Combination Chemotherapy With or Without Trastuzumab Followed By an Autologous Stem Cell Transplant and Radiation Therapy in Treating Patients With Stage III or Stage IV Breast Cancer: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Combination Chemotherapy With or Without Trastuzumab Followed By an Autologous Stem Cell Transplant and Radiation Therapy in Treating Patients With Stage III or Stage IV Breast Cancer (NCT00182793), a non-randomized phase 2 study. The primary outcome is 5-Year Relapse-free Survival Rate.

2. Clinical Question

The question was whether this intensive treatment approach could be evaluated in patients with advanced breast cancer, including a regimen with or without trastuzumab. The posted description does not support a direct causal comparison between regimens: allocation was non-randomized, and the arm descriptions do not fully specify which patients received each treatment sequence. The study therefore needs to be read as a phase II investigation rather than as a randomized test of the separate treatment components.

The endpoint definition combines recurrence and death in the event framework, and treats disease progression as the relevant event for stage IV disease. The registry says the endpoint was estimated by the Kaplan-Meier product-limit method. It also states that patients from this study were combined with patients from a follow-up study, and that 27 participants from this study met eligibility requirements for that meta-analysis. The record does not provide the resulting estimate, number of events, or confidence interval, so the primary question cannot be answered quantitatively from the registry results.

3. Trial Design

This was a phase II, parallel-arm study with non-randomized allocation and no masking. The registry records enrollment of 32 and labels the study completed. The recorded start is 2005-07, and primary completion is recorded as 2014-10. City of Hope Medical Center is listed as the sponsor. These details identify the study structure and record status; they do not establish how participants were assigned to treatment or whether all enrolled participants received the same sequence of therapies.

The overall treatment strategy involved intensive combination chemotherapy, autologous stem cell transplantation, and radiation therapy. Trastuzumab was included in the study purpose and in the description of one arm as an option with melphalan. The registry also lists carboplatin, cyclophosphamide, melphalan, and thiotepa, along with procedures for stem cell collection, transplantation, bone marrow ablation with stem cell support, and adjuvant therapy. The posted arm descriptions are truncated. Details beyond the text recorded for each arm are not reported in the registry record.

The two arms were presented in parallel, but non-randomized allocation means that participants were not assigned by randomization according to the record. Differences between groups could therefore reflect participant characteristics or treatment selection as well as treatment differences. The registry explicitly cautions that the arms are not a like-for-like control comparison. No assumption of baseline balance or causal treatment effect is justified from these design details.

The primary endpoint was a 5-year relapse-free survival rate. Its description defines follow-up from initial peripheral blood progenitor cell rescue to death or disease recurrence, with disease progression applying to stage IV disease, and specifies the Kaplan-Meier product-limit method. The population description adds an important qualification: patients from this study were combined with patients from a follow-up study, with 27 patients from this study meeting eligibility requirements for meta-analysis. The registry does not report the numerical primary endpoint result, the number of events, or the confidence interval. It also does not report the protocol’s rationale for the enrollment target, detailed eligibility criteria, or a complete account of the treatment sequence.

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

Analysis population for the primary outcome, as defined in the registry: Patients from this study were combined with patients from a follow-up study in which 27 patients from this study met the eligibility requirements for meta-analysis.

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 5-Year Relapse-free Survival Rate, measured over From time of initial PBPC rescue until death or disease recurrence (disease progression for patients with stage IV disease), whichever came first, up to 5 years post treatment.

The primary endpoint is named the 5-Year Relapse-free Survival Rate. It concerns the time from initial peripheral blood progenitor cell rescue until death or disease recurrence; for patients with stage IV disease, disease progression is specified as the event. The description says relapse means the appearance of any new lesions during or after protocol treatment and that relapses should be documented histologically whenever possible.

Time-to-event endpoints are useful when the timing of an event matters and participants may have different lengths of follow-up. The Kaplan-Meier product-limit method estimates the probability of remaining event-free over time while accounting for participants whose follow-up ends before an event is observed. This is a general explanation of the method, not a claim about the study’s unreported follow-up patterns.

The registry identifies the endpoint as a 5-year rate and specifies Kaplan-Meier estimation. Its measure metadata labels the parameter as a median and the dispersion as a 95% confidence interval. The actual estimate and confidence interval are not reported in the registry record, so the endpoint’s observed value and precision cannot be described. The registry also says that the primary endpoint population combined patients from this study with patients from a follow-up study; 27 patients from this study met eligibility requirements for that meta-analysis. That population detail should be kept in mind when interpreting the endpoint, rather than assuming the reported estimand would apply only to all 32 enrolled participants in this trial.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry identifies the primary endpoint as a 5-year relapse-free survival rate and states that it was estimated using the product-limit method of Kaplan and Meier. It defines the time origin as initial peripheral blood progenitor cell rescue and the event as death or disease recurrence; progression is the event for patients with stage IV disease. The record does not report the numerical estimate, its 95% confidence interval, the event count, or the number of participants contributing to the endpoint analysis.

What does Kaplan-Meier estimation mean?

As a general statistical explanation, Kaplan-Meier estimation is a way to describe time until an event when participants can have differing follow-up durations. A participant who has not had an event by their last known follow-up is censored at that time: their observed follow-up contributes information up to that point, but their later event status is unknown. The method uses the observed event times and the participants still under observation at those times to estimate the event-free experience over follow-up. It relies on assumptions about how censoring relates to the event process. The registry does not report the censoring pattern or describe how that assumption was assessed.

A confidence interval communicates uncertainty around an estimated quantity. In general, it gives a range of values compatible with the data under the statistical model and its assumptions. A narrower interval indicates greater precision than a wider interval, but does not by itself establish that the analysis is unbiased or that a treatment caused the observed result. Although the registry metadata names a 95% confidence interval, the numerical interval is not reported in the registry record. Precision therefore cannot be assessed for this endpoint.

How should the time point and event definition be read?

The endpoint’s 5-year label identifies the time horizon of interest. The event definition is consequential: death and recurrence count for the stated endpoint, while disease progression is specified for stage IV disease. The description defines relapse as appearance of any new lesions during or after protocol treatment and says histological documentation should be used whenever possible. Different event definitions can produce different estimates, so this definition is part of what the endpoint means. The record does not say how many recurrences were histologically documented or how ambiguous events were adjudicated.

The primary endpoint description states that patients in this study were combined with patients from a follow-up study, with 27 patients from this trial meeting eligibility requirements for meta-analysis. This means the described population is not simply identified as all 32 enrolled participants. The exact combined analysis population, eligibility rules for inclusion, and handling of participants not included are not reported in the registry record. The numerical endpoint result is also absent, so the population’s relationship to the estimate cannot be evaluated further.

What does non-randomized allocation imply?

The record labels allocation as non-randomized and masking as none. In general, random allocation helps reduce systematic differences between treatment groups at the start of a study. Non-random allocation can leave groups differing in prognosis, disease features, or other factors related to treatment selection. As a result, a comparison between arms may reflect both treatment and group composition. The registry explicitly notes that the arms are not a like-for-like control comparison. No adjusted comparative estimate or statistical analysis details are reported in the registry record.

Masking concerns whether participants, clinical staff, or assessors know the assigned treatment. The registry records no masking, but does not specify further how outcome assessment was conducted. General concerns can include influence on clinical management or assessment, depending on the endpoint and the procedures used; the record does not document whether such influences occurred in this study.

What is not documented about the analysis?

The registry record does not report the statistical analysis plan, a sample-size justification, a prespecified interim-analysis plan, or a detailed account of analysis populations. It reports no posted analyses. It does not provide a numerical primary outcome result or a statistical comparison between arms. These omissions mean that readers cannot assess whether the analysis followed a prespecified plan, how missing observations were handled, or whether any analysis adjustments were used. General statistical principles cannot fill those study-specific gaps.

For time-to-event data, general analysis considerations include censoring, event definitions, follow-up completeness, and the relationship between treatment groups and baseline prognosis. For a non-randomized study, adjustment for measured factors may sometimes be used, but it cannot necessarily account for unmeasured differences. Whether adjustment was conducted, which covariates might have been considered, and how model assumptions were assessed are not reported in the registry record. No new analysis can be inferred from the endpoint description alone.

10. Multiplicity, Missing Data and Analysis Populations

The registry record does not report a statistical analysis plan or an account of how multiple outcomes or comparisons were handled. It lists two outcome measures and no posted analyses, but does not state whether the primary endpoint was the only confirmatory analysis, whether subgroup analyses were planned, or how any multiplicity would have been controlled. When several hypotheses are tested, the chance of at least one apparently unusual result can increase; this is a general statistical concern. It cannot be determined from this record whether or how that issue affected the study.

Missing data and incomplete follow-up are especially relevant to time-to-event outcomes. Kaplan-Meier methods can incorporate censored follow-up, but interpretation depends on the nature of censoring and the amount of follow-up available. The registry does not report the number or timing of censoring events, reasons for loss to follow-up, missing endpoint assessments, or sensitivity analyses. It also does not report the handling of missing safety data.

The endpoint population is described as combining patients from this study with patients from a follow-up study; 27 patients from this study met eligibility requirements for meta-analysis. The record does not explain the eligibility criteria, identify the full analysis population, or account for participants who did not meet those requirements. It does not report whether analyses were based on all enrolled participants, treated participants, or another defined group. These are not interchangeable populations, and the missing details limit interpretation of the primary estimate.

The record also does not report interim analyses, stopping rules, or a sample-size justification. Their absence from the registry record should not be taken as evidence that they did or did not occur; these details are simply 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 0% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: disseminated intravascular coagulation (3.1%), febrile neutropenia (3.1%), adrenal insufficiency (3.1%), endocrine disorder (3.1%), chills (3.1%).

The registry lists 32 participants at risk for serious adverse events, with 24 affected. For other adverse events, it lists 32 at risk and 30 affected. These figures describe the recorded numbers of participants at risk and affected; they do not, by themselves, provide event timing, severity distribution beyond the serious-event classification, or a comparison between treatment groups. Death counts are not reported in the registry record.

The listed serious adverse event terms are disseminated intravascular coagulation, febrile neutropenia, adrenal insufficiency, endocrine disorder, chills, and fatigue. Each is reported at 3.1%. The registry does not provide additional details in this record about event onset, duration, recurrence, relationship to treatment, or outcomes. The percentages should therefore be read as the posted summaries for the named terms, not as a complete safety profile or as evidence of a causal relationship.

Safety interpretation depends on consistent definitions, observation periods, and information about how many participants were assessed. A general limitation of event summaries is that counts do not capture all aspects of clinical importance, and totals for participants with events are not equivalent to counts of individual event episodes. The record does not explain whether participants could contribute to more than one term or provide arm-specific safety results. The non-randomized design also limits direct comparisons across arms.

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

The registry record documents a phase II study of intensive chemotherapy, with or without trastuzumab, followed by autologous stem cell transplantation and radiation therapy for patients with stage III or stage IV breast cancer. It identifies a 5-year relapse-free survival endpoint and describes how that endpoint was intended to be measured. It also records selected adverse-event counts and terms. These registry entries describe the study’s scope and posted information; they do not establish the size, precision, or direction of an outcome effect.

The primary endpoint’s numerical estimate and 95% confidence interval are not reported in the registry record. The number of events and detailed analysis population are also not reported. As a result, the record does not allow a quantitative statement about relapse-free survival at the stated time point. A missing result should not be interpreted as a result of zero, as evidence of benefit, or as evidence of no effect.

The study was non-randomized, and the registry cautions that its arms are not a like-for-like control comparison. Consequently, the record does not support a causal conclusion about whether one arm or treatment component changed outcomes relative to another. In particular, no comparative effect of trastuzumab can be inferred from the treatment descriptions alone. Differences in patient characteristics or treatment selection could contribute to any apparent differences, and arm-level outcome estimates are not reported in the registry record.

The safety entries offer a limited descriptive account: 24 of 32 participants at risk are listed as affected by serious adverse events, and 30 of 32 are listed as affected by other adverse events. Named serious event terms are reported at 3.1% each. Without further context, these summaries do not quantify comparative risk, establish causality, or provide a complete account of harms.

The term “completed” indicates the study status recorded in the registry. It does not establish that the primary objective was met or that the results were conclusive. The record supports a description of the design, endpoint definition, and selected safety data, while leaving the central numerical outcome and important analysis details unresolved.

13. Why This Trial Matters Statistically

This study is statistically notable for the combination of a time-to-event primary endpoint and a non-randomized, multi-arm treatment design. The endpoint uses relapse-free survival over a stated horizon, with death or recurrence as events and progression specified for stage IV disease. Its definition illustrates why an endpoint’s event rules, time origin, and target population need to be examined alongside its label. The registry specifies Kaplan-Meier estimation but does not post the resulting estimate or its confidence interval.

The design also illustrates an important distinction between parallel treatment groups and randomized comparison groups. Parallel arms describe the study structure, but non-randomized allocation does not ensure that groups have comparable prognosis. The registry itself cautions that the arms are not a like-for-like control comparison. This prevents a simple arm contrast from being treated as an unbiased estimate of comparative treatment effect.

Another statistical issue is the endpoint population. The registry says the primary analysis combined patients from this study with patients from a follow-up study, and that 27 patients from this study met eligibility requirements for meta-analysis. This makes transparency about the analysis set especially important. The record does not provide the full combined population, eligibility rules, or numerical estimate, leaving readers unable to assess the endpoint’s precision or representativeness.

Finally, the record demonstrates why a study’s completion status and safety counts should not be confused with a complete outcome report. The registry gives selected adverse-event summaries, but not enough detail for comparative safety conclusions. With no primary numerical result, analysis plan, or account of missing follow-up, the appropriate statistical reading is bounded: the record describes what was studied and how the primary outcome was defined, while not permitting a quantitative efficacy conclusion.

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 most important limitation of the registry record is that it does not report the numerical primary endpoint result or its 95% confidence interval. It also omits the event count and the number of participants included in the endpoint estimate. The reader therefore cannot assess the observed relapse-free survival rate or its precision from this record.

The endpoint population is described as a combination of patients from this study and a follow-up study, with 27 patients from this trial meeting eligibility requirements for meta-analysis. The full combined analysis population, inclusion criteria, and relationship between the analysis set and the 32 enrolled participants are not reported in the registry record. This complicates interpretation of the target population represented by the primary outcome.

Non-randomized allocation and no masking limit comparative interpretation. The registry specifically says the arms are not a like-for-like control comparison. The arm descriptions are incomplete, and the record does not provide a full account of allocation, baseline characteristics, treatment received, or arm-specific outcomes. It is therefore not possible to determine from this record whether groups differed at baseline or how those differences might affect any comparison.

Further limitations include the absence of a statistical analysis plan, sample-size justification, interim-analysis information, detailed missing-data procedures, and a description of analysis populations. The record does not report censoring patterns, reasons for loss to follow-up, or sensitivity analyses for the time-to-event endpoint. Safety information is also limited to selected counts and named terms, without arm-specific figures or details on timing and attribution. These are limitations of the information recorded, and should not be taken to establish what was or was not done outside the registry record.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Combination Chemotherapy With or Without Trastuzumab Followed By an Autologous Stem Cell Transplant and Radiation Therapy in Treating Patients With Stage III or Stage IV Breast Cancer — NCT00182793.
• Registry record last updated 2017-02-23; status last verified 2017-01.
• Results first posted 2017-02-23.
• 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 completed phase II study enrolled 32 participants with stage III or stage IV breast cancer. It used non-randomized allocation, no masking, and parallel arms. The treatment strategy involved intensive chemotherapy, with or without trastuzumab, followed by autologous stem cell transplantation and radiation therapy. City of Hope Medical Center is listed as sponsor. The recorded start was 2005-07, and primary completion was 2014-10.

The primary endpoint was the 5-year relapse-free survival rate, estimated using the Kaplan-Meier product-limit method. Its population description states that patients from this study were combined with patients from a follow-up study; 27 patients from this study met eligibility requirements for meta-analysis. The numerical endpoint estimate, confidence interval, and event count are not reported in the registry record.

Safety summaries list 24 of 32 participants at risk as affected by serious adverse events and 30 of 32 as affected by other adverse events. Six named serious adverse event terms are each reported at 3.1%. The registry cautions that the non-randomized arms are not a like-for-like control comparison. The record does not support a quantitative conclusion about primary efficacy or comparative treatment effects.