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 A Study to Compare the Safety and Efficacy of an Aromatase Inhibitor in Combination With Lapatinib, Trastuzumab or Both for the Treatment of Hormone Receptor Positive, HER2+ Metastatic Breast Cancer (NCT01160211), a randomized phase 3 study. The primary outcome is Progression Free Survival (PFS) Events in Lapatinib + Trastuzumab + Aromatase Inhibitor (AI) vs. Trastuzumab + Aromatase Inhibitor (AI).
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT01160211 |
| Phase | Phase 3 |
| Condition | Neoplasms, Breast |
| Allocation | Randomized |
| Design model | Parallel |
| Masking | None (open label) |
| Enrollment | 369 |
| Arms in the primary outcome | n/a |
| Lead sponsor | Novartis Pharmaceuticals |
| Results posted | Yes |
2. Clinical Question
Population
Postmenopausal participants with hormone receptor-positive, HER2-positive metastatic breast cancer who had received prior trastuzumab and endocrine therapies. The study concerned first- or second-line treatment. The primary outcome population was the Intent-to-Treat population with available data for the outcome measure.
Intervention
Lapatinib plus trastuzumab plus an aromatase inhibitor. The regimen description specifies lapatinib 1000 mg by mouth once daily, trastuzumab with a loading dose of 8 mg/kg followed by 6 mg/kg intravenously every 3 weeks, and an investigator-selected aromatase inhibitor by mouth once daily.
Comparator
The primary comparison was the combination of trastuzumab plus an aromatase inhibitor. A separate randomized group received lapatinib plus an aromatase inhibitor, so the study included three treatment groups overall.
Primary question
How did the number of participants with investigator-assessed progression-free survival events compare between the group receiving all three drugs and the group receiving trastuzumab plus an aromatase inhibitor? The registry defines an event as progression or death from any cause, whichever occurred first, from randomization through assessment up to approximately 5 years.
This question focuses on whether progression or death occurred during follow-up, rather than on tumor response alone. The trial also listed overall survival, response, clinical benefit, time to response, duration of response and quality-of-life outcomes as secondary outcomes. The registry record does not report the primary comparison’s event counts or comparative estimate in the information available for this analysis. Therefore, the clinical question can be described, but the size and precision of the observed difference cannot be characterized from these registry entries.
3. Trial Design
This was a randomized, open-label, parallel-group Phase III trial with 369 participants enrolled. The registry lists the study as completed. It began on 2011-05-05, and primary completion was 2016-03-11. Novartis Pharmaceuticals is listed as the sponsor. The registry describes the eligible population as postmenopausal participants with hormone receptor-positive, HER2-positive metastatic breast cancer who had received prior trastuzumab and endocrine therapies.
Participants were assigned among three treatment groups. One received lapatinib, trastuzumab and an aromatase inhibitor; one received trastuzumab and an aromatase inhibitor; and one received lapatinib and an aromatase inhibitor. The aromatase inhibitor was selected by the investigator. The combination and dosing descriptions are stated in the registry, but the actual number randomized to each group is not reported in the registry record in the registry record for this analysis.
Randomization supports comparisons between assigned groups by reducing systematic differences in baseline characteristics on average. Open-label means treatment assignment was not masked. The primary outcome was assessed by investigators, so knowledge of treatment assignment could potentially influence assessment; the registry record does not describe procedures used to reduce this possibility. It also does not report the randomization method, allocation concealment details, stratification factors or protocol deviations.
The primary endpoint was the number of participants with progression-free survival events in the triple-treatment group compared with the trastuzumab-plus-aromatase-inhibitor group. Secondary outcomes covered survival, tumor response, clinical benefit, response timing, response duration and quality of life. The registry record does not report a detailed statistical analysis plan or explain the role of the lapatinib-plus-aromatase-inhibitor group in the primary 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.
Overall Study
| Stage | Lapatinib + Trastuzumab + Aromatase Inhibitor (AI) | Lapatinib + Aromatase Inhibitor (AI) | Trastuzumab + Aromatase Inhibitor (AI) |
|---|---|---|---|
| STARTED | 124 | 123 | 122 |
| Safety Set | 123 | 123 | 121 |
| COMPLETED | 64 | 64 | 55 |
| NOT COMPLETED | 60 | 59 | 67 |
Reasons for not completing this period:
| Reason | Lapatinib + Trastuzumab + Aromatase Inhibitor (AI) | Lapatinib + Aromatase Inhibitor (AI) | Trastuzumab + Aromatase Inhibitor (AI) |
|---|---|---|---|
| Subject Reached Protocol-Defined Stopping Criteria | 49 | 49 | 59 |
| Lost to Follow-up | 4 | 8 | 4 |
| Physician Decision | 1 | 0 | 0 |
| Withdrawal by Subject | 4 | 2 | 2 |
| Data unavailable due to regulatory issues | 2 | 0 | 2 |
Analysis population for the primary outcome, as defined in the registry: Participants in the Intent-to-Treat (ITT) Population with available data for the outcome measure.
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 | Lapatinib + Trastuzumab + Aromatase Inhibitor (AI) | Lapatinib + Aromatase Inhibitor (AI) | Trastuzumab + Aromatase Inhibitor (AI) | Total |
|---|---|---|---|---|---|
| Participants analysed | 124 | 123 | 122 | 369 | |
| Age, Continuous | Years | 56.9 (SD 11.15) | 57.1 (SD 9.98) | 54.9 (SD 10.10) | 56.3 (SD 10.45) |
| Sex: Female, Male: Female | Participants | 124 | 123 | 122 | 369 |
| Sex: Female, Male: Male | Participants | 0 | 0 | 0 | 0 |
| Race (NIH/OMB): American Indian or Alaska Native | Participants | 1 | 1 | 1 | 3 |
| Race (NIH/OMB): Asian | Participants | 31 | 31 | 32 | 94 |
| Race (NIH/OMB): Native Hawaiian or Other Pacific Islander | Participants | 0 | 0 | 0 | 0 |
| Race (NIH/OMB): Black or African American | Participants | 3 | 4 | 3 | 10 |
| Race (NIH/OMB): White | Participants | 89 | 85 | 84 | 258 |
| Race (NIH/OMB): More than one race | Participants | 0 | 2 | 2 | 4 |
| Race (NIH/OMB): Unknown or Not Reported | Participants | 0 | 0 | 0 | 0 |
6. Primary Endpoint
The registry lists the primary outcome as Progression Free Survival (PFS) Events in Lapatinib + Trastuzumab + Aromatase Inhibitor (AI) vs. Trastuzumab + Aromatase Inhibitor (AI), measured over From date of randomization until date of progression or date of death from any cause, whichever comes first, assessed up approximately 5 years.
| Element | Registry entry |
|---|---|
| Result type | Count Of Participants |
| Measure of spread | not applicable |
| Unit | Participants |
| Endpoint classification | Binary Endpoint |
Progression-free survival is defined in the registry as the time from randomization until disease progression or death from any cause, whichever occurs first. The stated assessment period extended up to approximately 5 years. The primary outcome is described as a count of participants with such events, based on investigator assessments, rather than as a reported time-to-event estimate in the information available for this analysis.
Generally, progression-free survival is used to capture whether a participant experiences worsening disease or dies before a later assessment. Including death from any cause means that death qualifies as an event even if progression has not been recorded. This can make the endpoint relevant when both disease progression and survival are important aspects of the clinical course. It does not, by itself, describe overall survival, symptom burden or quality of life.
A count of participants with events is not interchangeable with a hazard ratio, median progression-free survival or a time-specific probability of remaining progression-free. Such measures use the timing of events and, in some cases, censoring information. Those results are not reported in the registry record in the registry record for this analysis. The count-based primary outcome also requires its follow-up context to be considered: participants with different observation times may have different opportunities for an event to be recorded. The registry record does not provide the arm-specific counts or follow-up distribution needed to assess that issue.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The registry record identifies a randomized comparison between lapatinib plus trastuzumab plus an aromatase inhibitor and trastuzumab plus an aromatase inhibitor. Its primary outcome is the number of participants with investigator-assessed progression-free survival events. However, the primary event counts, an effect estimate and a confidence interval are not reported in the registry record in the registry record for this analysis. Without these results, the direction, magnitude and precision of the comparison cannot be described.
Enrollment was 369 across the trial, which included three treatment groups. That overall enrollment figure does not establish how many participants were assigned to either group in the primary comparison, how many had evaluable outcome data, or how many experienced an event. The registry defines the primary outcome population as participants in the Intent-to-Treat population with available data for the measure, but does not give the number meeting that description.
Generally, an effect estimate describes the observed contrast between treatment groups, while a confidence interval describes the range of values reasonably compatible with the data under the analysis assumptions. A narrow interval indicates greater statistical precision than a wide interval. Neither an estimate nor an interval is available for the primary comparison in the registry record, so no conclusion about the strength of evidence or statistical uncertainty can be drawn. A p-value alone, even if available, would not communicate the size or clinical importance of an effect; no primary p-value is reported either.
The registry lists secondary outcomes, including overall survival, overall response rate, clinical benefit rate, time to response, duration of response and quality of life. Their names indicate the range of questions considered, but outcome values and comparative estimates for them are not reported in the registry record in the registry record for this analysis. The results therefore cannot be interpreted as a complete assessment of all listed outcomes.
Safety information includes serious adverse event counts for the on-treatment groups and common serious-event terms. These figures describe reported events, not a causal comparison. The fact that a serious event was recorded in a treatment group does not establish that treatment caused it. The registry entries do not specify the statistical comparison, adjustment strategy or uncertainty estimates for safety outcomes. Consequently, the safety counts should be read descriptively and alongside the limits of the available reporting.
Overall, the trial design defines a clinically focused comparison, but the primary efficacy result is not reported in the registry record for this analysis. The record supports description of the question, design and selected safety counts, not a claim that one regimen performed better or worse.
9. Statistical Methods Explained
Randomized parallel-group design
In a randomized trial, assignment is intended to make treatment groups comparable at the start of the study, apart from chance variation. This supports interpretation of between-group differences as treatment-assignment comparisons, provided that follow-up, outcome measurement and analysis are also handled appropriately. A parallel-group design means participants remain assigned to one treatment group rather than crossing through each regimen. The registry identifies this trial as randomized and parallel, but does not report the allocation sequence method, concealment procedures, stratification factors or details of adherence to assigned treatment.
What does open-label mean for assessment?
Open-label indicates that masking was absent. Participants and study personnel could know the assigned regimen. The primary endpoint was based on investigator assessments of progression, so knowledge of assignment could matter for how an assessment is made or timed. This is a general concern in unmasked studies, not evidence that assessment bias occurred in this trial. The registry record does not report whether independent review or other safeguards were used.
What does the primary outcome count?
The primary measure counts participants with a progression-free survival event. The event definition is progression or death from any cause, whichever comes first, measured from randomization. This is a binary outcome for each participant over the defined observation period: an event is recorded or it is not. A count by group can be useful as a straightforward description, but interpretation depends on the size of each group and the length and completeness of follow-up.
As a general statistical point, time-to-event analyses use both event timing and information about participants who have not had an event by the end of observation or who leave observation earlier. Such participants may be censored rather than treated as though they had an event. A time-to-event estimate can therefore answer a different question from a simple event count. Although the endpoint name is progression-free survival and the registry gives a time frame, the registry entries do not report a hazard ratio, median, survival curve, censoring details or event timing.
How should uncertainty be evaluated?
Generally, a confidence interval communicates statistical uncertainty around an estimated effect. Its interpretation depends on the chosen estimand, model and analysis assumptions. A confidence interval that is wide permits a broad range of possible effects; a narrow one indicates greater precision. A p-value evaluates compatibility between the data and a specified null model under the analysis assumptions, but does not show the size of an effect or its importance to participants. The primary effect estimate, confidence interval and p-value are not reported in the registry record in the registry record for this analysis.
The posted sample-size material is described as a planning illustration based on an observed effect, with a two-sided significance level of 0.05, equal allocation between two arms and a normal approximation. For time-to-event outcomes, the illustration uses a total number of events; for other outcomes, it uses participants per arm. These are planning assumptions, not evidence about how the trial was designed. The registry record does not report the trial's own sample-size justification, target effect, planned power or statistical assumptions. Planning illustrations must not be interpreted as observed power or as a substitute for the trial's actual result.
Why does over-dispersion matter?
Generally, over-dispersion occurs when observed variability is greater than a statistical model expects. If a model assumes less variability than the data contain, standard errors can be too small and confidence intervals too narrow, making evidence appear more precise than it is. The primary outcome is a participant event count rather than a repeated count or rate, and the registry entries do not report an over-dispersion assessment or model. No claim about over-dispersion in this trial can therefore be made.
What can be inferred from the safety counts?
Adverse-event counts are descriptive unless the analysis specifies a comparative method and accounts for differences in exposure and follow-up. Participants can experience more than one event, and counts of people affected are distinct from counts of event episodes. The posted safety details use at-risk and affected counts for serious and other adverse events, but do not specify exposure-adjusted rates, statistical comparisons or uncertainty intervals. A count difference should not be converted into a risk ratio or percentage difference without the appropriate analysis, and no such recalculation is made.
The registry reports deaths in both on-treatment and post-treatment groupings. These categories should not be added together or interpreted as treatment-caused deaths without definitions and participant-level context. The registry entries do not report cause of death, timing, attribution or overlap between the categories. In general, safety interpretation requires clear definitions of the observation period, event seriousness, treatment exposure and whether events were considered related to treatment.
10. Multiplicity, Missing Data and Analysis Populations
The trial lists several secondary outcomes in addition to the primary progression-free survival outcome. When multiple outcomes or comparisons are tested, the chance of at least one apparently notable result can increase if no adjustment or prioritization strategy is used. This is the general issue of multiplicity. The registry entries do not report whether a multiplicity adjustment was planned, which secondary outcomes were formally tested, or how the primary and secondary analyses were ordered. These details are not reported in the registry record.
The registry entries identify an Intent-to-Treat population with available data for the primary outcome. They do not report the number of participants included in that population, the extent or pattern of missing outcome data, reasons for missingness, or methods used to address missing data. Generally, missingness can affect an estimate when the likelihood of missing data is related to prognosis or treatment. The available description is not enough to determine whether such bias occurred or how sensitive results were to missing data.
The record also does not report the handling of treatment discontinuation, switching, protocol deviations, or participants who did not adhere to assigned treatment. Nor does it provide details of censoring for the time-to-event definition. These omissions limit assessment of which participants contributed to each analysis and how the analysis handled events or follow-up after treatment changed.
Randomization does not by itself resolve these reporting questions. Transparent outcome-specific analysis populations, missing-data methods and multiplicity procedures are needed to interpret a complete set of results. In their absence, the primary comparison cannot be reconstructed, and conclusions about secondary outcomes or robustness are not supported by these registry entries.
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 |
|---|---|---|---|
| Lapatinib + Trastuzumab + Aromatase Inhibitor (AI) | 27 | 123 | 22.0% |
| Lapatinib + Aromatase Inhibitor (AI) | 23 | 123 | 18.7% |
| Trastuzumab + Aromatase Inhibitor (AI) | 14 | 121 | 11.6% |
Deaths
| Arm | Deaths (participants affected of at risk) |
|---|---|
| Lapatinib + Trastuzumab + Aromatase Inhibitor (AI) | 5 of 124 |
| Lapatinib + Aromatase Inhibitor (AI) | 8 of 123 |
| Trastuzumab + Aromatase Inhibitor (AI) | 5 of 122 |
| Lapatinib + Trastuzumab + Aromatase Inhibitor (AI) (Post-treatment) | 33 of 118 |
| Lapatinib + Aromatase Inhibitor (AI) (Post-treatment) | 37 of 114 |
| Trastuzumab + Aromatase Inhibitor (AI) (Post-treatment) | 34 of 116 |
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 |
|---|---|
| Lapatinib + Trastuzumab + Aromatase Inhibitor (AI) | 113 of 123 |
| Lapatinib + Aromatase Inhibitor (AI) | 107 of 123 |
| Trastuzumab + Aromatase Inhibitor (AI) | 86 of 121 |
| Lapatinib + Trastuzumab + Aromatase Inhibitor (AI) (Post-treatment) | 0 of 0 |
| Lapatinib + Aromatase Inhibitor (AI) (Post-treatment) | 0 of 0 |
| Trastuzumab + Aromatase Inhibitor (AI) (Post-treatment) | 0 of 0 |
Most frequent serious adverse event terms
| Event term | Organ system | Lapatinib + Trastuzumab + Aromatase Inhibitor (AI) | Lapatinib + Aromatase Inhibitor (AI) | Trastuzumab + Aromatase Inhibitor (AI) | Lapatinib + Trastuzumab + Aromatase Inhibitor (AI) (Post-treatment) | Lapatinib + Aromatase Inhibitor (AI) (Post-treatment) | Trastuzumab + Aromatase Inhibitor (AI) (Post-treatment) |
|---|---|---|---|---|---|---|---|
| Ejection fraction decreased | Investigations | 7 of 123 | 1 of 123 | 2 of 121 | n/a of 0 | n/a of 0 | n/a of 0 |
| Cellulitis | Infections and infestations | 3 of 123 | 1 of 123 | 2 of 121 | n/a of 0 | n/a of 0 | n/a of 0 |
| Urinary tract infection | Infections and infestations | 2 of 123 | 0 of 123 | 1 of 121 | n/a of 0 | n/a of 0 | n/a of 0 |
| Cardiac failure | Cardiac disorders | 1 of 123 | 0 of 123 | 1 of 121 | n/a of 0 | n/a of 0 | n/a of 0 |
| Alanine aminotransferase increased | Investigations | 1 of 123 | 1 of 123 | 0 of 121 | n/a of 0 | n/a of 0 | n/a of 0 |
| Hypokalaemia | Metabolism and nutrition disorders | 2 of 123 | 0 of 123 | 0 of 121 | n/a of 0 | n/a of 0 | n/a of 0 |
| Pleural effusion | Respiratory, thoracic and mediastinal disorders | 0 of 123 | 1 of 123 | 1 of 121 | n/a of 0 | n/a of 0 | n/a of 0 |
| Anaemia | Blood and lymphatic system disorders | 1 of 123 | 0 of 123 | 0 of 121 | n/a of 0 | n/a of 0 | n/a of 0 |
| Febrile neutropenia | Blood and lymphatic system disorders | 0 of 123 | 1 of 123 | 0 of 121 | n/a of 0 | n/a of 0 | n/a of 0 |
| Acute myocardial infarction | Cardiac disorders | 0 of 123 | 1 of 123 | 0 of 121 | n/a of 0 | n/a of 0 | n/a of 0 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Lapatinib + Trastuzumab + Aromatase Inhibitor (AI) | Lapatinib + Aromatase Inhibitor (AI) | Trastuzumab + Aromatase Inhibitor (AI) | Lapatinib + Trastuzumab + Aromatase Inhibitor (AI) (Post-treatment) | Lapatinib + Aromatase Inhibitor (AI) (Post-treatment) | Trastuzumab + Aromatase Inhibitor (AI) (Post-treatment) |
|---|---|---|---|---|---|---|---|
| Diarrhoea | Gastrointestinal disorders | 87 of 123 | 64 of 123 | 11 of 121 | n/a of 0 | n/a of 0 | n/a of 0 |
| Rash | Skin and subcutaneous tissue disorders | 43 of 123 | 36 of 123 | 3 of 121 | n/a of 0 | n/a of 0 | n/a of 0 |
| Nausea | Gastrointestinal disorders | 28 of 123 | 28 of 123 | 13 of 121 | n/a of 0 | n/a of 0 | n/a of 0 |
| Paronychia | Infections and infestations | 39 of 123 | 21 of 123 | 0 of 121 | n/a of 0 | n/a of 0 | n/a of 0 |
| Arthralgia | Musculoskeletal and connective tissue disorders | 22 of 123 | 19 of 123 | 15 of 121 | n/a of 0 | n/a of 0 | n/a of 0 |
| Fatigue | General disorders | 15 of 123 | 19 of 123 | 12 of 121 | n/a of 0 | n/a of 0 | n/a of 0 |
| Headache | Nervous system disorders | 9 of 123 | 21 of 123 | 15 of 121 | n/a of 0 | n/a of 0 | n/a of 0 |
| Cough | Respiratory, thoracic and mediastinal disorders | 12 of 123 | 16 of 123 | 17 of 121 | n/a of 0 | n/a of 0 | n/a of 0 |
| Stomatitis | Gastrointestinal disorders | 23 of 123 | 16 of 123 | 5 of 121 | n/a of 0 | n/a of 0 | n/a of 0 |
| Aspartate aminotransferase increased | Investigations | 11 of 123 | 22 of 123 | 11 of 121 | n/a of 0 | n/a of 0 | n/a of 0 |
Serious events with the highest arm-level rate: ejection fraction decreased (5.7%), cellulitis (2.4%), urinary tract infection (1.6%), hypokalaemia (1.6%), cardiac failure (0.8%).
The registry lists serious adverse events for the three on-treatment groups. For lapatinib plus trastuzumab plus an aromatase inhibitor, 27 of 123 participants at risk were affected; for lapatinib plus an aromatase inhibitor, 23 of 123 were affected; and for trastuzumab plus an aromatase inhibitor, 14 of 121 were affected. These are counts of participants, not a comparative estimate adjusted for exposure, follow-up or other factors. The registry entries do not provide confidence intervals or a statistical test for these group comparisons.
Other adverse events affected 113 of 123 participants in the triple-treatment group, 107 of 123 in the lapatinib-plus-aromatase-inhibitor group and 86 of 121 in the trastuzumab-plus-aromatase-inhibitor group. Serious-event terms listed include ejection fraction decreased at 5.7%, cellulitis at 2.4%, urinary tract infection at 1.6%, hypokalaemia at 1.6%, cardiac failure at 0.8% and cardio-respiratory arrest at 0.8%. The registry entries do not clarify the denominators or comparative estimates for these term percentages.
Post-treatment entries separately list deaths, but the registry entries do not report causes or whether deaths were attributed to treatment. These figures should not be interpreted as proof of causation or as directly comparable risks without the relevant definitions and analysis.
12. What the Result Does, and Does Not, Mean
The trial addresses a defined comparative question: progression-free survival events for a regimen combining lapatinib, trastuzumab and an aromatase inhibitor versus trastuzumab plus an aromatase inhibitor in a specified metastatic breast cancer population. Randomized assignment is an important design feature for evaluating treatment groups. The registry also documents a third regimen and several secondary outcomes, as well as selected safety counts.
What the record does not establish in the registry record for this analysis is the primary comparison’s event count, effect size, direction or precision. Without the comparative result and its uncertainty, it is not possible to say whether the groups differed, how large any difference was, or which values remain compatible with the data. The absence of reported results in this account is not evidence that there was no difference.
Generally, a statistically detectable difference and a clinically meaningful difference are distinct ideas. Statistical evidence concerns compatibility with a model and uncertainty; clinical importance depends on the size and consequences of an effect in the relevant population. Neither can be evaluated for the primary outcome without its estimate and context. The listed secondary outcomes likewise cannot be interpreted from their names alone.
The safety counts describe how many participants were recorded as affected in each group, and the listed percentages describe selected serious-event terms. They do not establish that a treatment caused an event or that one regimen has a greater or lower safety risk. A full safety comparison would require event definitions, observation periods, treatment exposure, appropriate denominators and uncertainty estimates.
Accordingly, the supported conclusion is about the study’s design and outcome definitions, not about comparative efficacy or safety. The registry record can frame what the investigators set out to compare, but the outcome results and analysis details needed for stronger interpretation are not reported in the registry record.
13. Why This Trial Matters Statistically
This trial is statistically notable for a clear randomized comparison within a three-group design. The primary contrast compares a regimen containing lapatinib, trastuzumab and an aromatase inhibitor with trastuzumab plus an aromatase inhibitor. A third group received lapatinib plus an aromatase inhibitor. Distinguishing the primary contrast from the broader set of treatment groups and outcomes is important when interpreting trial results.
The endpoint also illustrates why outcome definition matters. Progression-free survival combines disease progression and death from any cause, while the recorded primary measure is described as the number of participants with events. Event counts are readily understandable, but they do not convey event timing in the same way as time-to-event estimates. Interpretation therefore depends on follow-up and censoring details, which are not reported in the registry record for this analysis.
Open-label treatment assignment and investigator assessment are relevant statistical considerations. They do not invalidate a randomized design, but they make reporting of assessment procedures and analysis methods especially useful. The registry entries do not describe those procedures or supply the comparative efficacy result. This creates a distinction between a well-defined research question and a result that can be independently interpreted from the recorded information.
Finally, the study lists multiple secondary outcomes and reports selected safety counts. This highlights the need to distinguish descriptive results from prespecified confirmatory comparisons, and to account for multiple testing where appropriate. The registry record does not report the multiplicity strategy. Together, these features show why design labels alone are insufficient: endpoint details, analysis populations, missing-data handling, uncertainty and outcome reporting all shape what a trial can support.
14. Limitations
- The posted summary statistics are the only data these results rest on; patient-level data, full protocols and statistical analysis plans are not available.
- Recalculated results are simple, unadjusted calculations from posted summaries. They do not replace the sponsor's prespecified analysis.
The primary limitation for interpreting efficacy is that the primary outcome counts and comparative estimates are not reported in the registry record for this analysis. The registry description names progression-free survival events and defines the assessment period, but it does not give the number of events by group, an effect estimate, a confidence interval or a p-value. The comparative result therefore cannot be assessed for direction, magnitude or precision.
The trial enrolled 369 participants across three treatment groups, but the registry entries do not give the actual randomized number in each group or the number analyzed for the primary outcome. The outcome population is described as the Intent-to-Treat population with available data, but missingness and exclusions are not detailed. Follow-up distribution, censoring, adherence and treatment changes are likewise not described.
The primary outcome relied on investigator assessment in an open-label trial. The registry entries do not describe independent review, assessment safeguards or the methods used to limit bias. They also do not report the statistical analysis plan, sample-size justification, allocation procedures, multiplicity strategy or sensitivity analyses. These omissions prevent assessment of whether the analysis followed prespecified methods and how robust the findings were.
Safety reporting is also limited. Counts are available for participants affected by serious and other adverse events, and selected serious-event terms have percentages, but exposure duration, event attribution, denominator definitions and comparative uncertainty are not reported in the registry record. Post-treatment deaths are listed without causes or other context. These data support description only, not causal attribution or adjusted comparisons.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: A Study to Compare the Safety and Efficacy of an Aromatase Inhibitor in Combination With Lapatinib, Trastuzumab or Both for the Treatment of Hormone Receptor Positive, HER2+ Metastatic Breast Cancer — NCT01160211.
- Registry record last updated 2025-03-07; status last verified 2025-03.
- Results first posted 2019-07-15.
- 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
NCT01160211 is a completed randomized, open-label, parallel-group Phase III study sponsored by Novartis Pharmaceuticals. It enrolled 369 participants with hormone receptor-positive, HER2-positive metastatic breast cancer and compared three aromatase-inhibitor combinations involving lapatinib, trastuzumab or both. The primary comparison was lapatinib plus trastuzumab plus an aromatase inhibitor versus trastuzumab plus an aromatase inhibitor.
The primary outcome was the number of participants with investigator-assessed progression-free survival events, defined as progression or death from any cause from randomization through assessment up to approximately 5 years. Secondary outcomes included overall survival, response measures, response timing and duration, and quality of life. The primary comparison’s outcome values and statistical estimate are not reported in the registry record for this analysis. Serious and other adverse-event counts are listed, but the information does not establish comparative causation or risk.