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 BIBW 2992 and Letrozole in Hormonoresistant Metastatic Breast Cancer (NCT00708214), a non-randomized phase 2 study. The primary outcome is Percentage of Progression Free Participants After 16 Weeks of Treatment.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT00708214 |
| Phase | Phase 2 |
| Condition | Breast Neoplasms |
| Allocation | Non-Randomized |
| Design model | Not Stated |
| Masking | None (open label) |
| Enrollment | 28 |
| Arms in the primary outcome | n/a |
| Lead sponsor | Boehringer Ingelheim |
| Results posted | Yes |
2. Clinical Question
Population
Patients with hormonoresistant metastatic breast cancer. The primary endpoint population was the treated set: patients dispensed study medication who took at least 1 dose of afatinib.
Intervention
BIBW 2992 in association with letrozole. The registry’s safety groups are identified as afatinib 50 mg, 40 mg, and 30 mg with letrozole.
Comparator
The study was non-randomized. Its registry record does not describe a like-for-like control comparison; the dose groups should not be read as randomized treatment arms.
Primary question
What percentage of treated participants were progression-free after 16 weeks of treatment? The registry record states the endpoint and timeframe but does not report its numerical result or confidence interval.
The study’s stated focus was progression-free status after 16 weeks of BIBW 2992 administered with letrozole. The record also lists secondary outcomes covering objective response, clinical benefit, time to tumour response, response duration, progression-free survival, overall survival, and afatinib exposure measures. Those outcomes describe other aspects of response, follow-up, and drug concentration; their names alone do not establish what was observed.
The registry describes the study as Phase II and non-randomized, with enrollment of 28. Because treatment allocation was not randomized, differences among dose groups cannot be interpreted as if they came from a randomized head-to-head comparison. Participant characteristics, reasons for receiving a particular dose, and any adjustment for such differences are not reported in the registry record.
The primary question is therefore descriptive: the proportion of the treated set meeting the study’s definition of progression-free at the stated assessment time. A numerical estimate and its precision would be needed to assess the observed result. Neither is reported in the registry record.
3. Trial Design
The registry identifies this as a Phase II study sponsored by Boehringer Ingelheim. It lists a start date of 2007-01, primary completion in 2010-02, completed status, and enrollment of 28. The official title describes administration of BIBW 2992 in patients with hormone-refractory metastatic breast cancer; the study title also names letrozole.
Allocation is recorded as non-randomized, and masking as none. These design features matter when interpreting group comparisons. Randomization can help balance measured and unmeasured prognostic characteristics across assigned groups, while masking can reduce some forms of bias in treatment administration or outcome assessment. Neither feature is present according to the registry design fields. Whether other safeguards or adjustments were used is not reported in the registry record.
The record describes BIBW 2992 in association with letrozole and gives arm descriptions for the combination and for letrozole as hormonotherapy. The safety groups are labeled afatinib 50 mg with letrozole, afatinib 40 mg with letrozole, and afatinib 30 mg with letrozole. The record does not provide enough information to treat these dose groups as randomized comparators. It also does not report the allocation process, dose-selection rationale, changes in dose, or participant characteristics by group.
The primary endpoint is the percentage of participants progression-free after 16 weeks of treatment. The endpoint population is the treated set, defined as patients dispensed study medication who took at least 1 dose of afatinib. The registry lists 17 outcome measures and 0 analyses, but gives no numerical primary endpoint estimate, confidence interval, or analysis output. A detailed statistical analysis plan, including how the primary endpoint was estimated, is not reported in the registry record.
Enrollment describes the planned or recorded study size as listed in the registry; it does not by itself say how many participants contributed to the primary endpoint. The number with an evaluable 16-week assessment, any exclusions from the treated set, and the handling of participants without an assessment 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: According to the protocol the starting dose of Afatinib was 50mg/day. This dose was reduced according to the protocol to first 40mg/day and then to 30mg/day due to skin toxicity.
Overall Study
| Stage | Afatinib 50 mg With Letrozole | Afatinib 40 mg With Letrozole | Afatinib 30 mg With Letrozole |
|---|---|---|---|
| STARTED | 7 | 13 | 8 |
| COMPLETED | 0 | 0 | 0 |
| NOT COMPLETED | 7 | 13 | 8 |
Reasons for not completing this period:
| Reason | Afatinib 50 mg With Letrozole | Afatinib 40 mg With Letrozole | Afatinib 30 mg With Letrozole |
|---|---|---|---|
| Other Adverse Event | 3 | 6 | 2 |
| Other | 0 | 1 | 1 |
| Progressive Disease | 4 | 6 | 5 |
Analysis population for the primary outcome, as defined in the registry: Treated set (TS). TS consisted of all patients who were dispensed study medication and have taken at least 1 dose of Afatinib.
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: Treated set (TS). TS consisted of all patients who were dispensed study medication and have taken at least 1 dose of Afatinib.
| Characteristic | Unit | Afatinib 50 mg With Letrozole | Afatinib 40 mg With Letrozole | Afatinib 30 mg With Letrozole | Total |
|---|---|---|---|---|---|
| Participants analysed | 7 | 13 | 8 | 28 | |
| Age, Continuous | years | 63.0 (SD 14.7) | 64.8 (SD 7.2) | 58.5 (SD 9.0) | 62.5 (SD 10.0) |
| Sex: Female, Male: Female | Participants | 7 | 13 | 8 | 28 |
| Sex: Female, Male: Male | Participants | 0 | 0 | 0 | 0 |
6. Primary Endpoint
The registry lists the primary outcome as Percentage of Progression Free Participants After 16 Weeks of Treatment, measured over 16 weeks.
| Element | Registry entry |
|---|---|
| Result type | Number |
| Measure of spread | 95% Confidence Interval |
| Unit | Percentage of participants |
| Endpoint classification | Binary Endpoint |
The primary endpoint is the percentage of participants who were progression-free after 16 weeks of treatment. It is a binary outcome at a specified assessment time: each participant is classified as progression-free or as having progressed under the study definition. The endpoint can be summarized as a proportion, with a confidence interval describing uncertainty around that estimate.
The registry defines progression using several criteria. These include new bone lesions on bone scan or magnetic resonance imaging; progression or new lesions according to RECIST version 1.0; an increase in tumour marker CA 15.3 of more than 20 percent compared with baseline at 2 consecutive examinations; and disease-related skeletal events. It also states that a participant withdrawn because of clinical deterioration amounting to progression according to the investigator was considered to have progressed, even without meeting the other listed criteria.
Using a fixed assessment time makes the endpoint a snapshot of disease status at 16 weeks rather than a direct measure of how long each participant remains progression-free. It may be useful for describing early disease control in the treated set, but its meaning depends on the operational progression criteria and assessment process. Details about assessment schedules, independent review, and missing 16-week assessments are not reported in the registry record.
The registry record does not report the percentage classified as progression-free, the number of participants contributing to that calculation, or a 95% confidence interval. Accordingly, the endpoint’s observed level and precision cannot be assessed from the reported record.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The central interpretive limitation is that the registry record gives the primary endpoint definition but no numerical primary endpoint result. It does not report the percentage of participants progression-free after 16 weeks or the associated 95% confidence interval. Without those values, the size of the observed proportion and its statistical precision cannot be described. The outcome title and study objective are not substitutes for results.
The design also limits what comparisons could establish. Allocation is recorded as non-randomized, with no masking. Dose groups identified in the safety record should therefore not be treated as equivalent groups differing only in dose. Group membership may be associated with participant characteristics or other factors, but those details and any adjustment methods are not reported in the registry record. No causal interpretation of differences between groups is supported by the design information listed.
The progression definition combines imaging findings, a tumour-marker rule, skeletal events, and investigator-assessed clinical deterioration in a specified circumstance. These criteria make the endpoint clinically and operationally broader than a single imaging measure. They also mean that the classification depends on how and when assessments were performed. The assessment procedures and consistency across groups are not reported in the registry record.
The record lists secondary outcomes, including confirmed objective response, clinical benefit, response timing and duration, progression-free survival, overall survival, and afatinib pharmacokinetic measures. It does not provide numerical findings for them in the registry record for this analysis. The outcome list indicates what was planned or recorded as an outcome, not what was observed or whether an outcome favored any group.
General statistical interpretation: a confidence interval expresses uncertainty about an estimated quantity under the assumptions of the analysis. A narrower interval indicates greater precision, while a wider interval indicates less precision. Here, the stated dispersion measure is a 95% confidence interval, but its limits are not reported in the registry record. No significance test, p-value, adjusted estimate, or analysis model is reported either.
Enrollment of 28 gives context for the study scale, but it does not specify the number assessed for the endpoint or the uncertainty around a result. Missing assessments can affect a proportion, particularly if the chance of missing an assessment is related to disease status. The registry’s stated progression rule addresses withdrawal for investigator-assessed clinical deterioration, but it does not fully describe handling of all missing or unevaluable observations.
Overall, the record supports a description of the study question, design, and endpoint definition, but not a quantitative conclusion about the primary outcome. It also does not support a randomized comparison or a claim that the treatment did or did not produce a clinical effect. Any conclusions beyond the design and definitions would require results and methods that are not reported in the registry record.
9. Statistical Methods Explained
The registry identifies a percentage endpoint with a 95% confidence interval as its dispersion measure. It does not report the numerical estimate, interval limits, analysis method, or test results. The concepts below explain how such methods are generally interpreted; they do not describe an analysis confirmed in the registry record.
What does a percentage endpoint represent?
For a binary outcome, each participant is classified into one of two categories for the assessment of interest. The percentage is the share of the analysis population classified as having the outcome. For this study, the outcome is being progression-free after 16 weeks under the registry’s definition. The denominator is important: it should correspond to the participants included in the analysis, not automatically to everyone enrolled. The number contributing to the primary analysis is not reported in the registry record.
A percentage is a summary, not a full account of participant outcomes. It does not show when progression occurred among participants who progressed, how long follow-up continued, or how outcomes varied across clinical subgroups. Those questions require other measures and analyses. The registry lists progression-free survival and other secondary outcomes, but their numerical results are not reported in the record.
What does a confidence interval tell the reader?
General explanation: a confidence interval describes the statistical uncertainty around an estimate under a specified method and its assumptions. It gives a range of values compatible with the observed data under that procedure. It is not a guarantee that the true value lies within the interval, and it does not correct for biases arising from study design, outcome measurement, missing data, or selective reporting.
The primary endpoint specifies a 95% confidence interval, but no estimate or interval endpoints are reported. Consequently, neither the apparent precision nor the range of values compatible with the result can be evaluated. The study’s enrollment figure alone cannot replace the interval, because the number analyzed and the observed distribution are also relevant.
Why does the analysis population matter?
The primary endpoint population is the treated set. The registry defines this as all patients who were dispensed study medication and took at least 1 dose of afatinib. This definition identifies who could contribute under the stated population rule, but the registry record does not state how many met it or how many had an evaluable assessment at 16 weeks.
General explanation: analysis populations answer different questions. A population based on treatment received can describe outcomes among people who started study medication, while other population definitions may preserve assigned groups or require particular follow-up information. In a non-randomized study, population selection can also affect the comparability of groups. The statistical analysis plan and additional population definitions are not reported in the registry record.
How should progression criteria be understood?
The endpoint is not defined by a single criterion. The registry includes new bone lesions, RECIST version 1.0 progression or new lesions, a specified CA 15.3 increase at consecutive examinations, and disease-related skeletal events. It further classifies withdrawal for investigator-assessed clinical deterioration as progression in the stated circumstance. Applying a composite definition means that different kinds of evidence can determine the same endpoint classification.
General explanation: clear operational definitions can support consistent classification, but interpretation still depends on timing, assessment completeness, and the reliability of each component. For example, an imaging-based criterion depends on scan timing and evaluation; a laboratory-based criterion depends on measurement timing and the stated threshold. The registry record does not report detailed assessment procedures, adjudication, or whether outcome assessors were independent.
What can be inferred from non-randomized allocation?
General explanation: without random assignment, groups can differ for reasons that also relate to outcomes. A difference in observed percentages may reflect treatment, participant characteristics, clinical decisions about dose, or other factors. Statistical adjustment can address measured differences under assumptions, but it cannot automatically remove bias from unmeasured factors. The registry records non-randomized allocation and no masking; it does not report a comparative model or adjustment strategy.
The safety record identifies dose groups with letrozole, but their presence does not establish a randomized dose comparison. The sample-size assumptions describe an illustration based on an observed effect, with a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. The stated effect to detect is a fraction of the observed effect. These are planning assumptions, not proof of the study’s original design or observed power. No numerical planning output or observed primary effect is reported in the registry record.
Why can over-dispersion matter in general?
General explanation: some statistical models assume that the variability in observed outcomes follows a particular pattern. Over-dispersion means the data vary more than that model expects. If it is ignored, uncertainty can be understated and tests can appear more decisive than warranted. The registry record does not identify a model for the primary endpoint, report a dispersion assessment, or indicate that over-dispersion was evaluated. This concept is therefore relevant as general statistical context, not as a reported feature of this study’s analysis.
The registry lists 17 outcome measures and 0 analyses. It does not report a statistical analysis plan, interim analyses, sample-size justification, hypothesis-testing strategy, or multiplicity adjustment. These omissions prevent a fuller assessment of how the primary estimate and its uncertainty were intended to be calculated.
10. Exact Estimates for Each Arm
No two-arm comparison is shown for this trial, but each arm's result can still be summarized with exact interval estimates computed from the posted counts. The Clopper-Pearson interval is exact and conservative; the Wilson interval is a common closer-to-nominal alternative; the Bayesian credible interval uses a uniform Beta(1, 1) prior. For small groups the three can differ noticeably.
| Arm | Participants | Events | Observed % | Clopper-Pearson 95% CI | Wilson 95% CI | Bayesian 95% credible interval |
|---|---|---|---|---|---|---|
| Afatinib 50 mg With Letrozole | 7 | 2 | 28.6% | 3.7% to 71.0% | 8.2% to 64.1% | 8.5% to 65.1% |
| Afatinib 40 mg With Letrozole | 13 | 0 | 0.0% | 0.0% to 24.7% | 0.0% to 22.8% | 0.2% to 23.2% |
| Afatinib 30 mg With Letrozole | 8 | 2 | 25.0% | 3.2% to 65.1% | 7.1% to 59.1% | 7.5% to 60.0% |
R code and output
arm <- c("Afatinib 50 mg With Letrozole", "Afatinib 40 mg With Letrozole", "Afatinib 30 mg With Letrozole")
n <- c(7, 13, 8)
events <- c(2, 0, 2)
for (i in seq_along(n)) {
ci <- binom.test(events[i], n[i])$conf.int # Clopper-Pearson exact interval
cr <- qbeta(c(0.025, 0.975), 1 + events[i], 1 + n[i] - events[i]) # Bayesian, uniform Beta(1,1) prior
wi <- (function(x, n) { p <- x / n; z <- qnorm(0.975); d <- 1 + z^2 / n
c((p + z^2 / (2 * n) - z * sqrt(p * (1 - p) / n + z^2 / (4 * n^2))) / d, (p + z^2 / (2 * n) + z * sqrt(p * (1 - p) / n + z^2 / (4 * n^2))) / d) })(events[i], n[i])
cat(sprintf("ARM|%s|%d|%d|%.1f|%.1f|%.1f|%.1f|%.1f|%.1f|%.1f\n", arm[i], n[i], events[i], 100 * events[i] / n[i],
100 * ci[1], 100 * ci[2], 100 * wi[1], 100 * wi[2], 100 * cr[1], 100 * cr[2]))
}
ARM Afatinib 50 mg With Letrozole 7 2 28.6 3.7 71.0 8.2 64.1 8.5 65.1
ARM Afatinib 40 mg With Letrozole 13 0 0.0 0.0 24.7 0.0 22.8 0.2 23.2
ARM Afatinib 30 mg With Letrozole 8 2 25.0 3.2 65.1 7.1 59.1 7.5 60.011. Multiplicity, Missing Data and Analysis Populations
The registry lists 17 outcome measures, spanning the primary progression-free percentage and secondary outcomes that include response, survival, and pharmacokinetic measures. It records 0 analyses and does not report a statistical analysis plan, hypothesis-testing hierarchy, or adjustment for multiple comparisons. The record therefore does not establish which outcomes were formally tested, how they were prioritized, or how multiplicity was addressed.
General explanation: when many outcomes or comparisons are examined, the chance of obtaining at least one apparently unusual result can increase if each is tested separately. Prespecified priorities and multiplicity procedures can help readers interpret a collection of tests. Because no test results or plan are reported, it is not possible to assess whether multiplicity influenced interpretation in this study.
Missing-data handling is also not reported in detail. The endpoint definition states that a participant withdrawn because of investigator-assessed clinical deterioration amounting to progression was considered to have progressed. That rule addresses a specified situation, but does not explain how other missing 16-week assessments, incomplete imaging, or participants with unknown progression status were handled. The number of participants with missing or unevaluable endpoint data is not reported in the registry record.
The stated treated set includes patients dispensed study medication who took at least 1 dose of afatinib. The record does not report the number analyzed under this definition, additional analysis populations, or whether participants were excluded from the primary analysis. Those details matter because both the numerator and denominator of a percentage depend on the analysis rules and available observations.
Interim analyses, stopping rules, and sample-size justification are not reported in the registry record. Their absence from the record should not be interpreted as evidence that such procedures were or were not used; it means they cannot be evaluated from the documented information.
12. 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 |
|---|---|---|---|
| Afatinib 50 mg With Letrozole | 1 | 7 | 14.3% |
| Afatinib 40 mg With Letrozole | 3 | 13 | 23.1% |
| Afatinib 30 mg With Letrozole | 5 | 8 | 62.5% |
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 |
|---|---|
| Afatinib 50 mg With Letrozole | 7 of 7 |
| Afatinib 40 mg With Letrozole | 13 of 13 |
| Afatinib 30 mg With Letrozole | 8 of 8 |
Most frequent serious adverse event terms
| Event term | Organ system | Afatinib 50 mg With Letrozole | Afatinib 40 mg With Letrozole | Afatinib 30 mg With Letrozole |
|---|---|---|---|---|
| Vomiting | Gastrointestinal disorders | 0 of 7 | 1 of 13 | 1 of 8 |
| Dehydration | Metabolism and nutrition disorders | 0 of 7 | 1 of 13 | 1 of 8 |
| Disseminated intravascular coagulation | Blood and lymphatic system disorders | 0 of 7 | 1 of 13 | 0 of 8 |
| Diarrhoea | Gastrointestinal disorders | 0 of 7 | 1 of 13 | 0 of 8 |
| Nausea | Gastrointestinal disorders | 0 of 7 | 0 of 13 | 1 of 8 |
| Asthenia | General disorders | 0 of 7 | 0 of 13 | 1 of 8 |
| Mucosal inflammation | General disorders | 0 of 7 | 1 of 13 | 0 of 8 |
| Obstruction | General disorders | 0 of 7 | 1 of 13 | 0 of 8 |
| Oedema peripheral | General disorders | 0 of 7 | 1 of 13 | 0 of 8 |
| Arthritis bacterial | Infections and infestations | 0 of 7 | 1 of 13 | 0 of 8 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Afatinib 50 mg With Letrozole | Afatinib 40 mg With Letrozole | Afatinib 30 mg With Letrozole |
|---|---|---|---|---|
| Diarrhoea | Gastrointestinal disorders | 7 of 7 | 12 of 13 | 7 of 8 |
| Asthenia | General disorders | 4 of 7 | 8 of 13 | 4 of 8 |
| Rash | Skin and subcutaneous tissue disorders | 5 of 7 | 5 of 13 | 6 of 8 |
| Nausea | Gastrointestinal disorders | 4 of 7 | 4 of 13 | 3 of 8 |
| Epistaxis | Respiratory, thoracic and mediastinal disorders | 3 of 7 | 5 of 13 | 3 of 8 |
| Mucosal inflammation | General disorders | 5 of 7 | 3 of 13 | 2 of 8 |
| Acne | Skin and subcutaneous tissue disorders | 5 of 7 | 3 of 13 | 1 of 8 |
| Decreased appetite | Metabolism and nutrition disorders | 1 of 7 | 4 of 13 | 2 of 8 |
| Constipation | Gastrointestinal disorders | 3 of 7 | 1 of 13 | 3 of 8 |
| Conjunctivitis | Eye disorders | 2 of 7 | 2 of 13 | 2 of 8 |
Serious events with the highest arm-level rate: erysipelas (14.3%), sinusitis (14.3%), melanocytic naevus (14.3%), nausea (12.5%), vomiting (12.5%).
The safety record separates serious adverse events from other adverse events and lists three dose groups with letrozole. In the afatinib 50 mg group, 1 participant is listed as affected by a serious adverse event among 7 at risk; 7 are listed as affected by other adverse events among 7 at risk. In the afatinib 40 mg group, the corresponding entries are 3 among 13 for serious adverse events and 13 among 13 for other adverse events. In the afatinib 30 mg group, they are 5 among 8 and 8 among 8, respectively.
These are descriptive counts within groups, not randomized comparative estimates. The non-randomized design means the groups should not be treated as directly comparable for estimating a dose effect. The record does not report adjustment for differences among groups, exposure duration, or a statistical comparison of safety outcomes.
The listed serious adverse event terms include erysipelas, sinusitis, and melanocytic naevus at 14.3% each, and nausea, vomiting, and asthenia at 12.5% each. The record does not specify in the registry record which dose group each term belongs to, so these percentages should not be assigned to a particular group.
Deaths are recorded as null for each group. This is not a reported count of zero; death information is not reported in the registry record. Counts and percentages describe events recorded during the study and do not by themselves establish that treatment caused an event or establish comparative risk.
13. What the Result Does, and Does Not, Mean
The record establishes that the study asked about the percentage of treated participants who were progression-free after 16 weeks of BIBW 2992 with letrozole. It also provides a detailed operational definition of progression and identifies the treated set as the primary endpoint population. These details clarify the intended question, but they do not reveal the answer.
The registry does not report the primary endpoint percentage, its 95% confidence interval, or the number of participants contributing to the estimate. It also does not give numerical findings for the listed secondary outcomes in the record. As a result, the magnitude and precision of the primary outcome cannot be described, and the secondary outcome names cannot be interpreted as evidence of a particular result.
The study is recorded as non-randomized and unmasked. This permits descriptive reporting of outcomes in the study population, but limits causal interpretation and direct comparisons between groups. The dose groups in the safety record are not a substitute for a randomized control group. Differences among them could reflect factors other than dose, and the registry does not report participant-level characteristics or adjustment methods that would clarify this issue.
General explanation: a study can be informative about feasibility, outcome definitions, and the range of observations collected even when its design does not support a strong causal comparison. However, a treatment effect cannot be inferred from the endpoint definition or enrollment alone. Statistical significance, clinical importance, and precision are separate questions; the record does not report the results needed to assess them for the primary endpoint.
The safety counts are descriptive and should be read with the group labels and denominators in mind. They do not establish causation, and the null entries for deaths do not establish that no deaths occurred. The registry record does not report death counts.
In short, the record describes a Phase II, non-randomized study and its 16-week progression-free endpoint, but it does not provide a numerical primary result. It therefore supports no conclusion that the treatment did or did not produce a benefit or harm.
14. Why This Trial Matters Statistically
This study is statistically relevant because its primary endpoint illustrates the distinction between a clearly stated estimand and a reported estimate. The registry identifies a population, a progression-free outcome, a 16-week assessment time, and a 95% confidence interval as the intended measure of uncertainty. Yet the numerical result and interval are not reported in the registry record. Without them, a reader can understand what was to be measured but cannot assess the observed level or its precision.
The progression definition also shows how endpoint construction shapes interpretation. Imaging findings, a tumour-marker rule, skeletal events, and investigator-assessed deterioration contribute to classification. A composite definition can capture multiple forms of progression, but the components and assessment process need to be understood when interpreting a resulting percentage. The registry gives the criteria but does not report detailed assessment or adjudication procedures.
The non-randomized design is another important statistical feature. Dose-group outcomes may be useful descriptively, but the groups are not automatically exchangeable. A comparative estimate would need to account for the design and relevant differences, and the registry record does not report such an analysis. Treating dose groups as if they were randomized would overstate what the design can establish.
The record’s outcome list spans response, survival, and pharmacokinetic measures, while documenting 0 analyses. This makes transparent reporting of outcome-specific results and analysis methods especially important: readers need to distinguish outcomes that were listed from outcomes that were analyzed and reported. Details about multiplicity, missing data, and the analysis plan are not reported in the registry record.
These features make the trial a useful example of why endpoint definitions, analysis populations, design, and numerical reporting must be read together. None of those elements alone can replace the missing primary estimate and its uncertainty.
15. 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 principal trial-specific limitation in the registry record is the absence of numerical results for the primary endpoint. Although the endpoint is defined as the percentage progression-free after 16 weeks and a 95% confidence interval is specified, neither the percentage nor interval limits are reported. The denominator and number of missing or unevaluable assessments are also not reported.
Allocation is non-randomized and masking is listed as none. The record does not describe the allocation process, reasons for dose selection, baseline characteristics by group, or comparative adjustment. Consequently, apparent differences among dose groups cannot be interpreted as unbiased dose effects from the information recorded.
The endpoint uses several progression criteria, including imaging, tumour marker, skeletal events, and investigator-assessed clinical deterioration in a stated circumstance. Details of assessment timing, review procedures, and consistency of measurement are not reported in the registry record. The contribution of each criterion to endpoint classification is also not reported.
The record lists 17 outcome measures and 0 analyses, but does not report a statistical analysis plan, multiplicity approach, interim analyses, sample-size justification, or hypothesis-testing strategy. It also does not explain handling of missing endpoint data beyond the specified withdrawal rule. These omissions limit assessment of analysis choices and the risk of selective interpretation.
Safety reporting has its own limits: deaths are recorded as null, not as a numerical count, and the listed serious adverse event percentages are not linked to a specific dose group in the information available. The safety counts are descriptive and arise from a non-randomized study. Exposure duration and adjusted safety comparisons are not reported in the registry record.
16. Related Tutorials
17. Related Statistical Calculators
18. Sources
- ClinicalTrials.gov: BIBW 2992 and Letrozole in Hormonoresistant Metastatic Breast Cancer — NCT00708214.
- Registry record last updated 2013-12-30; status last verified 2013-10.
- Results first posted 2013-11-19.
- 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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Use this trial's endpoint as a starting point for deeper study of effect measures, confidence intervals, and sample-size planning.
19. Record Summary
The registry describes a completed, non-randomized Phase II study sponsored by Boehringer Ingelheim, with enrollment of 28. The study concerns BIBW 2992 with letrozole in hormonoresistant metastatic breast cancer. The listed start is 2007-01 and primary completion is 2010-02.
The primary endpoint is the percentage of the treated set progression-free after 16 weeks. The registry defines progression using imaging, RECIST version 1.0, a CA 15.3 threshold at consecutive examinations, skeletal events, and a specified investigator-assessed deterioration rule. The treated set consists of patients dispensed study medication who took at least 1 dose of afatinib.
The record lists 17 outcome measures and 0 analyses. It does not report the primary endpoint estimate, its 95% confidence interval, or detailed analysis and missing-data methods. Allocation is non-randomized and masking is none, so the dose groups should not be treated as randomized comparators. Safety counts are reported by dose group, while death entries are null rather than numerical counts.