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 An Observational Study of Xeloda (Capecitabine) in Participants With Metastatic or Advanced Breast Cancer (NCT01725386), a registered phase not stated study. The primary outcome is Percent of Participants With Capecitabine as a First Line, Second Line, or Third Line Therapy.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT01725386 |
| Phase | Phase not stated |
| Condition | Breast Cancer |
| Allocation | Not Stated |
| Design model | Not Stated |
| Masking | Not Stated |
| Enrollment | 274 |
| Arms in the primary outcome | n/a |
| Lead sponsor | Hoffmann-La Roche |
| Results posted | Yes |
2. Clinical Question
Population
Participants with metastatic or advanced breast cancer who received at least one dose of capecitabine and had data for at least one follow-up variable were eligible for the primary analysis. The registry record reports enrollment of 274 participants, but does not report the number included in that analysis.
Intervention
Capecitabine, also called Xeloda, was used in routine clinical practice. The record describes both monotherapy and combination therapy, according to prescribing information and normal clinical practice.
Comparator
There was no stated randomized comparator. Monotherapy and combination therapy are descriptive treatment groups, not like-for-like control groups. Allocation is not stated, and treatment selection followed clinical practice.
Primary question
The study aimed to document whether capecitabine was used as first-line, second-line or third-line therapy, and whether it was given alone or as part of combination therapy. The registry record does not report the percentages for those treatment-line categories.
The question is about patterns of use rather than a randomized estimate of comparative efficacy. The study also recorded baseline characteristics, mean survival time and adverse events among its secondary outcomes. The primary outcome description says treatment choice was summarized according to line of therapy; it does not state that the study tested whether one treatment approach was better than another.
3. Trial Design
This was an observational study of capecitabine use in participants with metastatic or advanced breast cancer. The sponsor was Hoffmann-La Roche. The registry record lists the study as completed, with a start date of 2011-03 and primary completion in 2015-02. Enrollment was 274. Participants were to be followed for up to 24 months, while the primary outcome timeframe is recorded as up to approximately 4 years.
The study described two treatment settings: capecitabine monotherapy and capecitabine as part of combination therapy. Both were used according to prescribing information and normal clinical practice. The registry record does not state how treatment assignment or selection was made beyond that description. It does not identify a randomized allocation process, and the listed groups should not be interpreted as equivalent groups created by randomization.
The primary analysis population consisted of participants who received at least one dose of study medication and had data for at least one follow-up variable. The record does not report how many participants met that definition. It lists six outcome measures and one analysis, but does not provide the primary endpoint’s numerical result in the registry information used for this account.
Listed secondary outcomes include baseline medical history, histopathology grade, mean survival time and adverse events. The record also gives counts of participants affected by serious and other adverse events in each treatment group and names selected serious event terms. Details of how these outcomes were analyzed, including any adjustment for differences between treatment groups, 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.
Before assignment: 274 participants were enrolled in the study; of these, 23 participants from 3 centers were excluded from the analysis due to study termination at those 3 centers. The remaining 251 participants were eligible for analysis.
Overall Study
| Stage | Monotherapy | Combination Therapy |
|---|---|---|
| STARTED | 188 | 63 |
| COMPLETED | 13 | 17 |
| NOT COMPLETED | 175 | 46 |
Reasons for not completing this period:
| Reason | Monotherapy | Combination Therapy |
|---|---|---|
| Death | 84 | 40 |
| Lost to Follow-up | 81 | 6 |
| Withdrawal by Subject | 10 | 0 |
Analysis population for the primary outcome, as defined in the registry: Participants eligible for analysis (received at least one dose of study medication and for whom data for at least one follow-up variable were available).
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.
Population: Participants eligible for analysis (received at least one dose of study medication and for whom data for at least one follow-up variable were available).
| Characteristic | Unit | Monotherapy | Combination Therapy | Total |
|---|---|---|---|---|
| Participants analysed | 188 | 63 | 251 | |
| Age, Continuous | years | 47.00 (SD 12.35) | 45.00 (SD 15.19) | 47.00 (SD 12.11) |
| Sex: Female, Male: Female | Participants | 188 | 63 | 251 |
| Sex: Female, Male: Male | Participants | 0 | 0 | 0 |
6. Primary Endpoint
The registry lists the primary outcome as Percent of Participants With Capecitabine as a First Line, Second Line, or Third Line Therapy, measured over Up to approximately 4 years.
| Element | Registry entry |
|---|---|
| Result type | Number |
| Measure of spread | not applicable |
| Unit | percentage of participants |
| Endpoint classification | Binary Endpoint |
The primary endpoint is the percentage of participants receiving capecitabine as first-line, second-line or third-line therapy. It describes where capecitabine entered the sequence of treatment for metastatic breast cancer. The endpoint also relates treatment line to the choice between capecitabine monotherapy and combination therapy, as described in the registry record.
This measure is useful for documenting routine practice: it can describe how often the medicine was used at different points in treatment. It is not, by itself, a measure of tumor response, survival benefit or comparative effectiveness. A treatment-line percentage characterizes use; it does not establish why a clinician selected that line or whether the selection changed an outcome.
The denominator is the primary analysis population: participants who received at least one dose and had data for at least one follow-up variable. The registry record does not report the number analyzed or the percentages in the line-of-therapy categories. It therefore does not allow the distribution to be quantified or its precision to be assessed. The timeframe is recorded as up to approximately 4 years.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The registry record describes a completed observational study with enrollment of 274 participants. Its stated primary purpose was to document capecitabine use by treatment line and by use as monotherapy or combination therapy. However, it does not report the numerical primary endpoint result. The available record therefore does not establish what proportion received capecitabine as first-line, second-line or third-line therapy, nor how those choices were distributed between the two treatment settings.
The record identifies 188 participants at risk for the serious adverse event summary in the monotherapy group, of whom 85 were affected. For combination therapy, 63 were at risk and 42 were affected. For other adverse events, the corresponding counts are 188 at risk and 73 affected for monotherapy, and 63 at risk and 42 affected for combination therapy. These are descriptive group summaries. Because treatment was not described as randomized and allocation is not stated, differences between the groups cannot be attributed to treatment setting from these figures alone.
Selected serious event terms are listed with percentages: Cardiopulmonary Arrest, 42.9%; Respiratory Distress/Failure, 11.1%; Ascites, 6.3%; Dyspnea, 6.3%; Diarrhoea, 4.8%; and Melena, 4.8%. The registry record does not identify the denominator for these term percentages or explain whether a participant could contribute to more than one term. They should therefore be read as reported event summaries, not as directly comparable risks for the treatment groups.
General statistical interpretation: a point estimate describes the observed data, while a confidence interval, if reported, would describe uncertainty around that estimate under the analysis assumptions. The registry record does not report a confidence interval for the primary endpoint. Without the endpoint result and its uncertainty, the precision of the treatment-line description cannot be assessed. The record also does not report a comparative treatment effect or a statistical test for monotherapy versus combination therapy.
The evidence recorded is consequently most informative as a description of study design, analysis eligibility and selected adverse event counts. It does not support a causal comparison of treatment approaches, and it leaves the primary treatment-line distribution unquantified.
9. Statistical Methods Explained
The primary measure is a percentage, a way to express how many members of a defined analysis population fall into a category. Its interpretation depends on the numerator, the denominator and the rules used to assign participants to categories. Here, the intended categories are use of capecitabine as first-line, second-line or third-line therapy, with the treatment setting described as monotherapy or combination therapy. The registry record does not report the category counts or percentages, so those quantities cannot be evaluated.
What does an observational comparison mean?
General statistical explanation: in an observational study, treatment groups arise through clinical practice rather than a stated randomized allocation. Participants receiving different approaches can differ in ways that also relate to outcomes. This means a difference between group summaries is not automatically an effect caused by treatment. The record describes capecitabine use according to prescribing information and normal clinical practice, and says allocation is not stated. It explicitly cautions that the arms are not a like-for-like control comparison.
For that reason, the monotherapy and combination therapy counts are best interpreted descriptively. The registry record does not report adjustment for differences between participants, a matching procedure or another method intended to make the groups comparable. It also does not report a formal hypothesis test comparing these groups. The numerical summaries alone cannot resolve confounding or establish why one treatment setting was selected.
How should a percentage be read?
General statistical explanation: a percentage is meaningful only with a clear denominator. A percentage among all enrolled participants can differ from a percentage among participants who received treatment, completed follow-up or had a particular assessment. The primary analysis population is defined as participants who received at least one dose and had data for at least one follow-up variable. The number meeting that definition is not reported in the registry record. The denominator used for the serious adverse event term percentages is also not reported, so those percentages should not be treated as group-specific participant risks.
A confidence interval, when reported, gives a range of values compatible with the observed data under the statistical model and its assumptions. It conveys precision, not certainty that a particular value is true. No confidence interval for the primary endpoint is reported in the registry record. Thus, even if the intended endpoint is clear, its precision cannot be judged from the information recorded.
What can adverse event counts establish?
The serious and other adverse event summaries provide counts of participants at risk and affected in each treatment group. They are useful as descriptions of recorded events, but interpretation depends on how events were defined, collected and attributed, as well as the observation period. The registry record gives a follow-up plan of up to 24 months, but does not describe event ascertainment procedures or provide exposure-adjusted event rates. It also does not report deaths in these group summaries. Those details should not be inferred from the listed counts.
The selected serious event terms are accompanied by percentages, but their denominator and counting rules are not stated. General statistical explanation: event-term percentages can describe the composition of reported events rather than the probability that a participant experiences an event. The distinction matters when participants may experience multiple events or when the denominator is a subset of reported events. Because the registry record does not clarify these points, the percentages should be read narrowly as reported term summaries.
What is not available about the analysis?
The record lists six outcome measures and one analysis. It does not describe the statistical model, handling of missing values, confidence interval method, hypothesis tests or adjustment for multiple outcomes. No recalculated estimate is reported in the registry record. The sample-size assumptions describe a planning illustration based on an observed effect, with a two-sided significance level of 0.05, equal allocation and a normal approximation; such an illustration is not an observed treatment effect or observed power. No numerical planning result is reported in the information used for this account.
These gaps limit what can be concluded about precision and group comparisons. The primary endpoint remains a useful description of intended treatment-use patterns, but without its observed values or fuller analysis details, it cannot quantify those patterns or support an inference about comparative outcomes.
10. Multiplicity, Missing Data and Analysis Populations
The registry record lists six outcome measures and one analysis. It names secondary outcomes concerning relevant medical history, histopathology grade, mean survival time and adverse events, in addition to the primary treatment-line measure. The record does not report how many statistical tests were performed for these outcomes, whether outcomes were analyzed in multiple subgroups, or whether any adjustment for multiple comparisons was used. A multiplicity procedure is not reported in the registry record.
General statistical explanation: when several outcomes or comparisons are examined, the chance of at least one apparently unusual result can increase. Adjustment methods can address this issue, but the appropriate interpretation depends on the prespecified analysis plan and the number and relationship of tests. Because those details are not reported, it is not possible to determine whether multiplicity was considered or how it might affect any inferential result.
The primary analysis population required at least one dose and data for at least one follow-up variable. The number of participants meeting that criterion is not reported in the registry record. The record does not describe how missing outcome data were handled, whether participants with incomplete follow-up were excluded from particular analyses, or whether any imputation was used. It also does not report the completeness of data for the secondary outcomes.
Consequently, the impact of missing data and the precision of the primary endpoint cannot be evaluated from the recorded information. The enrollment total of 274 should not be assumed to be the denominator for every outcome: the primary population has a separate eligibility definition, and outcome-specific denominators are not reported.
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 |
|---|---|---|---|
| Monotherapy | 85 | 188 | 45.2% |
| Combination Therapy | 42 | 63 | 66.7% |
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 |
|---|---|
| Monotherapy | 73 of 188 |
| Combination Therapy | 42 of 63 |
Most frequent serious adverse event terms
| Event term | Organ system | Monotherapy | Combination Therapy |
|---|---|---|---|
| Cardiopulmonary Arrest | Cardiac disorders | 66 of 188 | 27 of 63 |
| Respiratory Distress/Failure | Respiratory, thoracic and mediastinal disorders | 10 of 188 | 7 of 63 |
| Shortness of breath | Respiratory, thoracic and mediastinal disorders | 5 of 188 | 3 of 63 |
| Ascites | Gastrointestinal disorders | 3 of 188 | 4 of 63 |
| Dyspnea | Respiratory, thoracic and mediastinal disorders | 3 of 188 | 4 of 63 |
| Jaundice | Investigations | 4 of 188 | 2 of 63 |
| Haemoptysis | Respiratory, thoracic and mediastinal disorders | 2 of 188 | 3 of 63 |
| Diarrhoea | Gastrointestinal disorders | 1 of 188 | 3 of 63 |
| Melena | Gastrointestinal disorders | 1 of 188 | 3 of 63 |
| Generalized Fits | Nervous system disorders | 2 of 188 | 2 of 63 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Monotherapy | Combination Therapy |
|---|---|---|---|
| Hand-and-Foot Syndrome | Skin and subcutaneous tissue disorders | 20 of 188 | 17 of 63 |
| Vomiting | Gastrointestinal disorders | 16 of 188 | 16 of 63 |
| Diarrhea | Gastrointestinal disorders | 13 of 188 | 12 of 63 |
| Nausea | Gastrointestinal disorders | 8 of 188 | 13 of 63 |
| Fatigue | General disorders | 13 of 188 | 6 of 63 |
| Stomatitis | Gastrointestinal disorders | 4 of 188 | 13 of 63 |
| Pyrexia | General disorders | 5 of 188 | 6 of 63 |
| Bone Pain | Musculoskeletal and connective tissue disorders | 11 of 188 | 0 of 63 |
| Myalgia | Musculoskeletal and connective tissue disorders | 2 of 188 | 6 of 63 |
| Alopecia | Skin and subcutaneous tissue disorders | 0 of 188 | 8 of 63 |
Serious events with the highest arm-level rate: cardiopulmonary arrest (42.9%), respiratory distress/failure (11.1%), ascites (6.3%), dyspnea (6.3%), diarrhoea (4.8%).
The serious adverse event summary lists 188 participants at risk and 85 affected in the monotherapy group, and 63 at risk and 42 affected in the combination therapy group. For other adverse events, the corresponding figures are 188 at risk and 73 affected with monotherapy, and 63 at risk and 42 affected with combination therapy. These figures describe the recorded groups; they do not establish that treatment setting caused any difference.
The listed serious event terms and percentages are Cardiopulmonary Arrest, 42.9%; Respiratory Distress/Failure, 11.1%; Ascites, 6.3%; Dyspnea, 6.3%; Diarrhoea, 4.8%; and Melena, 4.8%. The denominator for these percentages is not reported in the registry record, so they cannot be interpreted as percentages of all participants in either treatment group. The record does not explain whether a participant could be counted under multiple terms.
Deaths are not reported in the registry record. Event definitions, collection procedures and exposure-adjusted rates are also not reported, limiting comparisons. These safety figures are descriptive summaries, not a randomized estimate of comparative risk.
12. What the Result Does, and Does Not, Mean
The study’s primary question concerns routine use: whether capecitabine was selected as first-line, second-line or third-line therapy, and whether it was used alone or in combination. The registry record states this objective but does not report the primary endpoint values. It is therefore not possible to state the observed treatment-line distribution or how precisely it was estimated.
The record does report adverse event counts for the two treatment groups and selected serious event terms with percentages. These provide descriptive information about events recorded in the study. They do not, on their own, quantify a causal difference between monotherapy and combination therapy. The study is observational, allocation is not stated, and the groups are explicitly not a like-for-like control comparison.
General statistical explanation: association and causation are different claims. A group difference can reflect treatment, participant characteristics, clinical decisions or other factors. A design and analysis that address those alternatives are needed before a causal interpretation is justified. Such adjustment methods are not described in the registry record.
The enrollment total is 274, but the primary endpoint’s analysis population has a narrower eligibility definition. Its size is not reported, and the registry record does not explain missing-data handling. The denominator and counting rules for the serious event term percentages are also not reported. These omissions make it difficult to assess the precision and scope of the descriptive findings.
The study can therefore be understood as an effort to document clinical use and safety in routine practice. The recorded information does not establish comparative efficacy, a treatment effect on survival, or the primary treatment-line percentages. Those conclusions would require results and methodological details not reported in the registry record.
13. Why This Trial Matters Statistically
Observational studies address a different statistical question from randomized trials. They can describe how a treatment is used in routine practice and what events are recorded among participants receiving it. That role is relevant to this study, whose stated purpose was to document capecitabine use in metastatic or advanced breast cancer, including the treatment line and whether it was used alone or in combination.
The registry record also illustrates why a clearly named endpoint is not enough to assess a result. The primary endpoint is identifiable and its analysis population is defined, but the endpoint percentages and analysis-population size are not reported. Without those values, readers cannot assess the distribution of treatment lines or the precision of the estimate.
The two treatment settings are not randomized comparison arms. Describing them side by side can be informative, but the groups may differ because treatment followed routine clinical practice. The record states that allocation is not given and cautions against treating the arms as like-for-like controls. This is an important boundary on interpretation, especially for adverse event counts.
Finally, safety summaries need denominators and clear event definitions to support meaningful comparison. The record provides counts for participants at risk and affected, as well as selected serious event terms, but does not report the denominator for those term percentages or the event-collection details. Recognizing what is and is not specified helps keep descriptive evidence separate from causal claims.
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 endpoint’s numerical result is not reported in the registry record. Although the outcome is defined as the percentage of participants receiving capecitabine as first-line, second-line or third-line therapy, the category counts, percentages and analysis-population size are not available. This prevents assessment of the main stated objective and its precision.
The record reports enrollment of 274, but eligibility for the primary analysis required receipt of at least one dose and data for at least one follow-up variable. The relationship between enrollment and the analysis population is not reported. Missing-data methods, outcome-specific denominators and completeness of follow-up are also not reported in the registry record.
The treatment groups are observational, and allocation is not stated. The record cautions that they are not like-for-like controls. It does not report adjustment for participant differences or a formal comparative analysis. Accordingly, differences in adverse event counts cannot be attributed to the treatment setting on the basis of these summaries.
The denominator for the selected serious event term percentages is not stated, and the registry record does not explain event counting or whether participants could contribute to multiple terms. Deaths are not reported in the registry record. Event definitions, collection procedures and exposure-adjusted rates are not described.
The record lists six outcome measures and one analysis, but does not report multiplicity handling or detailed statistical methods. It also does not report the primary endpoint’s confidence interval. These limitations leave the main descriptive result unquantified and constrain interpretation of the safety summaries.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: An Observational Study of Xeloda (Capecitabine) in Participants With Metastatic or Advanced Breast Cancer — NCT01725386.
- Registry record last updated 2016-09-28; status last verified 2016-08.
- Results first posted 2016-08-12.
- 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
This completed observational study examined routine capecitabine use in metastatic or advanced breast cancer. Hoffmann-La Roche is listed as sponsor. The registry record gives a start date of 2011-03, primary completion in 2015-02 and enrollment of 274. Participants were to be followed for up to 24 months.
The primary outcome concerns capecitabine use as first-line, second-line or third-line therapy, with monotherapy and combination therapy described. Its numerical result and analysis-population size are not reported in the registry record. The record lists six outcome measures and one analysis.
Adverse event counts are reported for the two treatment groups, alongside selected serious event terms and percentages. Since the study is observational and allocation is not stated, these summaries do not establish a causal comparison between treatment settings. The record does not report the denominator for the serious event term percentages, deaths, detailed missing-data methods or a primary endpoint confidence interval.