A Study of Single-Agent Eribulin Mesylate as First-Line Therapy for Locally Recurrent or Metastatic Human Epidermal Growth Factor Receptor Two (HER2) Negative Breast Cancer: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for A Study of Single-Agent Eribulin Mesylate as First-Line Therapy for Locally Recurrent or Metastatic Human Epidermal Growth Factor Receptor Two (HER2) Negative Breast Cancer (NCT01268150), a na phase 2 study. The primary outcome is Objective Response Rate (ORR).

2. Clinical Question

3. Trial Design

This was a Phase 2, multicenter, single-arm study of single-agent eribulin mesylate as first-line therapy for locally recurrent or metastatic HER2-negative breast cancer. The registry record lists an enrollment of 56 and one experimental group. Allocation is listed as not applicable, masking as none, and the study model as single group. Thus, the design does not include a randomized or blinded comparison between treatment groups.

The study start is recorded as 2011-02, and primary completion as 2012-03. The study status is completed. The primary endpoint assessment period began at Cycle 1 (Day 1) and continued until first evidence of disease progression, with assessment described as extending up to the data cutoff date of 30 Aug 2013 and up to 2.5 years. These dates and the stated assessment window describe the registry record; they do not establish how often each participant was assessed.

The primary endpoint was objective response rate, defined using confirmed complete or partial responses. Secondary outcomes listed in the registry record were time to first response, duration of response, and progression-free survival. The record does not report the primary endpoint result. It also does not report the details of a statistical analysis plan, a sample-size justification, interim analyses, or a comparator-based hypothesis test. Such details should not be inferred from the phase label or from the fact that enrollment was 56.

Because the study has one treatment group, its design can describe outcomes observed among participants treated in the study, if those results are reported. It cannot, by itself, separate a treatment effect from other explanations for an outcome or estimate a randomized treatment contrast.

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.

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: Full analysis set included all participants who received at least one dose of eribulin mesylate.

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 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 (ORR), measured over Cycle 1 (Day 1) until first evidence of disease progression, assessed up to the data cutoff date (30 Aug 2013) up to 2.5 years.

The primary endpoint was objective response rate (ORR), expressed as the percentage of participants whose best overall response was a confirmed complete response (CR) or partial response (PR). The registry record specifies RECIST version 1.1 and investigator assessment of target lesions evaluated by computed tomography or magnetic resonance imaging. A CR required disappearance of all target lesions. A PR required at least 30% decrease in the sum of target-lesion diameters relative to the baseline sum. A possible CR or PR required confirmation no fewer than 4 weeks after the initial response assessment. The record also describes brain and bone scans after response confirmation to check for new metastases.

As a general statistical concept, response rate reduces a pattern of tumor measurements to a binary outcome: each participant either meets the specified response definition or does not. The resulting percentage is a readily interpretable summary of the proportion meeting the criterion. It does not, by itself, describe how long a response lasts, when response begins, or how outcomes compare with an alternative treatment. The registry record lists duration of response, time to first response, and progression-free survival as secondary outcomes, but their results are not reported in the registry record.

The ORR value and its uncertainty are not reported in the registry record. Consequently, the response definition can be described, but the frequency and precision of observed response cannot be assessed from the posted results.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

What kind of outcome is ORR?

ORR is a binary-outcome summary. Under the registry definition, each participant’s best overall response is classified according to whether a confirmed complete response or partial response was achieved. The percentage is the proportion of the analysis population classified as meeting that response definition. This kind of outcome is different from a continuous measure, such as a change in a laboratory value, and different from a time-to-event outcome, such as time until progression.

The classification depends on the stated response rules, not merely on whether a measurement changes. The record specifies RECIST version 1.1, investigator assessment, imaging of targeted lesions, confirmation of possible responses no fewer than 4 weeks after the initial assessment, and additional scans after confirmation to check for new metastases. Those rules define what counts as a response. The record does not report the number classified as CR or PR, the number not meeting either definition, or the resulting ORR.

What does an estimate’s precision mean?

As a general statistical explanation, a point estimate is a single summary calculated from observed data, while a confidence interval communicates uncertainty around that estimate under a specified statistical method. For a percentage, uncertainty depends on the observed data and the method used to construct the interval. A narrower interval indicates greater statistical precision under that method; it does not eliminate possible bias or make a result causal.

No ORR estimate or confidence interval is reported in the registry record. It is therefore not possible to describe the size or precision of the primary result. The registry record also does not report a statistical analysis plan that would identify the method used for an interval, any adjustment, or a prespecified decision threshold.

Why does the single-arm design matter?

As a general statistical explanation, a single-arm study estimates outcomes within the participants who received the study treatment. A randomized comparison instead assigns participants to groups and estimates a contrast between those groups. Randomization can help balance measured and unmeasured factors on average; without a concurrent randomized comparator, observed outcomes in one group cannot alone establish what would have happened under another treatment.

This study is recorded as single-group, with allocation listed as not applicable and masking listed as none. The record therefore does not describe a treatment-versus-control comparison. A response percentage, if reported, would answer how often the defined response was observed in the analysis population, not what the response rate would have been under a different treatment.

How should the analysis population be understood?

The registry record says the full analysis set included all participants who received at least one dose of eribulin mesylate. This definition identifies who was intended to contribute to the primary endpoint analysis. It is not the same as saying that every enrolled participant necessarily had a reported evaluable response; the record does not give the analysis denominator or disposition details for the primary endpoint beyond the population definition and overall enrollment.

As a general concept, an analysis population definition matters because results can change depending on which participants are included and how participants without an evaluable outcome are handled. The registry record does not report missing-data methods, the number of missing primary assessments, or whether any participants were excluded from the endpoint analysis. Those details should not be inferred.

What can be said about statistical planning?

The registry record does not report the study’s sample-size justification, target effect, planned precision, or a formal hypothesis-testing plan. Enrollment of 56 is a reported study fact, not evidence by itself that the study was adequately powered for a particular question. As a general statistical concept, power is a design property calculated under assumptions about an effect, variability or event frequency, significance level, and analysis method. It is not a measure of the probability that a finding is true after results are observed.

Planning illustrations based on an observed effect are not observed power and should not be read as the trial’s original design justification. In particular, a two-arm planning calculation does not convert this single-arm study into a randomized comparison. The assumptions described for such illustrations include equal allocation between two arms, a two-sided significance level of 0.05, and a normal approximation; the registry record does not state that these were the trial’s own design assumptions.

What is not available for evaluating the analyses?

The registry record lists five outcome measures and three named secondary outcomes, but it reports zero analysis entries. The record does not give the primary ORR result, confidence interval, p-value, or analysis-specific participant count. It also does not report an interim-analysis plan, multiplicity adjustment, or details of statistical models. These absences limit assessment of how outcomes were analyzed and how uncertainty was quantified.

As a general statistical concept, over-dispersion matters when observed variability exceeds what a chosen model assumes; a model that ignores it can understate uncertainty. The registry record does not identify a model for the binary endpoint or provide data that would permit assessment of over-dispersion. No model-specific conclusion is warranted.

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")
n      <- c(56)
events <- c(16)
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  56  16  28.6  17.3  42.2  18.4  41.5  18.4  41.5

11. Multiplicity, Missing Data and Analysis Populations

The registry record lists objective response rate as the primary outcome and names time to first response, duration of response, and progression-free survival as secondary outcomes. It does not report a multiplicity strategy, such as a prespecified ordering of tests or an adjustment for examining several outcomes. Without that information, the handling of multiple statistical comparisons is not reported in the registry record. No analysis entries are listed, and results for the secondary outcomes are not reported in the registry record.

The full analysis set is defined as all participants who received at least one dose of eribulin mesylate. This identifies the intended primary analysis population, but the record does not report how many participants contributed an evaluable primary outcome or whether any participants were excluded from that analysis.

Missing-data methods, the number of participants with missing response assessments, and the reasons for missing assessments are not reported in the registry record. As a general statistical concept, missing outcomes can affect a percentage estimate if participants with missing status differ from those with observed status. The direction and size of any such effect cannot be determined without information on missingness and the analysis method.

The record also does not report interim analyses or a statistical plan for handling repeated assessment. The primary outcome timeframe describes when assessment could occur, but it does not specify the analysis rules for participants whose follow-up ended before the data cutoff.

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: febrile neutropenia (5.4%), neutropenia (5.4%), pulmonary embolism (3.6%), leukopenia (1.8%), pericardial effusion (1.8%).

The registry safety fields list 56 participants at risk for serious adverse events and 17 affected. For other adverse events, the record lists 56 at risk and 56 affected. These are separate registry categories; the figures do not show how many distinct participants experienced both categories or how many events each participant experienced.

The serious adverse-event terms with listed percentages are febrile neutropenia, 5.4%; neutropenia, 5.4%; pulmonary embolism, 3.6%; leukopenia, 1.8%; pericardial effusion, 1.8%; and supraventricular tachycardia, 1.8%. These term-specific percentages are not a complete description of all events, and the record does not establish that the listed categories are mutually exclusive. The deaths field has no reported value; it should not be read as evidence that there were no deaths.

As a general statistical point, adverse-event summaries describe events recorded during a study and do not, by themselves, establish that the treatment caused each event. The registry record does not provide a comparator group for evaluating relative safety. These figures therefore describe the posted safety information for the study group, not a comparative risk estimate.

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

The record establishes that a Phase 2, multicenter, single-arm study evaluated single-agent eribulin mesylate as first-line therapy for locally recurrent or metastatic HER2-negative breast cancer. It defines a primary endpoint based on confirmed complete or partial response using RECIST version 1.1. It also lists three secondary outcomes and provides selected adverse-event information.

What the record does not establish is the observed primary response rate. The ORR result and its precision are not reported in the registry record. Without those values, the frequency of confirmed response and the uncertainty around it cannot be evaluated. The secondary outcome results are likewise not reported in the registry record.

Even if an ORR estimate were available, the study’s single-arm design would not provide a randomized estimate of how outcomes compare with another treatment. As a general statistical point, an outcome observed in a treatment group is not the same as a treatment effect relative to a concurrent control. Differences in participant characteristics, disease course, assessments, and other factors can influence outcomes in a single group. The registry record does not support a causal comparison.

The safety figures describe the reported counts and selected serious-event terms. They do not, on their own, establish causation or comparative safety. The deaths field is unreported, not a reported count of zero. Likewise, the enrollment figure does not demonstrate that a particular statistical objective was met; the registry record does not report the sample-size justification or analysis plan.

The appropriate reading is therefore bounded: the registry record documents the study design, endpoint definitions, and some safety data, but does not report the primary efficacy result or enough analysis detail to assess its statistical precision. These omissions preclude interpreting an efficacy finding from the record and do not support conclusions about benefit relative to another therapy.

14. Why This Trial Matters Statistically

This trial is statistically informative as an example of the distinction between defining an endpoint and reporting its result. The registry record gives a detailed operational definition of objective response, including the confirmation requirement and imaging-based assessment. Those details make clear what the endpoint was intended to measure. They do not supply the observed response percentage, and a well-defined endpoint cannot substitute for a reported estimate.

The study also illustrates the limits of a single-arm design. Such a design can describe outcomes within the treated group, but it does not create a concurrent randomized counterfactual. The distinction matters when interpreting terms such as efficacy: a response outcome in one group is not by itself a comparative treatment effect. The registry record’s design fields make this limitation explicit.

Another statistical lesson is that enrollment and analysis populations are not interchangeable. The record reports enrollment of 56 and defines the full analysis set as participants who received at least one dose. It does not report endpoint-specific analysis counts or missing-data handling. Readers therefore cannot assume that enrollment is the denominator used for every endpoint.

Finally, the safety data illustrate why counts, event categories, and causal interpretation need to be kept separate. The record lists participants affected in serious and other adverse-event categories, selected serious-event terms, and no reported value for deaths. These fields describe the posted safety record but do not provide a randomized risk comparison. Taken together, the study highlights how design, endpoint definition, population, result reporting, and precision each shape what can be concluded.

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 main limitation for interpreting efficacy is that the registry record does not report the primary objective response rate. It also does not report a confidence interval or other measure of precision for that endpoint. The response criteria and assessment period are described, but the outcome value itself is unavailable in the registry record.

The study was single-arm, with no concurrent comparator. Even a reported response estimate would describe outcomes in the study group rather than a randomized difference between treatments. The registry record does not provide a basis for attributing observed outcomes to treatment relative to an alternative.

Although the primary population is defined as participants who received at least one dose, the endpoint-specific denominator and participant disposition are not reported. Missing-data methods, missing assessment counts, and handling of participants without an evaluable response are also not reported in the registry record. This makes it difficult to assess how the defined analysis population was represented in the endpoint calculation.

The registry record does not report the statistical analysis plan, sample-size justification, interim analyses, or multiplicity handling. It lists secondary outcomes but does not report their results. The deaths field is unreported, and selected serious adverse-event terms do not establish comparative safety or causation. These limitations apply to interpretation of the posted record and should not be filled in by assumptions about common practices in similar studies.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: A Study of Single-Agent Eribulin Mesylate as First-Line Therapy for Locally Recurrent or Metastatic Human Epidermal Growth Factor Receptor Two (HER2) Negative Breast Cancer — NCT01268150.
• Registry record last updated 2023-06-22; status last verified 2016-06.
• Results first posted 2016-08-09.
• 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

The registry record describes a completed Phase 2, multicenter, single-arm study of single-agent eribulin mesylate as first-line therapy for locally recurrent or metastatic HER2-negative breast cancer. Enrollment was 56. The primary endpoint was objective response rate, defined as the percentage with a confirmed complete or partial response under RECIST version 1.1 among participants who received at least one dose.

The record lists time to first response, duration of response, and progression-free survival as secondary outcomes. It also reports adverse-event counts and selected serious-event terms. The primary response result, secondary outcome results, statistical analysis plan, and missing-data methods are not reported in the registry record. Because there was no concurrent comparator, the design does not provide a randomized treatment comparison.