Phase II Open-Label Trial of Tarceva in Women With Metastatic, Hormone- and HER2-Negative Breast Cancer: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Phase II Open-Label Trial of Tarceva in Women With Metastatic, Hormone- and HER2-Negative Breast Cancer (NCT00597597), a na phase 2 study. The primary outcome is The Primary Objective of the Study is Progression Free Survival..

2. Clinical Question

The clinical question is whether erlotinib has activity in a biologically selected group of women with metastatic breast cancer. The selection rationale focuses on tumors positive for EGFR while lacking hormone receptors and HER2/neu. This identifies the population the investigators intended to study; it does not establish that every participant had all of these markers documented in the posted results.

The trial also listed secondary outcomes concerning objective response under RECIST criteria, clinical benefit including stable disease for 6 months, duration of objective response, safety, and participants with rash. These outcomes address tumor response and tolerability alongside the primary time-to-event objective. The registry record does not report numerical results for these outcomes. In particular, the stated objective and outcome definitions should not be mistaken for evidence that a response or clinical benefit was observed.

Because the study has no control arm, its clinical question is descriptive rather than a direct comparison of erlotinib with another treatment or with usual care. Any interpretation must therefore distinguish the intended question of activity in this selected population from a causal claim that treatment changed outcomes.

3. Trial Design

This was a Phase II, open-label, single-group trial sponsored by Rush University Medical Center. The registry lists enrollment of 11 and describes the intervention as erlotinib. All enrolled subjects in the arm description received active drug. Masking was listed as none, and allocation was not applicable. The study therefore has no randomized comparator arm against which to estimate a treatment contrast.

The trial title identifies women with metastatic, hormone- and HER2-negative breast cancer. The brief description gives a more specific selection rationale: ER-negative, PR-negative, HER2/neu-negative, EGFR-positive breast cancer. The record does not report additional eligibility details such as how each biomarker was measured, the precise thresholds used, or what prior treatments were permitted.

The primary objective was progression-free survival from the day of initial treatment until documented progression or death. The stated assessment timeframe was up to 6 months. Secondary outcomes included complete and partial responses according to RECIST criteria, clinical benefit defined to include stable disease for 6 months, duration of objective response, safety, and the number of participants with rash. The record lists 6 outcome measures and 0 analyses.

The registry lists a start date of 2007-04, a primary completion date of 2011-04, and a terminated status. It does not report why the trial was terminated, whether the termination changed the planned analyses, or whether follow-up continued after the primary completion date. The enrollment figure describes the recorded trial enrollment; the record does not explain how many participants contributed evaluable data to each outcome.

With no concurrent control group, observed outcomes would be interpreted as experience among participants receiving erlotinib, not as a randomized estimate of the effect of erlotinib relative to another treatment. The registry record does not report a planned statistical analysis sufficient to clarify how the investigators intended to address the limitations of a small single-group study.

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

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.

6. Primary Endpoint

The registry lists the primary outcome as The Primary Objective of the Study is Progression Free Survival., measured over From the Day of Initial Treatment (Day 0) Until Documented Disease Progression or Death, whichever came first, assessed up to 6 months..

Progression-free survival measures the time from initial treatment until the first of documented disease progression or death. It combines these events into a time-to-event outcome. The registry describes the primary objective as progression-free survival and specifies that follow-up for this outcome begins on the day of initial treatment, identified as Day 0. The assessment timeframe is stated as up to 6 months.

Time-to-event outcomes are useful when the timing of an event matters and when participants may have different lengths of observation. In general, the analysis can account for participants who have not had the event by the end of their observed follow-up, provided that suitable follow-up and censoring information are available. The registry record does not report how censoring was handled, the details of event confirmation, or the analysis population used.

The listed parameter is the median, with standard deviation named as the dispersion measure. The record does not provide a median progression-free survival estimate, its uncertainty, or an event count for this endpoint. It therefore supports describing the outcome definition and the intended follow-up, but not the observed progression-free survival experience.

Progression-free survival is used as an outcome because it captures either documented worsening of disease or death, rather than response alone. It is not interchangeable with overall survival, tumor response, or clinical benefit. Those outcomes were listed separately in the registry. No numerical result for any of them is reported in the record, so the endpoint definition alone cannot establish the size or precision of an observed treatment-associated outcome.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

Several statistical ideas help distinguish what this trial was designed to measure from what the registry record actually reports. The outcome definition, study design, and available results answer different questions: the definition says what counts as an event, the design says what comparisons are possible, and the posted results show what was estimated. In this record, the first two are described more fully than the numerical efficacy findings.

What does a time-to-event endpoint represent?

Progression-free survival is a time-to-event outcome. Each participant contributes follow-up from the stated starting point until progression or death, whichever occurs first. In general, time-to-event methods are useful because they preserve information about when events occur, rather than reducing every observation to a simple event-or-no-event status. They can also accommodate participants whose event has not been observed by the end of their available follow-up, through censoring methods.

Censoring does not mean that an event did not happen; it means that the event time is not known beyond the last observed follow-up. Valid analysis depends on knowing how follow-up ended and applying assumptions appropriate to the censoring process. The registry record does not report the censoring rules, follow-up completeness, or event counts for progression-free survival. Without those details and a reported estimate, the endpoint cannot be reconstructed from the registry information.

What does a median mean?

A median time-to-event estimate describes a central point in the distribution of event times. It is not the same as an average duration, and it does not describe every participant’s outcome. The record specifies a median as the parameter of interest and names standard deviation as dispersion, but it does not provide the estimated median or a measure of uncertainty around it. A dispersion label without the associated estimate does not permit an assessment of precision.

Why does the single-group design matter?

In a randomized comparison, treatment groups can be compared under a design intended to balance prognostic factors. This trial instead has a single group receiving active erlotinib, with no masking and no comparator. General descriptions of outcomes in that group would not by themselves separate treatment effects from disease course, participant selection, concurrent care, or other influences. A within-group outcome is not equivalent to a controlled estimate of what would have happened without erlotinib.

Open-label status means the record does not describe masking of participants or investigators. For objectively defined events, this may be less consequential than for outcomes involving judgment or reporting, but assessment procedures still matter. The record does not explain how progression was assessed, whether review was independent, or how potential assessment bias was managed.

How should hazard ratios and confidence intervals be read?

A hazard ratio is a relative measure comparing event rates over follow-up under a specified model. In general, it summarizes a comparison between groups; it is not a median survival time and does not state an individual participant’s probability of an event. Since this study is recorded as single-group and no analyses are listed, the registry record does not report a hazard ratio for a treatment comparison.

A confidence interval communicates statistical uncertainty around an estimate: narrower intervals indicate greater precision, while wider intervals indicate less precision. It is not a guarantee that the true value lies within the interval. No confidence interval for progression-free survival is reported in the registry record. Therefore, readers cannot assess the primary endpoint’s precision from the posted information.

What do the planning assumptions describe?

The planning illustration is described as based on the observed effect, with a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. It says the effect to detect is a stated fraction of the observed effect. For time-to-event outcomes, the illustration is based on the total number of events using the Schoenfeld approach; other outcomes are expressed as participants per arm.

These assumptions describe planning calculations, not findings from the trial. Equal allocation between two arms is not the design recorded for this study, which has one group and no allocation to a comparator. The illustration should therefore not be interpreted as the actual trial’s design or as evidence of observed power. The registry record does not report a trial-specific sample-size justification, and no numerical planning results are stated in the available record.

More broadly, power is a design concept that depends on assumptions about the effect, variability, event occurrence, and analysis. A calculation based on an observed effect is not a measurement of the study’s realized ability to detect an effect. This distinction matters especially when the underlying efficacy result and its uncertainty are not reported.

10. Multiplicity, Missing Data and Analysis Populations

The registry lists multiple outcomes: progression-free survival as the primary objective, along with secondary measures concerning RECIST response, clinical benefit, duration of objective response, safety, and rash. Considering multiple outcomes raises the general issue of multiplicity: when many hypotheses or endpoints are examined, the chance of at least one apparently notable result can increase unless the analysis plan addresses that issue. The registry record does not report a multiplicity adjustment or a prespecified hierarchy for interpreting the outcomes.

The record lists 6 outcome measures and 0 analyses. It does not provide outcome-specific numerical efficacy results, confidence intervals, or p-values. It also does not report whether any analyses were planned but not posted, whether outcomes changed over time, or how missing observations were handled. These details are not reported in the registry record; their absence should not be filled by assuming a particular analysis strategy.

Analysis populations are also not described. The registry record does not state how many participants were included in the progression-free survival analysis, whether all enrolled participants were analyzed, or how exclusions and withdrawals were treated. The recorded enrollment of 11 should not be assumed to be the denominator for every endpoint.

For a time-to-event outcome, incomplete follow-up and censoring can affect both the estimate and its precision. For response outcomes, missing assessments can affect the denominator and classification. General approaches depend on the reasons data are missing and on the endpoint definition; no specific missing-data method is reported in the registry record. Without these details, the completeness and analysis basis of the unreported efficacy outcomes cannot be assessed.

11. Safety Results

The registry reports serious adverse events as affected participants divided by participants at risk.

Deaths

Other (non-serious) adverse events

Participants with at least one non-serious event at or above the registry's 0% reporting threshold.

Most frequent serious adverse event terms

Serious events with the highest arm-level rate: diarrhea (18.2%), rash (9.1%), nausea (9.1%), weight loss (9.1%).

The registry’s adverse-event grouping reports 11 at risk for serious events and 11 at risk for other events. The serious-event field records 2 affected, while the other-event field records 0 affected. The same grouping records 11 deaths. These are separate entries in the registry summary and should not be combined or interpreted as a causal account without further detail.

The listed serious adverse-event terms are diarrhea (18.2%), rash (9.1%), nausea (9.1%), and weight loss (9.1%). The registry record does not explain the denominator used for these percentages, whether a person could contribute more than one event term, or the event grades and timing. The listed percentages therefore should not be converted into participant counts or treated as rates with a known exposure-time basis.

A reported death count does not establish that deaths were caused by the study drug. The record does not provide attribution, timing, cause of death, or a comparison group. Nor does a zero in the other-event field mean that no adverse experiences occurred outside the reported category; it describes only that registry field. These figures are a limited safety summary, not a complete characterization of risks or a comparative safety analysis.

12. What the Result Does, and Does Not, Mean

The registry record establishes that investigators conducted an open-label Phase II study of erlotinib in a selected population of women with metastatic, hormone receptor-negative and HER2-negative breast cancer. It identifies progression-free survival as the primary objective and defines the event as documented progression or death. It also lists several secondary measures related to response, clinical benefit, duration, and safety.

The record does not report the median progression-free survival or numerical efficacy results for the secondary outcomes. It therefore does not establish the observed level of tumor response, the duration of any response, or the amount of time participants remained progression-free. The trial’s stated purpose and biomarker-based rationale should not be confused with evidence that erlotinib produced a particular outcome.

The design also does not support a direct treatment-versus-control comparison. All participants in the listed arm received active drug, and the study had no concurrent comparator. Even if a numerical within-group outcome were available, it would describe observed experience in that group and would not, by itself, establish what would have occurred under another treatment or without erlotinib.

The adverse-event summary provides limited counts and event terms but does not establish causation, comparative safety, or the full frequency and severity of adverse experiences. The listed deaths should not be attributed to treatment on the basis of these figures alone.

These limitations do not make the registry record uninformative: it conveys the question, population, design, intended outcomes, status, and selected safety information. They do mean that efficacy conclusions and their precision cannot be drawn from the posted results described in the record. The reason for termination, missing-data procedures, analysis populations, and trial-specific statistical plan are not reported in the registry record.

13. Why This Trial Matters Statistically

This trial illustrates why a clearly stated clinical objective and an interpretable numerical result are both needed for statistical assessment. The registry identifies progression-free survival as the primary objective and defines when follow-up begins and what event ends it. Those details make the intended endpoint understandable. However, the median estimate and its uncertainty are not reported, so the endpoint’s observed value and precision cannot be evaluated.

The study also demonstrates the distinction between a biologically selected population and a controlled treatment comparison. Selecting participants based on hormone receptor, HER2/neu, and EGFR status can make a research question more specific. It does not remove the limitations of a single-group design. Without a concurrent comparator, observed outcomes cannot isolate the effect of erlotinib from other influences.

Multiplicity and missingness matter when several outcomes are listed. Response, clinical benefit, duration, and safety answer different questions, and each depends on suitable definitions, denominators, and analysis methods. The registry record lists multiple outcome measures but reports 0 analyses and does not describe adjustments for multiple testing or methods for missing data. These omissions make it difficult to understand how results would have been selected and interpreted.

Finally, planning calculations must be read in the context of the design they assume. The described illustration assumes equal allocation between two arms, whereas the recorded trial has one group. It is a planning framework, not observed power and not a substitute for a reported outcome. Together, these features show why registry completeness, design alignment, and clear reporting of estimates and uncertainty are central to clinical-trial 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 trial-specific limitation is the absence of reported numerical results for the primary endpoint. Although the record defines progression-free survival and specifies a median, it does not report an estimate, uncertainty interval, or event count. The record also lists 0 analyses, limiting statistical interpretation beyond the design and outcome definitions.

The single-group, open-label design has no concurrent control. It can describe outcomes among participants who received erlotinib if those outcomes are reported, but it cannot provide a randomized estimate of treatment effect relative to another option. The record does not describe an external comparator or a method for adjusting comparisons with other data.

Enrollment was 11, and the trial status is terminated. The registry record does not report why it was terminated, whether the intended enrollment was reached, whether outcome follow-up was complete, or how termination affected the planned analysis. It also does not specify analysis populations, participant flow, censoring procedures, handling of missing data, or the methods used to assess progression.

The population description gives the biomarker rationale but does not report detailed eligibility criteria or how marker status was established. The adverse-event summary lacks explanatory detail about percentage denominators, event grading, timing, and attribution. Its figures therefore cannot be used as a complete or comparative safety assessment.

Finally, the stated planning assumptions concern a two-arm design, while the recorded study is single-group. No trial-specific sample-size justification or statistical analysis plan is reported in the registry record. These limitations leave the primary efficacy outcome, its precision, and the reasons for the study’s status unresolved.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Phase II Open-Label Trial of Tarceva in Women With Metastatic, Hormone- and HER2-Negative Breast Cancer — NCT00597597.
• Registry record last updated 2023-05-17; status last verified 2023-05.
• Results first posted 2023-05-17.
• 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.

18. Record Summary

This Phase II study evaluated open-label erlotinib in women with metastatic, hormone receptor-negative and HER2-negative breast cancer. The stated rationale focused on ER-negative, PR-negative, HER2/neu-negative, EGFR-positive disease. The study was single-group, had no masking or comparator, and recorded enrollment of 11. Rush University Medical Center was the sponsor.

Progression-free survival was the primary objective, defined from initial treatment until documented progression or death, whichever came first, with assessment up to 6 months. The registry also lists response, clinical benefit, duration of objective response, safety, and rash outcomes. It records 6 outcome measures and 0 analyses, but does not report a numerical primary endpoint result.

The record lists a start date of 2007-04, a primary completion date of 2011-04, and a terminated status. It includes a limited adverse-event summary, but does not report why the trial was terminated, the statistical plan, analysis populations, or missing-data methods.