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 Pazopanib Plus Lapatinib Compared To Lapatinib Alone In Subjects With Advanced Or Metastatic Breast Cancer (NCT00347919), a randomized phase 2 study. The primary outcome is Percentage of Participants With Progressive Disease at Week 12 in Cohort 1.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT00347919 |
| Phase | Phase 2 |
| Condition | Neoplasms, Breast |
| Allocation | Randomized |
| Design model | Parallel |
| Masking | None (open label) |
| Enrollment | 189 |
| Arms in the primary outcome | n/a |
| Lead sponsor | GlaxoSmithKline |
| Results posted | Yes |
2. Clinical Question
Population
Participants with advanced or metastatic breast cancer whose tumors were ErbB2 FISH-positive. The primary endpoint population was Cohort 1’s modified intent-to-treat population: randomized participants with central confirmation of ErbB2 FISH positivity.
Intervention
In Cohort 1, the combination was oral lapatinib 1000 mg and oral pazopanib 400 mg, taken together once daily. Cohort 2 received a different combination dose: lapatinib 1500 mg and pazopanib 800 mg once daily.
Comparator
The monotherapy arm received oral lapatinib 1500 mg once daily. The primary endpoint is specifically defined for Cohort 1; the registry does not report a single primary comparison result for that endpoint.
Primary question
What percentage of participants in Cohort 1 had progressive disease at Week 12? The registry defines progression using RECIST and also classifies unknown or missing Week 12 responses as progressive disease. It does not report the observed percentages or a treatment-effect estimate for this endpoint.
The trial’s broad aim was to compare the efficacy and safety of pazopanib combined with lapatinib against lapatinib alone in locally advanced or metastatic breast cancer with ErbB2 overexpression. The official title specifies first-line therapy and ErbB2 FISH-positive tumors. Those details define the clinical setting and eligibility focus, but they do not establish the magnitude or direction of any treatment difference.
The primary endpoint is a binary participant-level classification at a fixed assessment time: progressive disease versus not classified as progressive disease. The registry says response was assessed by an independent radiologist and an investigator. Because missing or unknown Week 12 responses were counted as progression, the endpoint incorporates both disease assessments and the handling of unavailable assessments. The registry does not give the numbers classified into each endpoint category, so the central comparison cannot be quantified from the record.
3. Trial Design
This was a randomized, open-label, parallel-group Phase II trial sponsored by GlaxoSmithKline. The registry records enrollment of 189 participants and lists the study as completed. The start is recorded as 2006-07 and primary completion as 2008-08. The study was conducted at multiple centers, as stated in its official title.
The treatment structure included a lapatinib-alone arm and two combination cohorts. The monotherapy arm used lapatinib 1500 mg once daily. Cohort 1 combined lapatinib 1000 mg with pazopanib 400 mg once daily; Cohort 2 combined lapatinib 1500 mg with pazopanib 800 mg once daily. Thus, the combination was not represented by a single regimen: the two cohorts differed in the listed doses of both drugs. The primary endpoint is designated for Cohort 1, so it should not be described as an endpoint pooled across both combination cohorts.
Randomization supports a planned comparison between assigned treatment groups, but the record does not report the allocation ratio, the randomization procedure, or whether allocation was stratified. Masking is listed as none, so the study was open-label rather than blinded. The record does not explain how this design feature was addressed in assessment or analysis. It identifies response assessment by an independent radiologist and by an investigator, but does not report whether either assessment was used as the primary analysis for the endpoint or how disagreements were handled.
The record does not report the rationale for the enrollment target, a formal sample-size justification, details of the statistical analysis plan, or whether any interim analyses were conducted. These omissions mean the observed enrollment alone cannot establish whether the study was designed to detect a particular treatment difference with a particular precision. Cohort-specific outcome counts and estimates are also not reported for the primary endpoint, limiting assessment of the randomized comparison.
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: Female par. with \>=18 years of age with histologically confirmed invasive breast cancer were enrolled in the study. Total 189 par. (Cohort 1, combination n = 76, lapatinib n = 73; Cohort 2, n = 40) received study drug.
Overall Study
| Stage | Cohort 1: Lapatinib 1500 mg | Cohort 1: Lapatinib 1000 mg/Pazopanib 400 mg | Cohort 2: Lapatinib 1500 mg/Pazopanib 800 mg |
|---|---|---|---|
| STARTED | 73 | 76 | 40 |
| COMPLETED | 2 | 0 | 2 |
| NOT COMPLETED | 71 | 76 | 38 |
Reasons for not completing this period:
| Reason | Cohort 1: Lapatinib 1500 mg | Cohort 1: Lapatinib 1000 mg/Pazopanib 400 mg | Cohort 2: Lapatinib 1500 mg/Pazopanib 800 mg |
|---|---|---|---|
| Lost to Follow-up | 11 | 13 | 0 |
| Withdrawal by Subject | 6 | 8 | 0 |
| Physician Decision | 1 | 1 | 0 |
| Sponsor terminated study | 15 | 10 | 16 |
| Death | 35 | 42 | 19 |
| Par. Started Other Treatment | 1 | 1 | 1 |
| Missing | 2 | 1 | 2 |
Analysis population for the primary outcome, as defined in the registry: Cohort 1: Modified Intent-to-Treat (ITT) Population (all randomized, centrally confirmed, ErbB2 FISH-positive participants).
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 | Cohort 1: Lapatinib 1500 mg | Cohort 1: Lapatinib 1000 mg/Pazopanib 400 mg | Cohort 2: Lapatinib 1500 mg/Pazopanib 800 mg | Total |
|---|---|---|---|---|---|
| Participants analysed | 72 | 69 | 36 | 177 | |
| Age, Continuous | years | 53.5 (SD 11.20) | 52.1 (SD 12.76) | 54.1 (SD 12.93) | 52.8 (SD 11.97) |
| Sex: Female, Male: Female | Participants | 72 | 69 | 36 | 177 |
| Sex: Female, Male: Male | Participants | 0 | 0 | 0 | 0 |
| Race/Ethnicity, Customized: African American/African Heritage | participants | 0 | 1 | 0 | 1 |
| Race/Ethnicity, Customized: American Indian or Alaska Native | participants | 20 | 18 | 0 | 38 |
| Race/Ethnicity, Customized: Asian | participants | 33 | 30 | 3 | 66 |
| Race/Ethnicity, Customized: White | participants | 19 | 18 | 32 | 69 |
| Race/Ethnicity, Customized: Other | participants | 0 | 1 | 0 | 1 |
| Race/Ethnicity, Customized: Unknown | participants | 0 | 1 | 1 | 2 |
| Child-Bearing Potential: Post-Menopausal | participants | 49 | 46 | 22 | 117 |
| Child-Bearing Potential: Sterile (of child-bearing age) | participants | 3 | 2 | 5 | 10 |
| Child-Bearing Potential: Potentially able to bear children | participants | 20 | 21 | 9 | 50 |
6. Primary Endpoint
The registry lists the primary outcome as Percentage of Participants With Progressive Disease at Week 12 in Cohort 1, measured over Week 12.
| 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 with progressive disease at Week 12 in Cohort 1. It expresses the proportion of the specified population who met the endpoint definition at a fixed time after randomization. The registry defines progressive disease under RECIST as a >=20% increase in target lesions. It also classifies a Week 12 response that is unknown or missing as progressive disease. Response was determined by an independent radiologist and by an investigator.
A fixed-time percentage is useful because it gives a direct summary of how many participants met a clinically interpretable disease-status definition at a common assessment point. It is a binary outcome: each participant is classified according to whether the endpoint definition is met. This can make an arm-level comparison easier to interpret than a collection of individual lesion measurements, but it does not preserve all information about the degree or timing of change.
The handling of unknown or missing assessments is part of the endpoint itself, not merely a technical detail. Counting such cases as progressive disease can affect the percentage, particularly if missing assessments differ between treatment groups. The registry does not report how many Week 12 responses were missing or unknown, nor does it report the endpoint percentages or their uncertainty. Consequently, the record supports describing the endpoint definition, but not estimating the treatment contrast or its precision.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The registry identifies progressive disease at Week 12 in Cohort 1 as the primary endpoint, but it does not report the outcome values required to interpret that endpoint comparatively. There are no arm-specific percentages, participant counts by endpoint category, confidence intervals, or treatment-effect estimate in the record summarized for this analysis. A numerical statement about which arm had more or less progression, or by how much, therefore cannot be made. The primary endpoint result is not reported in the registry record.
For a binary endpoint, interpretation ordinarily begins with the proportion meeting the definition in each randomized group. A contrast between those proportions describes the observed difference in the endpoint frequency. Its uncertainty is also important: a confidence interval indicates the range of effect sizes reasonably compatible with the data under the analysis assumptions. A point estimate without an interval can conceal substantial imprecision, while an interval that includes effects in different directions may leave the comparison uncertain. These are general principles; no such estimate or interval is reported for this endpoint.
The registry’s endpoint definition treats unknown or missing Week 12 responses as progressive disease. That convention can make the endpoint sensitive to differences in assessment availability across arms. If unavailable assessments occur more often in one group, classifying every such case as progression could influence the between-group comparison. The record does not state the number of missing or unknown responses, whether missingness differed by group, or whether sensitivity analyses explored alternative handling. It is therefore not possible to assess the practical influence of this rule from the registry record.
The endpoint population is Cohort 1’s modified intent-to-treat population, described as all randomized, centrally confirmed, ErbB2 FISH-positive participants. That definition matters: the result, if available, would apply to the specified population and endpoint, not automatically to every participant enrolled or to Cohort 2. The record does not provide the endpoint denominators or a detailed account of exclusions between randomization and analysis.
Safety counts are reported separately. In Cohort 1, serious adverse events affected 10 participants in the lapatinib 1500 mg group and 18 in the lapatinib 1000 mg/pazopanib 400 mg group; the corresponding numbers at risk are 73 and 76. In Cohort 2, 13 participants were reported with serious adverse events among 40 at risk. These counts describe the registry’s safety reporting and do not substitute for the missing primary endpoint comparison. They should not be interpreted as evidence for or against efficacy.
The study’s Phase II designation and randomized open-label structure describe its development stage and design, not the result. Without the reported endpoint estimates, their uncertainty, and the analysis details, the registry record does not support a conclusion about the size, direction, or precision of the primary treatment comparison. Any sample-size calculations displayed alongside the results are planning illustrations based on stated assumptions, not observed power and not a substitute for the trial’s own design rationale.
9. Statistical Methods Explained
Statistical methods are useful only when their target, population, and assumptions are clear. In this trial, the primary target is a percentage of participants with progressive disease at Week 12 in Cohort 1’s modified intent-to-treat population. The record gives the outcome definition, but not the observed percentages or a treatment-effect estimate. The concepts below explain how such an endpoint is generally analyzed; they do not describe unreported procedures from this trial.
What does a percentage estimate?
For a binary outcome, each participant is classified into an endpoint category, and the group percentage is the proportion meeting the event definition. Here, the event is progressive disease under the registry’s rule. A group percentage describes the observed frequency in that group; it does not by itself establish how much the groups differ. A comparison requires both groups’ results and a specified contrast. The registry record does not report those results for the primary endpoint.
A percentage also depends on its denominator. The relevant analysis population is described as all randomized, centrally confirmed, ErbB2 FISH-positive participants in Cohort 1. If participants are excluded from the analysis or endpoint assessments are unavailable, the denominator and classification rules affect the estimate. Although the registry says unknown or missing Week 12 responses were classified as progressive disease, it does not report how many such responses occurred or how denominators were handled in the final analysis.
What does uncertainty add?
A confidence interval communicates sampling uncertainty around an estimate. General interpretation: a narrower interval indicates greater precision under the model used, while a wider interval indicates that a broader range of effects remains compatible with the data. An interval does not account automatically for every possible source of bias, such as outcome misclassification or a difference in assessment availability. No confidence interval for the primary endpoint is reported in the registry record.
A test of statistical significance addresses compatibility of the data with a specified null hypothesis under a statistical model. A p-value is not the probability that a treatment works, nor does it quantify the clinical importance of an effect. Its interpretation depends on the analysis and the comparison being tested. The registry record does not report a primary-endpoint p-value, test specification, or statistical analysis plan. It is not appropriate to infer these details from the trial’s randomized design or Phase II label.
Why does the endpoint definition matter?
The endpoint is based on a RECIST progression rule, with a >=20% increase in target lesions defining progressive disease. It also includes unknown and missing Week 12 responses in the progression category. This approach ensures that missing or unknown assessments are not simply omitted from the event category, but it can make the estimated percentage reflect assessment availability as well as disease status. General statistical practice is to examine how missing data are distributed and to consider whether conclusions depend on the chosen rule. The registry does not report such an examination or sensitivity analysis.
The record names an independent radiologist and an investigator as response assessors. Independent review can be useful in outcome assessment, especially when treatment assignment is not masked, but the registry does not state which assessment governed the primary analysis, whether assessments were reconciled, or how any disagreement was treated. Those operational details should not be presumed.
How should design-based comparisons be understood?
Random allocation is intended to support a fair comparison by balancing, on average, prognostic characteristics across assigned groups. It does not guarantee balance in every realized trial, and it does not remove uncertainty. Open-label assignment means masking was absent; awareness of treatment can potentially affect behaviors, assessment, or decisions. The registry identifies independent radiologist and investigator assessments, but does not report how masking-related risks were handled in the analysis. These are general considerations, not claims that bias occurred in this trial.
The two combination cohorts used different dose combinations. Cohort 1 and Cohort 2 therefore should not be merged conceptually as if they received the same regimen. The primary endpoint is explicitly attached to Cohort 1. Comparisons involving Cohort 2, or a pooled estimate across combination cohorts, would require their own stated estimand and analysis; neither is reported for the primary endpoint in the record.
What do planning calculations mean?
A sample-size calculation is a prospective planning exercise that depends on assumptions about the treatment effect, variability or event frequency, significance level, allocation, and analysis method. The registry’s planning illustration is described as based on the observed effect, with a two-sided significance level of 0.05, equal allocation, and a normal approximation; the effect to detect is a stated fraction of the observed effect. Such calculations are illustrations, not evidence that the trial was planned with those assumptions. They are not observed power, and the registry does not report the trial’s own sample-size justification.
For non-time-to-event outcomes, the stated convention for planning figures is participants per arm. The record distinguishes that convention from time-to-event calculations, which use the total number of events. These conventions describe how planning quantities should be read, not a result from the primary endpoint. No planning output or trial-specific power claim should be inferred from the enrollment count alone.
10. Multiplicity, Missing Data and Analysis Populations
The registry lists several secondary outcomes, including overall survival for Cohort 1, response at Week 12 for Cohort 1 and Cohort 2, duration and time to response, and the percentage with progressive disease at Week 12. When a trial evaluates multiple outcomes, cohorts, time points, or comparisons, the chance of at least one apparently unusual result can increase if each is tested separately. General approaches include prespecifying a primary hypothesis, adjusting tests, or interpreting secondary analyses as exploratory. The registry record does not report a multiplicity strategy, a hierarchy of tests, or how secondary findings were to be interpreted.
The record identifies six outcome measures and three analyses, but does not provide enough detail to reconstruct the full analysis family or determine which tests were formally confirmatory. The primary endpoint is specified for Cohort 1. The listed secondary outcomes span cohorts and time points, so their results should not be treated as interchangeable with the primary question. No multiplicity-adjusted estimates or testing procedure are reported for the primary endpoint.
Missingness is particularly relevant because unknown or missing Week 12 responses were counted as progressive disease. The registry does not report the number of missing assessments, reasons for missingness, or whether assessment availability differed by group. It also does not report sensitivity analyses under alternative missing-data assumptions. This prevents readers from determining how much the endpoint result, if available, might depend on the classification rule.
The primary analysis population is described as Cohort 1’s modified intent-to-treat population, defined by randomization and central ErbB2 FISH confirmation. The record does not provide a participant flow or a detailed account of departures from that population. It therefore does not permit a complete assessment of exclusions or their potential effect on comparability.
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 |
|---|---|---|---|
| Cohort 1: Lapatinib 1500 mg | 10 | 73 | 13.7% |
| Cohort 1: Lapatinib 1000 mg/Pazopanib 400 mg | 18 | 76 | 23.7% |
| Cohort 2: Lapatinib 1500 mg/Pazopanib 800 mg | 13 | 40 | 32.5% |
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 |
|---|---|
| Cohort 1: Lapatinib 1500 mg | 63 of 73 |
| Cohort 1: Lapatinib 1000 mg/Pazopanib 400 mg | 71 of 76 |
| Cohort 2: Lapatinib 1500 mg/Pazopanib 800 mg | 39 of 40 |
Most frequent serious adverse event terms
| Event term | Organ system | Cohort 1: Lapatinib 1500 mg | Cohort 1: Lapatinib 1000 mg/Pazopanib 400 mg | Cohort 2: Lapatinib 1500 mg/Pazopanib 800 mg |
|---|---|---|---|---|
| Diarrhoea | Gastrointestinal disorders | 2 of 73 | 1 of 76 | 3 of 40 |
| Pyrexia | General disorders | 0 of 73 | 1 of 76 | 4 of 40 |
| Ejection fraction decreased | Investigations | 0 of 73 | 3 of 76 | 2 of 40 |
| Dehydration | Metabolism and nutrition disorders | 3 of 73 | 0 of 76 | 1 of 40 |
| Hepatic enzyme increased | Investigations | 0 of 73 | 0 of 76 | 3 of 40 |
| Dyspnoea | Respiratory, thoracic and mediastinal disorders | 2 of 73 | 1 of 76 | 0 of 40 |
| Pleural effusion | Respiratory, thoracic and mediastinal disorders | 1 of 73 | 2 of 76 | 0 of 40 |
| Anaemia | Blood and lymphatic system disorders | 0 of 73 | 2 of 76 | 0 of 40 |
| Left ventricular dysfunction | Cardiac disorders | 0 of 73 | 2 of 76 | 0 of 40 |
| Gastroenteritis | Infections and infestations | 1 of 73 | 1 of 76 | 0 of 40 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Cohort 1: Lapatinib 1500 mg | Cohort 1: Lapatinib 1000 mg/Pazopanib 400 mg | Cohort 2: Lapatinib 1500 mg/Pazopanib 800 mg |
|---|---|---|---|---|
| Diarrhoea | Gastrointestinal disorders | 41 of 73 | 52 of 76 | 34 of 40 |
| Nausea | Gastrointestinal disorders | 13 of 73 | 23 of 76 | 28 of 40 |
| Rash | Skin and subcutaneous tissue disorders | 21 of 73 | 21 of 76 | 16 of 40 |
| Aspartate aminotransferase increased | Investigations | 13 of 73 | 26 of 76 | 15 of 40 |
| Alanine aminotransferase increased | Investigations | 13 of 73 | 25 of 76 | 15 of 40 |
| Fatigue | General disorders | 7 of 73 | 12 of 76 | 23 of 40 |
| Decreased appetite | Metabolism and nutrition disorders | 10 of 73 | 17 of 76 | 14 of 40 |
| Hypertension | Vascular disorders | 4 of 73 | 20 of 76 | 15 of 40 |
| Vomiting | Gastrointestinal disorders | 6 of 73 | 15 of 76 | 13 of 40 |
| Dysgeusia | Nervous system disorders | 1 of 73 | 12 of 76 | 12 of 40 |
Serious events with the highest arm-level rate: pyrexia (10.0%), diarrhoea (7.5%), hepatic enzyme increased (7.5%), ejection fraction decreased (5.0%), dehydration (4.1%).
The registry reports serious adverse-event counts by group. In Cohort 1, the lapatinib 1500 mg group had 10 participants with serious adverse events among 73 at risk; the lapatinib 1000 mg/pazopanib 400 mg group had 18 among 76 at risk. In Cohort 2, the lapatinib 1500 mg/pazopanib 800 mg group had 13 among 40 at risk. These are counts of affected participants and their reported group denominators, not estimates of the primary efficacy endpoint.
The registry also lists serious adverse-event terms with percentages: Pyrexia, 10.0%; Diarrhoea, 7.5%; Hepatic enzyme increased, 7.5%; Ejection fraction decreased, 5.0%; Dehydration, 4.1%; and Dyspnoea, 2.7%. The record does not specify in this listing how each percentage maps to a particular cohort, so a cohort-specific interpretation should not be assumed. It does not report death counts in the adverse-event group records.
Counts and percentages describe what was recorded under the registry’s reporting conventions. They do not, by themselves, establish that an event was caused by treatment or permit a complete comparison of safety. Differences in exposure duration, event definitions, follow-up, and reporting can matter, but these details are not reported in the registry record. The listed serious-event information should therefore be read descriptively, not as a causal estimate or a comprehensive account of risk.
12. What the Result Does, and Does Not, Mean
The record establishes the question the trial set out to address: comparison of a pazopanib and lapatinib combination with lapatinib alone in advanced or metastatic breast cancer, with a primary Week 12 progressive-disease endpoint in Cohort 1. It also documents a randomized, open-label, parallel-group Phase II design and defines the primary endpoint population and event classification. These features allow readers to understand the intended comparison and the way the endpoint was framed.
The record does not report the primary endpoint percentages, group counts, confidence intervals, or treatment-effect estimate. It therefore cannot establish whether the groups differed on Week 12 progression, the direction of any difference, or how precise an estimate might be. The absence of a reported endpoint result is not evidence that the treatments were equivalent, nor does it show that one approach was superior. It means the registry record does not provide the numerical result needed to answer that comparison.
The endpoint is also specific to Cohort 1 and to a population with central confirmation of ErbB2 FISH positivity. It should not be generalized automatically to Cohort 2, to all enrolled participants, or to other clinical settings. Cohort 2 used different combination doses, and the record does not report a primary endpoint result for a pooled combination group.
The serious adverse-event counts provide descriptive safety information, but they do not resolve the efficacy question. The record does not supply detailed exposure or follow-up information, a full account of adverse-event attribution, or death counts in the group records. The serious-event percentages are not assigned to specific cohorts in the listing. These limitations constrain direct safety comparisons.
Any planning sample-size illustrations are prospective calculations under stated assumptions, not observed power and not evidence about the actual treatment effect. The registry does not report its own sample-size justification or full analysis plan. Overall, the record supports a precise description of the trial question, design, endpoint definition, and some safety counts; it does not support a quantitative conclusion about the primary efficacy comparison.
13. Why This Trial Matters Statistically
This trial is statistically informative as an example of why a defined endpoint and a reported result are both necessary. The registry gives a specific Week 12 classification rule for progressive disease, identifies the Cohort 1 analysis population, and states that unknown or missing assessments count as progression. Those details help define what a percentage would represent. Without the actual category counts and treatment contrast, however, the clinical question remains quantitatively unanswered by the registry record.
The endpoint also illustrates how missing-data rules can be embedded directly into outcome definitions. Counting missing or unknown assessments as progression means the endpoint is not simply a summary of observed tumor measurements. It combines the disease-status rule with a classification for unavailable assessments. That makes the number and distribution of missing assessments important to interpretation, yet those details are not reported in the registry record.
The trial’s two combination cohorts add another design consideration. They used different doses, while the primary endpoint is specified for Cohort 1. Statistical interpretation must preserve that distinction rather than treating all combination participants as one uniform group. The registry’s outcome descriptions span cohorts and time points, which also makes transparent reporting of the analysis hierarchy and multiplicity approach important; those methods are not reported.
Finally, the serious adverse-event counts demonstrate the value of reporting denominators alongside event counts. The record gives counts affected and numbers at risk for each listed group, but lacks enough accompanying detail to make a complete comparative safety assessment. This example underscores that trial registration can clarify design and definitions, while incomplete outcome reporting limits estimation, precision assessment, and practical interpretation.
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 interpreting the primary question is that the registry record does not report the Week 12 progressive-disease results. Without arm-specific counts or percentages and a treatment-effect estimate, neither the direction nor the magnitude of the primary comparison can be evaluated. The record also does not give confidence intervals or a primary-endpoint p-value, so the precision and statistical compatibility of the result cannot be assessed.
The endpoint population is defined, but participant flow and final endpoint denominators are not reported. The rule classifying unknown or missing responses as progression is explicit, yet the number of such assessments, their reasons, and their distribution by group are not reported. The impact of this rule cannot therefore be examined. No sensitivity analysis under other missing-data assumptions is described.
The study was open-label, and the record names both an independent radiologist and an investigator as response assessors. It does not specify which assessment posted the primary result, how disagreements were resolved, or how the absence of masking was addressed analytically. The randomization procedure and allocation ratio are also not reported.
The registry lists multiple secondary outcomes across cohorts and time points, but does not report the planned multiplicity strategy or a full statistical analysis plan. It does not provide the trial’s sample-size rationale, interim-analysis information, or enough detail to reconstruct all analysis populations. Cohort 1 and Cohort 2 used different combination doses, and a primary result for Cohort 1 should not be generalized to Cohort 2 without supporting evidence.
Safety reporting is likewise limited: event counts are available, but detailed exposure and follow-up information, cohort attribution for the listed serious-event percentages, and death counts are not reported in the registry record.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Pazopanib Plus Lapatinib Compared To Lapatinib Alone In Subjects With Advanced Or Metastatic Breast Cancer — NCT00347919.
- Registry record last updated 2016-02-25; status last verified 2016-01.
- Results first posted 2011-02-21.
- 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
NCT00347919 is a completed, randomized, open-label, parallel-group Phase II trial sponsored by GlaxoSmithKline. It studied pazopanib plus lapatinib compared with lapatinib alone in advanced or metastatic breast cancer with ErbB2-positive tumors. Enrollment was 189; the registry records the start as 2006-07 and primary completion as 2008-08.
The primary endpoint was the percentage with progressive disease at Week 12 in Cohort 1’s modified intent-to-treat population. The registry defines progression using RECIST and classifies unknown or missing Week 12 responses as progression. It does not report the endpoint result or a quantitative comparison.
Serious adverse-event counts are reported for the three listed groups, alongside a list of serious-event terms and percentages. The record does not provide enough detail to interpret those percentages by cohort or make a complete comparative safety assessment. The trial design and endpoint definitions are documented, but the primary efficacy result and several analysis details are not reported in the registry record.