Erlotinib Plus Docetaxel in Treating Patients With Stage IV or Recurrent Breast Cancer: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Erlotinib Plus Docetaxel in Treating Patients With Stage IV or Recurrent Breast Cancer (NCT00054275), a na phase 2 study. The primary outcome is Disease Response (Tumor Measurements)Per RECIST Criteria v. 2000.

2. Clinical Question

The trial was registered as a phase II study of treatment for recurrent and/or metastatic breast cancer. Its stated rationale was that erlotinib may block enzymes involved in tumor-cell growth and that combining it with chemotherapy might affect tumor-cell division. Those statements describe the study rationale, not a finding from the clinical results. The available record identifies progression-free survival and overall survival as secondary outcomes, but does not provide their estimates or event counts.

3. Trial Design

This was a phase II, single-group study of erlotinib plus docetaxel. The registry record lists 39 participants enrolled and identifies breast cancer as the condition. Its title and description concern patients with stage IV or recurrent breast cancer. The sponsor is listed as Paula Silverman, MD. The study status is completed, with a start date of 2002-12 and primary completion recorded as 2010-04.

The record lists no random allocation and no masking. Because participants were not assigned to a separate comparison group, the design is not a randomized comparison. Outcomes can be described for the treated group, but the design does not isolate the contribution of either drug or determine how the same participants would have fared under another treatment. Differences from other studies or historical experience would not create a concurrent control group.

The intervention is described as weekly docetaxel combined with erlotinib hydrochloride, identified in the official title as OSI-774. The arm is named Erlotinib Plus Docetaxel. The arm description field contains no additional details. Doses, schedules for erlotinib, dose adjustments, treatment duration beyond the primary endpoint timeframe, and rules for stopping treatment are not reported in the registry record.

The primary outcome is disease response based on tumor measurements under RECIST criteria, assessed after 6 course (6 months) of combination therapy. Progression-free survival and overall survival are named as secondary outcomes; the record labels overall survival as of 2008. Their measurement details and results are not reported in the registry record. The registry record also does not report the protocol’s sample-size justification, planned statistical analysis, or whether the study used interim analyses.

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

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: Excluding 11 not evaluable cases

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 Disease Response (Tumor Measurements)Per RECIST Criteria v. 2000, measured over after 6 course (6 months) of combination therapy.

The primary endpoint is disease response assessed from tumor measurements according to the Response Evaluation Criteria in Solid Tumors, or RECIST, version 2000. The registry describes the measure as a number of participants and gives the assessment timeframe as after 6 course (6 months) of combination therapy. The stated population excludes 11 cases that were not evaluable.

RECIST uses changes in the sum of the longest diameters of target lesions. In the registry description, partial response requires at least a 30% decrease in that sum. Progressive disease requires at least a 20% increase. Stable disease means neither sufficient shrinkage nor sufficient increase. These categories translate tumor measurements into a defined response classification rather than relying only on an impression that a tumor has changed.

Such criteria are useful in clinical research because a prespecified measurement rule makes response classification more consistent and interpretable. They do not, by themselves, establish how long a response lasts, whether symptoms change, or how outcomes compare with another treatment. The record does not state the number of participants in each response category, the number classified as having an overall response, or an uncertainty interval. Therefore, the endpoint definition is available, but the primary response result is not reported in the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

Clinical-trial methods are easiest to interpret by separating the question being asked, the way outcomes are measured, and the analysis used to summarize them. In this study, the primary question concerns tumor response after a specified treatment period. The registry identifies a count of participants as the measure and describes the response rules using RECIST. It does not report the response counts or the statistical model used for an inferential analysis.

What does a single-group design estimate?

In a single-group study, participants receive the study intervention and outcomes are described within that group. The design can document what happened among participants who received the regimen, subject to the quality and completeness of outcome measurement. It does not produce a concurrent estimate of outcomes under a different treatment. A comparison with another group would require additional data and assumptions, and would not have the protection against confounding that random assignment is intended to provide.

Here, the registry lists no random allocation and one treatment arm. The study’s results therefore cannot identify the separate contribution of erlotinib or docetaxel. Nor can the observed course of illness among participants, by itself, show what would have occurred to those same participants under an alternative approach. This is a design limitation, not a flaw that can be repaired by a different statistical test.

How does RECIST turn measurements into categories?

RECIST supplies a rule for classifying change in target lesions. The registry description bases the assessment on the sum of the longest diameters. It defines partial response as at least a 30% decrease, progressive disease as at least a 20% increase, and stable disease as neither sufficient shrinkage nor sufficient increase. Applying a shared rule can reduce ambiguity about what counts as response or progression.

Those categories depend on the availability and quality of tumor measurements. A participant without an evaluable assessment cannot be placed reliably into a response category using the described endpoint. The registry states that the primary outcome population excludes 11 not-evaluable cases, but does not report why they were not evaluable, whether they had a baseline assessment, or how their outcomes were treated in any other analysis.

What would an uncertainty interval communicate?

In general, a confidence interval describes the statistical uncertainty around an estimate under a specified analysis and its assumptions. For a response proportion, it would show a range of values reasonably compatible with the observed data and method. It does not correct for the absence of a control group, incomplete outcome measurement, or bias in who is included. No response estimate or confidence interval is reported in the registry record, so neither the observed response level nor its precision can be assessed.

For time-to-event outcomes such as progression-free survival or overall survival, general statistical methods account for the timing of events and the fact that some participants may not yet have had an event at the time of analysis. The treatment of those participants depends on censoring rules and follow-up. The registry lists progression-free survival and overall survival as secondary outcomes, but does not report estimates, event counts, analysis methods, censoring rules, or follow-up details. It is therefore not possible to explain a particular time-to-event estimate from this record.

Why can over-dispersion matter?

As a general statistical point, over-dispersion occurs when observed variability is greater than a model assumes. If a count model assumes less variability than the data contain, standard errors can be too small and uncertainty can appear less than it is. A model that allows extra variability may be more appropriate for some clustered or heterogeneous data. The primary outcome in this record is described as participant counts, but no count model or dispersion estimate is reported. There is no basis in the registry record to say that over-dispersion was assessed or that a particular adjustment was used.

What do planning illustrations mean?

Sample-size planning is distinct from reporting the results of an enrolled study. A planning illustration based on an observed effect is not the trial’s original design justification and is not observed power. The stated illustration assumptions use a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation, with the effect to detect defined as a stated fraction of the observed effect. Those assumptions describe a hypothetical two-arm planning exercise, whereas this trial is single group. The registry record does not report its own sample-size justification. The planning assumptions do not transform this study into a randomized comparison or supply missing outcome results.

In general, a significance level sets a threshold for a statistical test under its assumptions; it does not measure the probability that a treatment works. Power is a design-stage probability of detecting a specified effect if that effect and the model assumptions hold. A planning count is not evidence that an enrolled study had that power, and it cannot substitute for an estimate with its uncertainty. No study-specific significance tests, confidence intervals, or statistical analysis plan are reported in the registry record.

10. Multiplicity, Missing Data and Analysis Populations

The registry lists one primary outcome, disease response by RECIST, and names progression-free survival and overall survival as secondary outcomes. It also records three outcome measures and one analysis. The registry record does not report a multiplicity strategy, such as a rule for controlling false-positive findings across several outcomes or analyses. Without an analysis plan and the corresponding results, it is not possible to determine whether any adjustment was intended or applied.

In general, testing several outcomes can increase the chance that at least one result appears notable by chance. A prespecified hierarchy, adjustment procedure, or clear distinction between confirmatory and exploratory outcomes can help readers understand how to interpret multiple tests. The outcome labels alone do not establish which analyses were confirmatory or how results were selected for reporting.

Missing outcome information is especially relevant to the primary endpoint: the registry describes the response population as excluding 11 cases that were not evaluable. Reasons for missing or non-evaluable assessments, the handling of those participants, and any sensitivity analyses are not reported in the registry record. No imputation method or alternative analysis population is described. The enrollment count is 39, but the record does not give a complete accounting of all participants by assessment status or explain whether all enrolled participants began treatment.

These omissions limit interpretation of both the response estimate and its representativeness. They do not show that a particular method was or was not used outside the registry record; they mean that the method is not reported in the registry record.

11. Safety Results

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

Other (non-serious) adverse events

Participants with at least one non-serious event at or above the registry's 5% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: lymphopenia (35.9%), diarrhea (17.9%), fatigue (15.4%), anorexia (12.8%), leukopenia (10.3%).

The adverse-event summary lists 39 participants at risk for serious adverse events and 28 participants affected. For other adverse events, it lists 39 at risk and 39 affected. These are descriptive counts within the Docetaxel and OSI-774 group. The record does not include a comparator group, so these figures do not provide a relative-risk estimate or a between-treatment comparison.

The serious adverse event terms with the highest listed percentages are lymphopenia at 35.9%, diarrhea at 17.9%, fatigue at 15.4%, anorexia at 12.8%, leukopenia at 10.3%, and neutropenia at 10.3%. The registry record presents these as percentages, but does not provide further detail about event severity grades, timing, duration, recurrence, or how relatedness to treatment was assessed. These percentages should be read as recorded safety summaries, not as proof that treatment caused each event.

The deaths field is not populated in the adverse-event summary, so deaths are not reported in the registry record. The summary also does not provide a complete account of all event types or treatment exposure. Safety interpretation is therefore limited to the listed counts and terms, without a comparative estimate or detailed clinical context.

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

The record establishes that a phase II single-group study enrolled 39 participants to receive erlotinib with docetaxel for recurrent or metastatic breast cancer. It specifies a primary tumor-response endpoint based on RECIST and gives the assessment timeframe as after 6 course (6 months) of combination therapy. It also identifies progression-free survival and overall survival as secondary outcomes. These details clarify the study question and the intended outcome measures.

The record does not report the primary response count, response categories, response proportion, confidence interval, or secondary survival estimates. Consequently, it does not allow a reader to quantify the observed tumor response, its precision, or the duration of outcomes. A defined measurement rule is not a substitute for outcome data. The absence of those results from the registry record should not be interpreted as evidence that no responses or events occurred.

The single-group design also limits what any outcome estimate could establish. A result among participants receiving the combination would describe that group, but would not reveal how outcomes compare with a different treatment in a concurrent control group. It would not show which drug contributed to an outcome or distinguish treatment effects from other explanations. No claim that the regimen works or does not work follows from the information.

The safety summary records serious adverse events among participants and lists several serious-event terms with percentages. These figures provide a descriptive account, but no control group is available for a comparative safety assessment. The registry record does not report deaths in that summary, or the detailed context needed to interpret event timing, severity grades, and attribution.

In short, the posted record supports an understanding of the trial’s structure, endpoint definitions, and certain recorded safety figures. It does not provide enough outcome information to assess the primary response result or the secondary survival outcomes, and the study design does not support a controlled treatment comparison.

13. Why This Trial Matters Statistically

This study illustrates why endpoint definitions and study design need to be read together. RECIST provides explicit criteria for classifying tumor measurements, which makes the intended response outcome understandable. But a precise endpoint definition cannot tell readers what the observed result was when response counts and uncertainty estimates are not reported.

The single-group design is also central to the interpretation. The study can describe outcomes among participants receiving erlotinib plus docetaxel, but has no concurrent control group and no random allocation. That distinction matters whenever the question is comparative: a within-group description is not an estimate of the difference between treatments. A combination regimen also makes it impossible to attribute an observed outcome separately to either drug.

The record further demonstrates the importance of accounting for evaluability. It says the primary outcome excludes 11 cases that were not evaluable, yet does not explain why or how the missing assessments were handled. Reporting the reasons, analysis population, and sensitivity analyses would help readers judge how representative the classified outcomes are of all enrolled participants.

Finally, registering secondary survival outcomes without reporting their estimates leaves important questions unanswered. Progression-free survival and overall survival require information about event counts, follow-up, and analysis methods to support interpretation. The study’s value as a statistical example lies in distinguishing a clearly described measurement framework from complete reporting of results and comparative evidence.

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 principal limitation in the registry record is that it does not report the primary response result. Although the RECIST categories and assessment timeframe are described, response counts and an uncertainty estimate are absent. The registry also lists progression-free survival and overall survival as secondary outcomes without reporting their estimates or event counts.

The single-group design has no randomized or concurrent control arm. Therefore, outcomes cannot be directly contrasted with outcomes under another treatment, and the effects of the two drugs cannot be separated. The record does not report allocation details beyond noting no random allocation, and it provides no blinding because masking is listed as none.

The primary outcome population excludes 11 cases as not evaluable. The record does not explain why they were not evaluable, how many had missing assessments for particular reasons, or what methods were used to handle missing data. The extent to which this affects interpretation cannot be assessed from the posted information.

Additional protocol and analysis details are not reported in the registry record, including the sample-size justification, statistical analysis plan, interim analyses, outcome-analysis methods, and detailed follow-up procedures. The adverse-event summary gives counts and selected serious-event terms but not event timing, severity grades, duration, or attribution details. These limits constrain interpretation of efficacy, precision, missingness, and safety; they do not establish what analyses or procedures may have been used outside the registry record.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Erlotinib Plus Docetaxel in Treating Patients With Stage IV or Recurrent Breast Cancer — NCT00054275.
• Registry record last updated 2016-02-17; status last verified 2016-02.
• Results first posted 2012-03-13.
• 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

NCT00054275 is a completed phase II, single-group study of erlotinib hydrochloride with docetaxel for recurrent and/or metastatic breast cancer. The registry lists 39 participants enrolled, no random allocation, and no masking. The study began in 2002-12, with primary completion recorded as 2010-04.

The primary outcome is disease response by RECIST after 6 course (6 months) of combination therapy. Its stated analysis population excludes 11 not-evaluable cases. Progression-free survival and overall survival are listed as secondary outcomes. The registry record does not report the primary response result or secondary survival estimates. It records serious adverse events in 28 of 39 participants and lists serious-event terms with percentages, but does not report deaths in the adverse-event summary.