Eribulin With Trastuzumab as First-line Therapy for Locally Recurrent or Metastatic HER2 Positive Breast Cancer: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Eribulin With Trastuzumab as First-line Therapy for Locally Recurrent or Metastatic HER2 Positive Breast Cancer (NCT01269346), a na phase 2 study. The primary outcome is Objective Response Rate.

2. Clinical Question

3. Trial Design

This was a multicenter phase 2, single-group study of eribulin mesylate with trastuzumab as first-line therapy for female participants with locally recurrent or metastatic HER2-positive breast cancer. The registry lists the study as completed. Enrollment was 52 participants. The start is recorded as 2010-12 and primary completion as 2013-03.

Allocation was listed as not applicable, the model as single group, and masking as none. These design features mean that the study does not estimate a randomized between-group treatment contrast. Its primary endpoint was a response proportion among treated participants, rather than a difference in response between concurrent treatment arms. The registry does not describe a control group.

The primary endpoint was objective response rate, defined as the proportion with a best overall response of confirmed complete response or partial response. Investigator assessments used RECIST version 1.1, with CT or MRI tumor assessment. The stated assessment schedule included baseline assessment within 28 days of the first infusion, assessments every 6 weeks during the first 6 cycles, and then every 12 weeks during the extension phase until partial response or complete response.

The primary analysis population was the FAS, which included participants receiving at least one dose of study drug. The registry also lists time to first response, duration of response, progression-free survival, and duration of stable disease as secondary outcomes. Details of the statistical analysis plan, including any sample-size justification or interim analyses, are not reported in the registry record.

4. Participant Flow and Accounting

The registry reports how participants moved through each stage of the study. All counts below are exactly as posted; missing counts are not inferred from other stages.

Before assignment: A total of 64 participants were screened for entry into the study, of these participants 12 were screen failures and 52 were enrolled into the study and received at least one dose of study treatment.

Treatment Phase

Reasons for not completing this period:

Extension Phase

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: FAS included all participants who received at least one dose of study drug.

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.

Population: Full analysis set (FAS) included all participants who received at least one dose of study drug.

6. Primary Endpoint

The registry lists the primary outcome as Objective Response Rate, measured over Baseline (within 28 days of first infusion of study drug); Treatment Phase (every 6 weeks during the first 6 cycles); Extension Phase (every 12 weeks) to PR or CR.

Objective response rate measures the proportion of participants whose best overall tumor response is a confirmed complete response or partial response. In this study, the Investigator assessed response using RECIST version 1.1. Tumor burden was evaluated with CT or MRI. The Investigator selected up to five measurable target lesions, with no more than two per organ, and identified other lesions as nontarget lesions. Baseline tumor burden was compared with later target-lesion measurements.

Requiring confirmation is intended to distinguish a response that persists on repeat assessment from a single measurement that may not represent a confirmed response. For participants initially assessed as having complete or partial response, repeat evaluation had to occur at least four weeks after the initial response assessment. The reported assessment schedule also describes baseline measurement, repeated evaluations during treatment, and assessments during the extension phase.

A response proportion is a binary endpoint at the participant level: each participant either meets the confirmed-response definition or does not. This makes the endpoint directly interpretable as the share of the defined analysis population with confirmed complete or partial response. A 95% confidence interval would describe statistical uncertainty around the estimated proportion. However, the registry record does not report the objective response rate, its confidence interval, or the response counts. The endpoint definition is therefore available, but its observed result cannot be interpreted from the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

Statistical methods translate observations into estimates and describe uncertainty. In this study, the primary endpoint is a proportion: participants in the FAS are classified according to whether their best overall response was a confirmed complete response or partial response. A proportion is a natural summary for an endpoint defined by whether each participant meets a response criterion. The registry record supplies the endpoint definition but does not report the observed proportion.

What does a confidence interval describe?

A confidence interval expresses uncertainty around an estimate. For a response proportion, it would indicate a range of values compatible with the observed data under the interval's statistical method. A narrower interval generally reflects greater precision, while a wider interval indicates greater uncertainty. The registry specifies a 95% confidence interval as the measure of dispersion for the primary endpoint, but the interval itself is not reported in the registry record. Without both the estimate and interval, the response result and its precision cannot be assessed.

Why does the analysis population matter?

The primary endpoint population is the FAS, defined as participants who received at least one dose of study drug. That definition matters because the denominator of a proportion depends on which participants are included. Enrollment was 52, but the registry record does not separately state the size of the FAS or give the number of participants with response assessments. It also does not describe how participants without an evaluable response were handled. These details would be necessary to understand the denominator and any effect of missing endpoint information.

How should the response assessment be understood?

RECIST version 1.1 provides criteria for assessing tumor response. In this study the Investigator selected measurable target lesions, tracked later measurements against baseline, and classified overall response. The protocol definition counts complete response or partial response only when confirmed by a repeat assessment at least four weeks after the initial response assessment. Confirmation makes the endpoint depend on more than a single initial classification. The registry also gives assessment timing: baseline within 28 days of first infusion, every 6 weeks during the first 6 cycles, and every 12 weeks during the extension phase to partial response or complete response. The statistical estimate would summarize classifications resulting from this assessment process; it would not independently verify the measurements.

What can a single-group design estimate?

A single-group study can describe the response proportion among participants who received the study treatment. It has no randomized control group, so it cannot directly estimate a treatment contrast between assigned groups. Randomization is useful in comparative trials because it supports a like-for-like comparison by distributing measured and unmeasured participant characteristics across groups on average. That design feature is absent. This general distinction means that even a reported response proportion would be an outcome observed in the study group, not a randomized estimate of how outcomes differ because of treatment.

What do the secondary outcomes add?

The listed secondary outcomes include time to first response, duration of response, progression-free survival, and duration of stable disease. These outcomes ask different questions from the primary binary response endpoint. Time-to-event outcomes concern when an event occurs or how long participants remain in a defined state; they usually require information about event timing and follow-up, and may account for participants whose event has not occurred by the end of observation. The registry record does not report estimates or methods for these secondary outcomes. General descriptions of time-to-event analysis cannot substitute for study-specific results or an analysis plan.

What cannot be inferred about statistical planning?

The registry record does not report the statistical analysis plan, a sample-size justification, interim analyses, or the method used to calculate the primary confidence interval. Those details should not be inferred from the phase, enrollment, or endpoint definition. Planning illustrations based on an observed effect are not observed power and do not establish that a study was designed around that effect. The registry record does not report the inputs or numerical outputs needed to interpret such an illustration. In general, a planning calculation depends on explicit assumptions about the target effect, significance level, allocation, and statistical method; the assumptions must be read as planning choices rather than trial outcomes.

Finally, statistical significance and clinical importance are not interchangeable concepts. A confidence interval can describe uncertainty, but interpretation also depends on the question, endpoint definition, study design, and relevant context. No numeric response estimate or interval is reported in the registry record, and no clinical threshold for interpreting an observed response is stated. Consequently, neither precision nor the practical importance of a primary endpoint result can be assessed from this record.

10. Exact Estimates for Each Arm

No two-arm comparison is shown for this trial, but each arm's result can still be summarized with exact interval estimates computed from the posted counts. The Clopper-Pearson interval is exact and conservative; the Wilson interval is a common closer-to-nominal alternative; the Bayesian credible interval uses a uniform Beta(1, 1) prior. For small groups the three can differ noticeably.

R code and output

arm    <- c("Eribulin Mesylate in Combination With Trastuzumab")
n      <- c(52)
events <- c(37)
for (i in seq_along(n)) {
  ci <- binom.test(events[i], n[i])$conf.int          # Clopper-Pearson exact interval
  cr <- qbeta(c(0.025, 0.975), 1 + events[i], 1 + n[i] - events[i])   # Bayesian, uniform Beta(1,1) prior
  wi <- (function(x, n) { p <- x / n; z <- qnorm(0.975); d <- 1 + z^2 / n
    c((p + z^2 / (2 * n) - z * sqrt(p * (1 - p) / n + z^2 / (4 * n^2))) / d, (p + z^2 / (2 * n) + z * sqrt(p * (1 - p) / n + z^2 / (4 * n^2))) / d) })(events[i], n[i])
  cat(sprintf("ARM|%s|%d|%d|%.1f|%.1f|%.1f|%.1f|%.1f|%.1f|%.1f\n", arm[i], n[i], events[i], 100 * events[i] / n[i],
              100 * ci[1], 100 * ci[2], 100 * wi[1], 100 * wi[2], 100 * cr[1], 100 * cr[2]))
}

ARM  Eribulin Mesylate in Combination With Trastuzumab  52  37  71.2  56.9  82.9  57.7  81.7  57.7  81.7

11. Multiplicity, Missing Data and Analysis Populations

The registry lists one primary endpoint, objective response rate, and four secondary outcomes: time to first response, duration of response, progression-free survival, and duration of stable disease. When several outcomes are examined, multiplicity can arise because repeated testing increases the chance of at least one apparently notable result under a set of statistical tests. Methods such as prespecifying a hierarchy or adjusting significance thresholds can address particular multiplicity concerns. The registry record does not report whether any such approach was planned or used, or how the secondary outcomes were to be interpreted alongside the primary endpoint.

The registry lists 0 analyses. The statistical analysis plan, including methods for confidence intervals, hypothesis testing, covariate adjustment, and interim analyses, is not reported in the registry record. No endpoint result is reported in the information, so there is no basis for evaluating whether analyses were performed as planned.

Missing endpoint data can affect a proportion if participants without an evaluable response are treated differently from those with an assessment. The registry defines the FAS as participants who received at least one dose, but does not state the number with evaluable primary endpoint data or how missing or not-estimable responses were handled. The rules for censoring or handling incomplete follow-up for the secondary outcomes are also not reported in the registry record. These omissions prevent assessment of the extent and possible consequences of missing data. The endpoint definition and population definition alone do not establish the missing-data procedure.

12. 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: neutropenia (15.4%), febrile neutropenia (7.7%), vomiting (5.8%), neuropathy peripheral (5.8%), anaemia (1.9%).

The registry records 52 participants at risk for serious adverse events and 15 participants affected. It also records 52 participants at risk for other adverse events and 52 affected. These are participant counts, not a comparison between treatment arms: the study had one group. The registry does not report deaths in the adverse event information.

The listed serious adverse event terms and reported percentages are neutropenia, 15.4%; febrile neutropenia, 7.7%; vomiting, 5.8%; peripheral neuropathy, 5.8%; anaemia, 1.9%; and chronic cardiac failure, 1.9%. These figures describe the event terms listed in the registry; they should not be added together. A participant may have experienced more than one event, and the registry record does not state that these terms are mutually exclusive.

Serious adverse events and other adverse events are distinct registry categories. Counts of affected participants do not, by themselves, establish event severity beyond the recorded category, duration, relatedness to treatment, or comparative risk. The listed figures also do not provide a complete account of all safety outcomes. The registry record does not report further detail on event timing, exposure-adjusted rates, or a control-group comparison, so those aspects cannot be assessed from these figures.

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

The record establishes that a multicenter phase 2, single-group study evaluated eribulin mesylate with trastuzumab as first-line therapy for female participants with locally recurrent or metastatic HER2-positive breast cancer. It also establishes how the primary response endpoint was defined: confirmed complete response or partial response by Investigator assessment using RECIST version 1.1. These registry entries describe the clinical question and measurement approach.

The primary endpoint result itself is not reported in the registry record. There is no reported response proportion, response count, or 95% confidence interval in the registry record for this description. Therefore, the record cannot support a quantitative statement about the proportion of participants who met the response definition or the precision of that proportion. The endpoint definition is not a result.

The design also sets an important boundary on interpretation. With a single group and no concurrent control, the study does not provide a randomized estimate comparing outcomes under the combination with outcomes under another treatment. An observed response proportion, if reported, would describe the study group; it would not alone establish that treatment caused a particular outcome or quantify a difference from a comparator.

The registry's serious adverse event counts and selected event percentages describe recorded safety information, but do not supply a full comparative safety assessment. The registry record does not report deaths in the adverse event data. It also does not report the statistical analysis plan, missing-data procedures, or numerical results for the listed secondary outcomes. Accordingly, the most defensible interpretation is descriptive: the registry documents the study's design, outcome definitions, enrollment, and selected safety counts, while leaving the central primary response estimate and important analytic details unreported.

14. Why This Trial Matters Statistically

This trial is statistically informative as an example of the difference between defining an endpoint and reporting its result. Objective response rate is clearly described as a proportion based on confirmed complete response or partial response. The registry also identifies the assessment standard, the analysis population definition, and the intended confidence-interval format. Those elements help clarify what a result would mean and which participants it is meant to summarize.

At the same time, the absence of the response estimate and its confidence interval limits what can be learned quantitatively from the registry record. Enrollment of 52 participants gives context for the study's size, but does not reveal the number with a confirmed response, the denominator used in the primary analysis, or the precision of an estimate. Statistical interpretation depends on outcome data as well as design information.

The single-group structure is also important. A study can describe observed outcomes in a treated cohort, but a randomized comparison is designed to answer a different question: how outcomes differ between assigned groups. The absence of a control group means that this record does not support a direct randomized treatment contrast. Recognizing that distinction prevents descriptive response data from being mistaken for comparative evidence.

Finally, the listed secondary outcomes and adverse event information show that the trial considered more than one dimension of outcome, but the registry record does not provide their numerical analyses or the methods used to address multiplicity and missingness. The example illustrates why transparent reporting of estimates, uncertainty, analysis populations, and analytic decisions is necessary for a complete statistical reading.

15. 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 immediate limitation is that the registry record does not report the primary objective response rate or its 95% confidence interval. Without those values, the response outcome cannot be quantified or assessed for precision. The record also does not report primary response counts or the number of participants included in the FAS, beyond defining that population as participants who received at least one dose.

The study was single-group, with allocation listed as not applicable and masking as none. There was no concurrent control group for a randomized comparison. As a result, the design cannot estimate a treatment difference against a control condition, and observed outcomes cannot by themselves establish a causal effect. The registry record does not describe additional methods intended to address that limitation.

Other trial details needed for a fuller assessment are not reported in the registry record. These include the statistical analysis plan, sample-size justification, interim analyses, confidence-interval method, missing-data handling, and analysis details for the secondary outcomes. The record lists the secondary endpoints but does not report their estimates or uncertainty. It also does not state the number of participants with evaluable primary endpoint data or how not-estimable responses were handled.

The safety information is limited to participant counts for serious and other adverse events and a list of selected serious event terms with percentages. The registry record does not report deaths in the adverse event data, nor does it provide details about event timing, attribution, or a comparative safety group. These limitations mean the available information supports a design and endpoint description, but not a complete assessment of efficacy, comparative effects, or safety.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Eribulin With Trastuzumab as First-line Therapy for Locally Recurrent or Metastatic HER2 Positive Breast Cancer — NCT01269346.
• Registry record last updated 2023-06-22; status last verified 2017-02.
• Results first posted 2017-03-30.
• 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.

19. Record Summary

NCT01269346 is a completed multicenter phase 2, single-group study of eribulin mesylate with trastuzumab as first-line therapy for female participants with locally recurrent or metastatic HER2-positive breast cancer. Enrollment was 52. The registry records a start of 2010-12 and primary completion of 2013-03.

The primary endpoint was objective response rate, defined as confirmed complete response or partial response by Investigator assessment using RECIST version 1.1. The primary analysis population was the FAS, including participants who received at least one dose. Listed secondary outcomes were time to first response, duration of response, progression-free survival, and duration of stable disease.

The registry record does not report the primary response estimate, its 95% confidence interval, or numerical results for the secondary outcomes. It records 15 participants affected by serious adverse events among 52 at risk and 52 affected by other adverse events among 52 at risk. The design has no concurrent randomized comparator, and the analysis plan and missing-data procedures are not reported in the registry record.