exposure and follow-up.
12. What the Result Does, and Does Not, Mean
The record establishes the study question, the randomized comparison, the primary endpoint definition, and several safety counts. It does not report the comparative progression-free survival result. Therefore, it cannot show from the registry record whether the groups differed in progression-free survival, how large any difference was, or how precisely it was estimated.
The endpoint was defined as time from randomization to documented progression or death from any cause, with censoring for participants without progression at their last assessment or qualifying follow-up contact. This definition is clinically and statistically distinct from a simple response count or a count of adverse events. Safety counts and death entries cannot stand in for the specified time-to-event comparison.
The record also should not be read as proving that no difference existed. An absent estimate is not an estimate of zero, and absence of a reported p-value is not evidence that a test was nonsignificant. Without the primary comparison and its uncertainty, the direction and precision of the result remain unknown in the registry record.
The registry lists enrollment as 112 and describes a planned total of 334 in the study summary, without explaining the relationship between those entries. It marks the study completed, but completion status does not fill the gap in reported efficacy results. The listed adverse-event and death counts provide limited descriptive information; definitions, follow-up context, and comparative analyses are not reported in the registry record.
Consequently, the defensible interpretation is narrow: the trial was designed to compare the combination regimen with capecitabine alone in the stated population, using progression-free survival as its primary endpoint. The registry record does not provide the result needed to answer that primary question.
13. Why This Trial Matters Statistically
Statistically, this trial is notable for a clear primary time-to-event question paired with limited outcome reporting in the registry record. Progression-free survival was defined from randomization to progression or death, with a stated censoring rule and an intention-to-treat population. Those details identify the intended estimand in broad terms, but they do not supply an effect estimate or show its uncertainty.
The study also illustrates why design labels and results must be distinguished. Randomization describes how treatment assignment was intended to occur; open-label describes the absence of masking. Neither feature, alone, conveys the magnitude or precision of the primary comparison. Similarly, a completed status and a stated study objective do not substitute for reported endpoint results.
The registry's enrollment entry and its summary's planned total differ, and the record does not explain the relationship. This is relevant to statistical interpretation because enrollment and the number of participants contributing endpoint information are not necessarily the same, and the record does not report the analysis denominator for progression-free survival. No assumptions should be made about why the figures differ.
The safety entries also demonstrate the distinction between descriptive counts and comparative inference. Counts of participants with events can inform a basic description, but without event definitions, follow-up context, or uncertainty estimates they do not establish the size or precision of a treatment-group contrast. The death field is similarly insufficient to reconstruct the primary time-to-event outcome.
Overall, the record supports a description of the intended design and endpoint but not a statistical conclusion about efficacy. That distinction is important for researchers: an interpretable clinical question is not equivalent to an answer when the primary comparative results are not reported.
14. Limitations
- The posted summary statistics are the only data these results rest on; patient-level data, full protocols and statistical analysis plans are not available.
- Recalculated results are simple, unadjusted calculations from posted summaries. They do not replace the sponsor's prespecified analysis.
The main limitation for interpretation is that the registry record does not report the primary progression-free survival comparison. It provides no group-specific time-to-event estimate, effect estimate, confidence interval, event count, or significance test. As a result, the primary statistical question cannot be answered from the recorded results.
The record lists enrollment as 112, while the study summary describes a planned total of 334. It does not explain the difference, and the number of participants contributing data to the primary endpoint is not reported in the registry record. The completed status does not clarify this discrepancy.
Although progression assessment timing and the censoring definition are described, details about actual follow-up, censoring patterns, missing assessments, and sensitivity analyses are not reported. The statistical model or test, covariate adjustment, allocation procedures, and multiplicity strategy are also not reported in the registry record. These gaps prevent assessment of the analysis assumptions and robustness.
The safety summaries are limited to counts, risk denominators, selected serious-event terms, and death entries. The record does not supply comparative uncertainty estimates, event timing, the definition of the death field, or further context for the listed adverse-event terms. These limitations restrict interpretation of safety contrasts and do not permit causal conclusions.
Finally, the registry summary describes multiple secondary objectives, but their comparative results and the plan for interpreting multiple outcomes are not reported in the registry record. The available information is therefore sufficient to describe the trial question and selected safety observations, but insufficient to reconstruct or assess the primary statistical result.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Phase III Study of Vinflunine Plus Capecitabine Versus Capecitabine Alone in Patients With Advanced Breast Cancer — NCT01953003.
- Registry record last updated 2019-05-02; status last verified 2019-01.
- Results first posted 2019-05-02.
- 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
The record describes a completed, randomized, open-label, parallel-group Phase III study of vinflunine plus capecitabine versus capecitabine alone in advanced breast cancer previously treated with an anthracycline and a taxane. It lists enrollment of 112 and includes a study-summary statement describing a planned total of 334. The study start is listed as 2013-09 and primary completion as 2017-07.
Progression-free survival was the primary endpoint, defined from randomization to documented progression or death from any cause, with censoring for participants without documented progression at their last qualifying assessment or contact. The primary population was described as all randomized patients. The comparative primary result and detailed analysis plan are not reported in the registry record.
Descriptive safety entries include serious adverse events, other adverse events, selected serious-event terms, and deaths by group. The record does not provide a comparative efficacy estimate or uncertainty measure, and it does not explain the enrollment figures' relationship.