Study to Evaluate the Efficacy and Safety of Eribulin Mesylate Administered Biweekly (Q2W) for Participants With Human Epidermal Growth Factor Receptor 2 (HER2)-Negative Metastatic Breast Cancer: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Study to Evaluate the Efficacy and Safety of Eribulin Mesylate Administered Biweekly (Q2W) for Participants With Human Epidermal Growth Factor Receptor 2 (HER2)-Negative Metastatic Breast Cancer (NCT02481050), a na phase 2 study. The primary outcome is Objective Response Rate (ORR) by Investigator Assessment.

2. Clinical Question

3. Trial Design

This was a Phase 2, open-label, single-arm, multicenter study of eribulin mesylate for participants with HER2-negative metastatic breast cancer previously treated with 2 to 5 chemotherapy regimens. The study is described as 2-stage. The record does not report the operational details of those stages, such as their decision rules or how enrollment between stages was determined. The planned enrollment was 58, and the study status is completed.

Because every participant was assigned to the same study treatment and there was no control group, the design can describe outcomes observed during treatment but cannot directly estimate a treatment contrast against another regimen or against a concurrent untreated group. The allocation field is not applicable to a single-group design. Treatment was not masked, and the primary outcome was assessed by investigators. The record does not report whether any additional procedures were used to reduce assessment bias.

The primary outcome was objective response rate, defined using complete or partial response under RECIST 1.1. Secondary outcomes included investigator-assessed progression-free survival, overall survival, feasibility rate, and counts of participants with treatment-emergent adverse events and serious adverse events. The record lists 6 outcome measures, but the numerical primary endpoint result is not reported in the registry record. It also does not report numerical results for the listed secondary outcomes in the registry record for this analysis.

The study dates and status identify a completed trial, but completion alone does not establish that each planned outcome was reported. The registry record does not report the statistical analysis plan, the number included in the primary endpoint analysis, or the handling of participants who lacked an evaluable tumor assessment beyond the stated evaluable-set definition.

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 74 participants were screened, of which 16 were screen failures and 58 were randomized to receive study treatment.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: The evaluable analysis set (EAS) included all participants who had both an evaluable baseline tumor assessment and an evaluable postbaseline tumor assessment, unless the participants discontinued because of disease progression or toxicity.

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: The full analysis set (FAS) included all participants who received any amount of study drug.

6. Primary Endpoint

The registry lists the primary outcome as Objective Response Rate (ORR) by Investigator Assessment, measured over From first dose of study drug until intercurrent illness, unacceptable toxicity, disease progression, or until the participant withdrew consent (approximately up to 2.3 years).

The primary endpoint, objective response rate by investigator assessment, is the percentage of participants whose best overall response was complete response or partial response. Complete response was defined as disappearance of all target lesions, with a lymph node short diameter less than 10 mm where applicable. Partial response required at least a 30% decrease in the sum of target-lesion long diameters compared with baseline, according to RECIST 1.1.

Response rate is a binary-outcome summary: each participant is classified as having or not having a qualifying response under the endpoint definition, and the result is expressed as a percentage. It provides a direct description of the proportion of the specified analysis population meeting the response criteria. The 95% confidence interval is intended to convey uncertainty around that estimated percentage; it does not show the range of individual participant outcomes.

In this study, response was assessed by investigators rather than by a reported independent review. The endpoint timeframe extended from the first dose until an intercurrent illness, unacceptable toxicity, disease progression, or withdrawal of consent, described as approximately up to 2.3 years. The registry record does not report the observed percentage, its confidence interval, or the number of evaluable participants. As a result, neither the estimated response frequency nor its precision can be interpreted from the record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry record describes a percentage endpoint with a 95% confidence interval. A percentage for a binary outcome summarizes the fraction of an analysis population that met the stated response definition. A confidence interval communicates statistical uncertainty around the estimated percentage. In general, a narrower interval indicates greater precision, while a wider interval indicates less precision. It does not guarantee that the true value lies within the interval, and it does not describe the range of responses among individual participants.

What does the response classification represent?

For this endpoint, each participant’s best overall response is classified using RECIST 1.1. Complete response and partial response count toward the objective response endpoint; other response classifications do not meet the stated definition. The record specifies the lesion-change criteria used to define complete and partial response. Because the assessment was by investigators, the recorded response depends on investigator assessments under that framework. The record does not report an independent review process or other details about assessment quality control.

Why does the analysis population matter?

The primary analysis population was the evaluable analysis set. It included participants with evaluable baseline and postbaseline tumor assessments, except for participants who discontinued because of progression or toxicity. This definition sets the population to which the response percentage would apply. It is not necessarily the same as everyone enrolled or treated. The record does not report the size of the evaluable set or the number excluded from it. Without those details and the endpoint result, the reader cannot verify the analysis denominator or assess how the analysis population differed from the enrolled group.

In general, restricting a response analysis to participants with evaluable assessments can affect interpretation if missing assessments are related to prognosis or treatment experience. The direction of any such effect is not knowable from the definition alone. The record does not report how other missing or unevaluable assessments were handled, whether any imputation was used, or whether sensitivity analyses were performed.

What can a single-arm estimate establish?

A single-arm study estimates outcomes within the group receiving the study treatment. Such a result is descriptive of that group under the study conditions. It does not estimate a between-group difference because there is no concurrent comparator. Random allocation, which can balance known and unknown prognostic factors on average across groups, is not part of this design. Comparisons to historical outcomes would require additional information and assumptions; no such comparison is reported in the registry record.

The open-label design means that treatment masking was absent. For outcomes based on investigator assessment, knowledge of treatment can potentially influence measurement or interpretation. This is a general methodological consideration, not evidence that assessment bias occurred in this study. The registry record does not report procedures such as blinded review that could clarify this concern.

How should the planning illustrations be read?

Any sample-size illustrations associated with the posted results are planning calculations based on an observed effect, not observed power. The stated assumptions include a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. These are assumptions for an illustrative design calculation, not a description of the actual single-arm study’s allocation. The registry record does not provide the primary observed effect in the registry record, so the planning outputs cannot be interpreted as a numerical design recommendation for this study.

In general, a planning calculation asks how much information a future study might need to detect a chosen effect under specified assumptions. It does not measure the probability that the completed study has established an effect, nor does it alter the uncertainty in the observed result. Sample-size planning values are not observed power. Because this trial had a single group, a calculation based on equal allocation between two arms is a hypothetical planning framework rather than the trial’s design.

What is not available for statistical appraisal?

The registry record does not report the method used to calculate the confidence interval, any formal hypothesis test for the primary endpoint, or the statistical analysis plan. It does not report whether interim analyses were performed or what decision criteria governed the described 2-stage design. No recalculated result is available in the registry record recorded for this analysis. Without the endpoint estimate and denominator, a simple independent check of the response percentage or interval is not possible.

For a percentage, uncertainty is influenced by the amount of information in the analysis population and by the observed response pattern. General methods can use different approximations or exact procedures, with potentially different interval limits. The method matters particularly when data are sparse or the estimated percentage is near a boundary. No claim about which method is most suitable for this particular result can be made without the reported data and analysis details.

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 1.4 mg/m^2")
n      <- c(57)
events <- c(7)
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 1.4 mg/m^2  57  7  12.3  5.1  23.7  6.1  23.2  6.1  23.3

11. Multiplicity, Missing Data and Analysis Populations

The primary endpoint was objective response rate. The registry record also lists secondary outcomes, including investigator-assessed progression-free survival, overall survival, feasibility rate, and adverse-event outcomes. When a study evaluates several endpoints or makes repeated statistical tests, multiplicity can increase the chance of at least one apparently positive finding by chance. Statistical plans may address this by defining a testing hierarchy or adjusting significance levels. The registry record does not report a multiplicity procedure, a hierarchy among endpoints, or a complete statistical analysis plan. It is therefore not possible to determine whether or how multiplicity was addressed.

The record defines the evaluable analysis set for the primary endpoint, but does not report its size or the number of participants with missing or unevaluable tumor assessments. It specifies that participants who discontinued because of disease progression or toxicity were included in the set even without an evaluable postbaseline tumor assessment. It does not state how other missing assessments were classified or handled, whether missing outcomes were imputed, or whether sensitivity analyses were conducted.

Missing outcome information can matter if the likelihood of an assessment being unavailable is related to response or participant health. This is a general concern rather than a claim about what happened in this study. The registry record does not report enough detail to assess the amount, pattern, or potential influence of missing primary endpoint data.

The record does not report interim-analysis procedures or stopping rules for the 2-stage design. Those details are not inferable from the design label alone. Nor does it report whether the primary analysis followed a prespecified plan. These gaps limit assessment of the analysis process and the robustness of any efficacy interpretation.

12. 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

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: sepsis (3.4%), cancer pain (3.4%), constipation (1.7%), vomiting (1.7%), asthenia (1.7%).

The registry record reports serious adverse events for the eribulin mesylate group: 14 participants with serious adverse events among 58 at risk. It also reports other adverse events for 58 participants among 58 at risk, and 40 deaths. These are separate reported counts; they should not be combined or treated as mutually exclusive categories. The record does not provide the full timing, duration of follow-up, or participant-level overlap needed to interpret how the events relate to one another.

The listed serious adverse-event terms include sepsis and cancer pain at 3.4% each, and constipation, vomiting, asthenia, and chest pain at 1.7% each. These percentages describe terms reported in the registry record. They are not estimates of comparative risk, and no control group is available to support a treatment-to-treatment safety comparison. A listed event also does not by itself establish that study treatment caused it.

The registry record does not report detailed case narratives, severity distributions beyond the serious-event classification, or attribution for each event. The death count is not accompanied by a cause breakdown in the registry record for this analysis. Safety counts should therefore be read as descriptive records of events in the study group, not as evidence of causality or a comparative safety estimate.

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

The study was designed to describe the objective response rate during biweekly eribulin mesylate treatment in participants with HER2-negative metastatic breast cancer who had previously received 2 to 5 chemotherapy regimens. The endpoint definition makes clear what qualified as a response, and the record identifies the analysis population to which the percentage was intended to apply. However, the observed percentage and 95% confidence interval are not reported in the registry record. The primary efficacy result therefore cannot be summarized or judged for precision.

The completed status indicates that the study is recorded as completed; it does not supply a missing endpoint estimate. Likewise, a defined outcome and a stated analysis population do not establish what the study found. No inference about the frequency of response is warranted without the numerical result.

Even with a reported response estimate, a single-arm study would not provide a randomized comparison. The result would describe outcomes among participants treated in this study, rather than the difference attributable to eribulin compared with another treatment. Differences in participant characteristics, disease course, and outcome assessment would complicate comparisons with results from other studies.

The reported adverse-event counts add descriptive safety information but do not resolve these efficacy limitations. The registry record lists serious and other adverse events and deaths, without a comparator or detailed causal assessment in the registry record for this analysis. Those counts should not be taken as a complete account of benefit and risk or as proof that a particular event was caused by treatment.

The most defensible interpretation is consequently narrow: the registry record describes a Phase 2, open-label, single-arm study, specifies its response criteria and analysis population, and reports selected safety counts. It does not report the primary endpoint estimate, its precision, or comparative efficacy. It also does not supply enough detail to evaluate the statistical analysis plan, missing-data handling, or the two-stage decision process.

14. Why This Trial Matters Statistically

Statistically, this study illustrates why a clearly defined endpoint and a reported result are both necessary for interpretation. The record gives a structured definition of objective response under RECIST 1.1 and identifies an evaluable analysis set. Those details tell readers what the planned percentage represents. But without the observed percentage, its confidence interval, and the analysis denominator, the primary result cannot be evaluated for magnitude or precision.

The single-arm design also makes the scope of an estimate especially important. A within-group response rate can describe outcomes in the study population, but it cannot by itself quantify an effect relative to a control treatment. This distinction helps separate a descriptive clinical outcome from a comparative treatment effect. The open-label investigator assessment adds another consideration because knowledge of treatment can potentially influence outcome assessment in general, although the record does not establish that it did so.

The study’s stated 2-stage structure raises questions about how stages were managed and what rules guided continuation or stopping. Those features can affect interpretation of the analysis if they involve interim decisions, but the registry record does not report the relevant details. Statistical transparency requires more than a design label: readers need the decision rules, analysis methods, and outcome reporting to assess how the study proceeded.

Finally, the safety counts show why denominators, event definitions, follow-up, and attribution matter. Counts can convey what was recorded, but without a comparator they do not estimate relative safety. The record’s endpoint definitions and group counts are useful context, while the absent primary result and analysis details place firm limits on what can be inferred.

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 primary limitation for interpreting efficacy is that the objective response rate and its 95% confidence interval are not reported in the registry record. The number of participants in the evaluable analysis set is also not reported, preventing assessment of the analysis denominator or an independent check of the result.

The single-arm design has no concurrent control group, so it cannot estimate a randomized comparison or separate treatment-associated outcomes from other influences. The study was open-label, and the primary outcome was assessed by investigators. The record does not report whether an independent review or other safeguards were used to address possible assessment bias.

Although the study is described as 2-stage, its stage-specific enrollment rules, stopping criteria, and any interim analyses are not reported. The statistical analysis plan, confidence-interval method, hypothesis-testing procedures, and multiplicity approach are also not reported in the registry record. Missing-data handling beyond the stated evaluable-set definition is not reported.

The record lists selected safety counts, but the registry entries available for this analysis do not include detailed event timing, participant-level overlap, attribution, or a cause breakdown for deaths. These omissions limit causal and comparative interpretation of safety. The registry record also does not report numerical results for the listed secondary outcomes in the registry record.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Study to Evaluate the Efficacy and Safety of Eribulin Mesylate Administered Biweekly (Q2W) for Participants With Human Epidermal Growth Factor Receptor 2 (HER2)-Negative Metastatic Breast Cancer — NCT02481050.
• Registry record last updated 2018-11-15; status last verified 2018-01.
• Results first posted 2018-11-15.
• 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

This completed Phase 2 study evaluated biweekly intravenous eribulin mesylate at 1.4 mg/m2 in participants with HER2-negative metastatic breast cancer previously treated with 2 to 5 chemotherapy regimens. It was open-label, multicenter, and single-arm, with a stated 2-stage design and planned enrollment of 58.

The primary endpoint was investigator-assessed objective response rate under RECIST 1.1 in the evaluable analysis set. The registry record does not report the primary endpoint estimate, its 95% confidence interval, or the size of that analysis set. It lists secondary outcomes including progression-free survival, overall survival, feasibility, and adverse events, but their numerical results are not reported in the registry record for this analysis.

Selected safety counts are recorded, including 14 participants with serious adverse events among 58 at risk and 40 deaths. With no comparator and limited reporting detail, these are descriptive counts rather than comparative or causal estimates.