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 Lapatinib and Tamoxifen in Treating Patients With Locally Advanced or Metastatic Breast Cancer That Did Not Respond to Previous Tamoxifen (NCT00118157), a na phase 2 study. The primary outcome is Tumor Response Rate (Complete and Partial) Assessed by Response Evaluation Criteria in Solid Tumors (RECIST).
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT00118157 |
| Phase | Phase 2 |
| Condition | Estrogen Receptor Positive, Male Breast Carcinoma, Progesterone Receptor Positive |
| Allocation | Not applicable (single group) |
| Design model | Single Group |
| Masking | None (open label) |
| Enrollment | 19 |
| Arms in the primary outcome | n/a |
| Lead sponsor | National Cancer Institute (NCI) |
| Results posted | Yes |
2. Clinical Question
Population
Patients with locally advanced or metastatic breast cancer that had not responded to previous tamoxifen were the intended population. The registry lists estrogen receptor positive and progesterone receptor positive disease, male breast carcinoma, recurrent breast carcinoma, and stage IIIB, stage IIIC, and stage IV breast cancer among the conditions. Enrollment was 19.
Intervention
Patients received lapatinib ditosylate by mouth daily together with tamoxifen citrate by mouth daily. Courses were planned to repeat every 28 days while there was no disease progression or unacceptable toxicity. Laboratory biomarker analysis was also listed as an intervention.
Comparator
There was no separate comparator group. The registry describes a single-group study, with allocation recorded as not applicable and no masking. Consequently, the study does not provide a randomized, like-for-like comparison against tamoxifen alone or another treatment.
Primary question
The primary endpoint was the number of participants with a complete or partial tumor response assessed using RECIST. The registry lists a 4-week timeframe and a 95% confidence interval for this participant-count outcome. It does not report the response count, response rate, confidence interval, or statistical analysis result in the registry record.
The clinical question is therefore whether tumor responses were recorded among participants treated with the combination in this single group, and how precisely any response estimate could be described. The record identifies the population and treatment but does not supply the outcome result needed to characterize the observed response. Even if a response estimate were available, without a concurrent control group it would describe outcomes during combination treatment rather than establish what would have happened under a different treatment.
3. Trial Design
This was a phase II study with a single treatment group. The registry records enrollment of 19 participants, allocation as not applicable, and masking as none. These features mean that the study was not a masked randomized comparison: all participants in the treatment group received lapatinib ditosylate and tamoxifen citrate. The registry lists the sponsor as the National Cancer Institute (NCI).
The treatment description specifies both drugs taken by mouth daily, with courses repeating every 28 days in the absence of disease progression or unacceptable toxicity. The study focused on breast cancer described as locally advanced or metastatic and resistant to previous tamoxifen. Its listed conditions include receptor-positive disease, recurrent disease, male breast carcinoma, and stage IIIB, stage IIIC, and stage IV breast cancer.
The registry records a start date of 2005-05, primary completion in 2011-07, and completed status. These dates describe the study record; they do not establish when individual participants began or ended treatment. The registry also lists laboratory biomarker analysis and a secondary outcome concerning changes in phosphorylation in tumor tissue for EGFR, HER2, AKT kinase, MAPK, ER-Ser118, and ER-SER167.
A single-group design can document outcomes in the treated participants, but it cannot by itself distinguish treatment effects from other explanations for those outcomes. There is no control arm in this record against which to compare response, adverse events, or biomarker changes. The registry record does not report a sample-size justification, detailed protocol, or further design rationale.
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 1 |
|---|---|
| STARTED | 19 |
| COMPLETED | 7 |
| NOT COMPLETED | 12 |
Reasons for not completing this period:
| Reason | Arm 1 |
|---|---|
| Adverse Event | 2 |
| Death | 8 |
| Withdrawal by Subject | 2 |
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 1 |
|---|---|---|
| Participants analysed | 19 | |
| Age, Continuous | years | 57 (32 to 84) |
| Age, Categorical: <=18 years | Participants | 0 |
| Age, Categorical: Between 18 and 65 years | Participants | 17 |
| Age, Categorical: >=65 years | Participants | 2 |
| Sex: Female, Male: Female | Participants | 19 |
| Sex: Female, Male: Male | Participants | 0 |
| Region of Enrollment: United States | participants | 19 |
6. Primary Endpoint
The registry lists the primary outcome as Tumor Response Rate (Complete and Partial) Assessed by Response Evaluation Criteria in Solid Tumors (RECIST), measured over 4 weeks.
| Element | Registry entry |
|---|---|
| Result type | Number |
| Measure of spread | 95% Confidence Interval |
| Unit | participants |
| Endpoint classification | Binary Endpoint |
The primary endpoint is tumor response, defined in the registry title as complete and partial response assessed by Response Evaluation Criteria in Solid Tumors (RECIST). It is recorded as a participant count, with a 95% confidence interval and a listed timeframe of 4 weeks. The registry record does not state the number of participants with complete response, the number with partial response, or a combined response result.
In general, a response endpoint classifies whether a participant's tumor meets specified criteria for shrinkage or disappearance. Combining complete and partial responses gives a binary outcome for each participant: a response is either counted or not counted under the endpoint definition. This can be useful in a treatment study because it gives a direct measure of tumor response during the specified assessment period. It is not, by itself, a measure of how long a response lasts, whether disease progression is delayed, or overall survival.
A confidence interval is intended to communicate uncertainty around an estimate, rather than just present a single number. Here, the record names a 95% confidence interval but supplies no interval limits or response estimate. The endpoint label and timeframe therefore describe what was intended to be assessed, not the result of that assessment. The registry record does not provide additional details about assessment procedures or the analysis population.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The registry record identifies a specific primary outcome and treatment context, but it does not report the primary outcome result. There is no posted count of participants with complete or partial response, no response estimate, and no confidence interval limits. As a result, the record cannot support a numerical description of the observed response or its precision. The absence of a posted result is not evidence that no responses occurred; it means the result is not reported in the registry record.
The study enrolled 19 participants in one treatment group. That enrollment figure is relevant to the scale of the study, but it cannot be used to infer the endpoint result. No outcome count should be reconstructed from enrollment alone. Likewise, the record does not supply participant-level observations from which to assess response timing, duration, or variation between participants.
The design also limits what any response result could establish. In a single-group study, a response observed during treatment can be described in that group, but there is no concurrent comparator to show how outcomes would differ with another treatment or without the combination. The design does not separate the contributions of lapatinib and tamoxifen. It also cannot establish from the posted information that any outcome was caused by the combination.
The listed secondary outcome concerns tumor-tissue phosphorylation changes in several markers. The registry does not report numerical changes or analyses for these markers. No relationship between biomarker changes and tumor response can be inferred from the outcome description alone.
Safety information is reported separately as adverse-event categories and percentages. Those figures describe the registry's serious adverse-event listings; they are not a comparison of risks between treatment groups. There is only one treatment group, and the record does not provide a control-group rate. A serious adverse-event term should not be read as proof that the treatment caused the event. The listed term Death NOS is an event-category label; the record's death field is null, so a death count cannot be stated from that field.
Overall, the posted material describes the trial design, endpoint, and some adverse-event listings, but does not give an efficacy analysis. Conclusions should therefore remain at the level of what was planned and what categories were recorded. No conclusion about the magnitude or precision of tumor response is available from the registry record.
9. Statistical Methods Explained
The registry describes a binary primary outcome: participants are counted according to whether they had a complete or partial tumor response under RECIST. The endpoint is expressed as a number of participants, and a 95% confidence interval is named. However, no endpoint count, estimate, interval limits, or analysis results are reported in the registry record. The methods below explain the statistical ideas relevant to this endpoint in general; they do not identify an unreported method used by the study.
What does a binary response measure?
In general, a binary outcome places each participant into one of two categories for a defined assessment: response or no response. The combined endpoint specified includes complete and partial response. A count records how many participants meet that definition. A response proportion can also be used to describe the share of an analyzed group meeting the definition, but no such proportion is reported in the registry record, and none can be derived from the endpoint description alone.
Endpoint definitions matter because they determine which observations count as events. RECIST is named in the endpoint, but the registry record does not provide the detailed assessment schedule, rules for handling unevaluable assessments, or the exact analysis population. Those details can affect how a response outcome is classified and summarized.
What does a confidence interval communicate?
In general, a confidence interval presents uncertainty around an estimate under a specified statistical method. A narrower interval indicates greater precision under that method, while a wider interval indicates less precision. The interval does not guarantee that the true value lies within its particular limits, and it does not eliminate uncertainty arising from study design, measurement, or selection of participants. Although the endpoint specifies a 95% confidence interval, its limits are not reported in the registry record, so its precision cannot be assessed.
For a binary outcome, interval methods can differ, especially when the number of participants or events is limited. The registry record does not name the interval method. It also does not supply an estimate or event count that could be used to independently reproduce an interval. No method should be attributed to the study beyond the reported reference to a 95% confidence interval.
What can the single-group design estimate?
In general, a single-group study can describe outcomes among participants receiving the studied treatment. It does not directly estimate a treatment contrast against a concurrent control. A treatment contrast requires outcomes from groups defined by different treatment strategies and a method for comparing them. Here, allocation is recorded as not applicable and the model is single group. Any response summary, if reported, would therefore describe this treated cohort rather than a randomized difference between treatments.
Small study size can also make estimates uncertain, particularly for outcomes that occur in relatively few participants. The registry reports enrollment of 19, but without an endpoint count and interval limits, the degree of uncertainty in the response outcome is not available. No sample-size justification is reported in the registry record.
How should planning illustrations be understood?
In general, a sample-size calculation is a planning exercise that describes how many participants might be needed under stated assumptions. The registry record does not report the trial's own sample-size justification or a planned power calculation. Any separate planning illustration based on an observed effect is not the same as an observed trial outcome, and it is not observed power. The record's stated illustration assumptions use a two-sided significance level of 0.05, equal allocation between two arms, a normal approximation, and an effect to detect expressed as a fraction of the observed effect. Those assumptions do not turn this single-group study into a two-arm comparison, and they do not provide evidence of the trial's design rationale.
What analysis details remain unknown?
The registry lists no analysis records. That indicates that analyses are not reported in the registry record; it does not establish whether analyses were conducted elsewhere. The record does not report the statistical test or model, the handling of missing or unevaluable response assessments, the analysis population, adjustment for multiple outcomes, or a prespecified statistical analysis plan. Without these details and the endpoint results, the primary outcome cannot be independently evaluated or reproduced from the registry record.
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 |
|---|---|---|---|---|---|---|
| Arm 1 | 17 | 1 | 5.9% | 0.1% to 28.7% | 1.0% to 27.0% | 1.4% to 27.3% |
R code and output
arm <- c("Arm 1")
n <- c(17)
events <- c(1)
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 Arm 1 17 1 5.9 0.1 28.7 1.0 27.0 1.4 27.311. Multiplicity, Missing Data and Analysis Populations
The registry identifies tumor response as the primary outcome and lists a secondary outcome concerning changes in phosphorylation in tumor tissue for EGFR, HER2, AKT kinase, MAPK, ER-Ser118, and ER-SER167. It reports two outcome measures in total, but does not provide numerical results or analysis records. The listed biomarkers make clear that more than one endpoint was considered; they do not establish how many separate statistical tests were performed.
When multiple outcomes or tests are examined, the chance of at least one apparently notable result can increase. In general, a multiplicity strategy may define which outcome is primary, adjust statistical testing, or emphasize estimation and uncertainty rather than isolated findings. The registry record does not report a multiplicity adjustment or a plan for prioritizing the secondary biomarker analyses. It is therefore not possible to determine whether any reported analyses accounted for multiple outcomes.
The record also does not describe how missing or unevaluable response assessments were handled. It does not specify whether the endpoint was analyzed among all enrolled participants, only those with an assessment, or another population. These omissions matter because the analysis population and missing-data rules can affect the interpretation of a binary response outcome.
No analysis records are listed, and the primary response result is not reported in the registry record. The missing analysis details should not be treated as proof that the investigators did not conduct analyses; they limit what can be learned from this registry record.
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 |
|---|---|---|---|
| Arm 1 | 19 | 19 | 100.0% |
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 1 | 17 of 19 |
Most frequent serious adverse event terms
| Event term | Organ system | Arm 1 |
|---|---|---|
| Diarrhea | Gastrointestinal disorders | 19 of 19 |
| Fatigue | General disorders | 13 of 19 |
| Death NOS | General disorders | 10 of 19 |
| Dyspnea | Respiratory, thoracic and mediastinal disorders | 5 of 19 |
| Cardiac disorders - Other, specify | Cardiac disorders | 4 of 19 |
| Hemolysis | Blood and lymphatic system disorders | 3 of 19 |
| Rash maculo-papular | Skin and subcutaneous tissue disorders | 3 of 19 |
| White blood cell decreased | Investigations | 3 of 19 |
| Hypocalcemia | Metabolism and nutrition disorders | 2 of 19 |
| Pericardial effusion | Cardiac disorders | 1 of 19 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Arm 1 |
|---|---|---|
| Anemia | Blood and lymphatic system disorders | 7 of 19 |
| Nausea | Gastrointestinal disorders | 7 of 19 |
| Anorexia | Metabolism and nutrition disorders | 6 of 19 |
| Dizziness | Nervous system disorders | 5 of 19 |
| Cough | Respiratory, thoracic and mediastinal disorders | 5 of 19 |
| Vomiting | Gastrointestinal disorders | 4 of 19 |
| Weight loss | Investigations | 4 of 19 |
| Pain in extremity | Musculoskeletal and connective tissue disorders | 4 of 19 |
| Hyperglycemia | Metabolism and nutrition disorders | 3 of 19 |
| Hypoalbuminemia | Metabolism and nutrition disorders | 3 of 19 |
Serious events with the highest arm-level rate: diarrhea (100.0%), fatigue (68.4%), death nos (52.6%), dyspnea (26.3%), cardiac disorders - other, specify (21.1%).
The registry lists serious adverse-event information for one group, with 19 participants at risk and 19 affected. It also records 19 at risk and 17 affected for other adverse events. These are group-level counts and do not identify which participants experienced each listed term. The death field is null, so a death count is not available from that field.
The serious-event terms are listed with percentages: Diarrhea, 100.0%; Fatigue, 68.4%; Death NOS, 52.6%; Dyspnea, 26.3%; Cardiac disorders - Other, specify, 21.1%; and Hemolysis, 15.8%. These percentages should be read as registry listings, not as a comparison with another treatment group. The record does not provide a comparator, and the percentages alone do not establish that treatment caused an event.
In general, adverse-event categories can overlap: a participant may be represented under more than one term. The listed percentages should not be added together to produce a total. Death NOS is a category label in the serious-event list; it should not be substituted for a separately reported death count. The registry does not provide further information about event timing, duration, or individual-level attribution.
13. What the Result Does, and Does Not, Mean
The record documents a phase II, single-group study of lapatinib with tamoxifen in breast cancer described as resistant to previous tamoxifen. It gives the enrollment, treatment schedule, primary endpoint definition, and selected serious adverse-event listings. These are useful for understanding what the study set out to examine and what kinds of information were entered in the registry.
The primary endpoint result is not reported in the registry record. There is no response count, response rate, or confidence interval to interpret. The study's enrollment of 19 does not reveal how many participants responded. Consequently, the posted record cannot quantify the response observed in the treatment group or indicate how precisely it was estimated.
Even if a response estimate were available, the design would still be limited to describing outcomes in a single treated group. Without a concurrent comparator, it could not determine the difference in outcomes between the combination and another treatment. It could not isolate the contribution of either drug, nor show that a response was caused by the treatment rather than other influences.
The adverse-event percentages describe listed serious-event terms in the treatment group. They do not establish comparative safety or causation. The registry's Death NOS category is not a substitute for a reported death count, which is null in the group record.
The registry record also does not report the statistical analysis details needed to assess the endpoint's analysis population, missing assessments, or multiplicity handling. These limits do not erase the design and outcome definitions that are recorded, but they constrain interpretation. The appropriate reading is descriptive: the record identifies a planned treatment and endpoint and reports selected safety categories, while leaving the primary response estimate and key analysis details unreported.
14. Why This Trial Matters Statistically
This trial is statistically notable for the contrast between a clearly identified primary endpoint and the absence of a posted result for that endpoint. Tumor response is specified as complete and partial response under RECIST, with a 95% confidence interval and a 4-week timeframe. Yet no response count, estimate, or interval limits appear in the registry record. This illustrates why an endpoint definition alone cannot answer the research question: the observed outcome and its uncertainty are also needed.
The single-group structure is central to interpretation. It allows the study to describe outcomes among participants receiving lapatinib and tamoxifen, but it does not create a randomized treatment contrast. Any result from such a design would be a cohort description, not an estimate of the difference between the combination and a control treatment. The registry's allocation and masking fields are consistent with this distinction.
The record also lists biomarker outcomes alongside the clinical response endpoint. Multiple outcomes can raise questions about which analyses were planned, how they were prioritized, and whether multiplicity was addressed. The registry does not provide those details or analysis results. This is a reminder that outcome lists do not by themselves reveal the statistical plan.
Finally, safety listings require careful separation of category labels, participant counts, and causal interpretation. The record gives serious adverse-event terms and percentages for a single group, but no comparison group. These figures can describe what was recorded, while leaving comparative safety and attribution unresolved. Taken together, the trial demonstrates how design, endpoint reporting, and analysis transparency determine the scope of conclusions that can be drawn from a registry record.
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 main limitation for interpreting efficacy is that the registry record does not report the primary tumor-response result. It gives no complete-response count, partial-response count, combined response count, response estimate, or confidence interval limits. The endpoint timeframe is listed as 4 weeks, but further assessment details are not reported.
Because this is a single-group study with no comparator, it cannot estimate a treatment difference against another strategy. The study also cannot separate the effects of lapatinib and tamoxifen. The registry record does not report a sample-size justification, detailed statistical analysis plan, or rationale for the enrollment target, so those aspects of design cannot be assessed.
Important analysis details are not reported, including the analysis population, handling of missing or unevaluable response assessments, and statistical methods used. The record lists a secondary biomarker outcome but does not provide its results or explain whether any multiplicity approach was planned. The absence of registry analysis records limits independent evaluation but does not establish whether analyses occurred outside the registry.
The safety information is also limited to a single treatment group and listed event categories. It does not provide a control-group comparison, establish causation, or give additional detail on timing and duration. Although the group record includes a null death field, the serious-event list includes Death NOS; that category does not permit a separate death count to be inferred.
16. Related Tutorials
17. Related Statistical Calculators
18. Sources
- ClinicalTrials.gov: Lapatinib and Tamoxifen in Treating Patients With Locally Advanced or Metastatic Breast Cancer That Did Not Respond to Previous Tamoxifen — NCT00118157.
- Registry record last updated 2017-12-04; status last verified 2017-10.
- Results first posted 2014-12-03.
- 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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19. Record Summary
The registry describes a completed phase II, single-group study of lapatinib ditosylate and tamoxifen citrate for breast cancer that had not responded to previous tamoxifen. Enrollment was 19. The treatment description specifies both drugs taken by mouth daily, with courses repeating every 28 days while there was no disease progression or unacceptable toxicity. The registry records a start date of 2005-05 and primary completion in 2011-07.
The primary outcome was complete or partial tumor response assessed by RECIST, with a listed timeframe of 4 weeks and a 95% confidence interval. The response result and analysis details are not reported in the registry record. The record lists a secondary tumor-tissue phosphorylation outcome and serious adverse-event terms for the treatment group. There is no comparator group, so the record does not establish comparative efficacy or safety.