Phase II Study Of E7389, Halichondrin B Analogue, In Patients With Advanced Non-Small Cell Lung Cancer, NSCLC, Who Progressed During Or After Platinum-Based Doublet Chemotherapy: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Phase II Study Of E7389, Halichondrin B Analogue, In Patients With Advanced Non-Small Cell Lung Cancer, NSCLC, Who Progressed During Or After Platinum-Based Doublet Chemotherapy (NCT00100932), a non-randomized phase 2 study. The primary outcome is Overall Objective Response Rate (ORR).

2. Clinical Question

The study record identifies a Phase II evaluation in patients with advanced NSCLC after progression during or after platinum-based doublet chemotherapy. Its stated focus is tumor response to E7389, rather than a randomized comparison against another treatment. Duration of response, progression-free survival, and overall survival are listed as secondary outcomes, but their results are not reported in the registry record. The record also does not give a primary-outcome estimate, confidence interval, or analysis comparing the schedules. Accordingly, the clinical question can be described from the intended population, treatment schedules, and endpoint definition, but the posted registry information does not answer it with a numerical efficacy result.

3. Trial Design

This is a completed Phase II study of E7389 in people with advanced NSCLC whose disease progressed during or after platinum-based doublet chemotherapy. The registry lists enrollment of 106 and describes two parallel arms: E7389 on a 28-day cycle and E7389 on a 21-day cycle. Allocation is recorded as non-randomized, and masking as none. The two schedules are not randomized treatment groups, so any contrast between them could reflect differences in the participants or other features of how treatment was assigned, as well as differences associated with schedule.

The study began in 2004-12, reached primary completion in 2008-06, and is marked completed. The registry's official title describes stratification for prior taxane therapy. However, details of the stratification process, including how it was implemented and what results were observed within strata, are not reported in the registry record. It is not possible to infer that this created comparable groups or to determine how prior taxane therapy was handled in the analysis.

Overall objective response rate is the primary outcome. The record defines it as the best response from the start of treatment until disease progression or recurrence, using RECIST and imaging by CT and MRI. Duration of response, progression-free survival, and overall survival are named as secondary outcomes. Although four outcome measures are recorded, outcome values and analysis results are not reported in the registry record. The number of analyses recorded is zero.

The record identifies an Intent to Treat/Safety Population for the primary outcome, but does not explain the membership rules or how missing response assessments were handled. Further protocol details, such as eligibility criteria beyond the stated disease and treatment history, treatment administration, follow-up procedures, and the statistical analysis plan, are not reported in the registry record. These omissions limit how fully the trial conduct and its outcome estimates can be evaluated.

4. Participant Flow and Accounting

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

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: Intent to Treat/Safety Population

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 Overall Objective Response Rate (ORR), measured over From start of treatment until disease progression or recurrence.

Overall objective response rate (ORR) is the percentage of participants whose best recorded tumor response is a complete response or partial response. The registry defines complete response as disappearance of all lesions and partial response as a 30% decrease in lesion diameter. It also describes progressive disease as a 20% increase in lesion diameter and stable disease as neither shrinkage nor increase. Response is assessed using RECIST, with lesions measured by CT and MRI.

The outcome is evaluated from the start of treatment until disease progression or recurrence. Using the best response over this interval is intended to capture whether a participant experienced a qualifying tumor reduction during treatment, rather than relying on a single assessment. In general, response rate is a binary outcome at the participant level: each person is classified according to whether a complete or partial response was recorded. The corresponding percentage depends on both the number classified as responders and the defined analysis population.

Response rate is used in clinical trials as a direct measure of observed tumor shrinkage under specified assessment criteria. It does not, by itself, describe how long a response lasts, how long participants live without progression, or overall survival. The registry lists duration of response, progression-free survival, and overall survival separately as secondary outcomes. It does not report the ORR count or percentage, so the magnitude and precision of the primary endpoint cannot be assessed from the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The primary outcome is a binary participant-level response classification. Under the registry definition, a participant is counted as having an objective response if the best response is complete response or partial response. In general, a response percentage summarizes the proportion of a specified population meeting that definition. Interpreting such a percentage requires knowing both the response count and the population included in the calculation. The record names the Intent to Treat/Safety Population, but does not report the response count or percentage.

What does the endpoint definition contribute?

RECIST provides a standardized way to classify changes in measurable lesions. The registry describes complete response as disappearance of all lesions, partial response as a 30% decrease in lesion diameter, progressive disease as a 20% increase, and stable disease as neither shrinkage nor increase. CT and MRI are named as imaging methods. Standardized definitions can make assessments more consistent, but the registry record does not provide details about assessment schedules, independent review, or how disagreements between assessments were resolved. Those methods are not reported in the registry record.

The endpoint uses the best response from treatment start until progression or recurrence. In general, a best-response outcome records whether a participant met the response criterion at any qualifying assessment during the specified interval. It is distinct from a response measured at one fixed visit and from time-to-event outcomes such as progression-free survival. The record does not report how participants without an evaluable follow-up assessment were classified, or what rules were applied to incomplete or missing imaging.

How should uncertainty be considered?

A confidence interval is a statistical range that conveys uncertainty around an estimate under the assumptions of the analysis. For a response percentage, its width is affected by the amount of available information and the observed response pattern. A narrow interval generally indicates greater precision than a wide interval, although precision is not the same as freedom from bias. The registry record does not report an ORR confidence interval or a response estimate, so its precision cannot be assessed from the posted results.

For a comparison between schedules, random assignment is commonly used to support comparability of treatment groups. Here, allocation is recorded as non-randomized. In general, non-randomized groups may differ before treatment, and those differences can complicate interpretation of an observed contrast. Statistical adjustment can address measured differences under suitable assumptions, but cannot guarantee control of unmeasured differences. The registry record does not report an adjusted analysis, an unadjusted arm comparison, or the methods used to assign treatment. Its design therefore does not justify treating the schedule arms as a randomized comparison.

What does the planning illustration mean?

The sample-size assumptions describe a planning illustration based on an observed effect, with a two-sided significance level of 0.05, equal allocation between arms, and a normal approximation. The effect to detect is expressed as a stated fraction of the observed effect. These are assumptions for an illustration, not evidence about the study's original design. The record does not report the trial's own sample-size justification, and the effect estimate on which the illustration is based is not reported in the registry record. Any resulting sample-size values are planning illustrations, not observed power and not evidence that the trial was adequately or inadequately sized.

In general, a planned sample size depends on the outcome, effect being targeted, variability or event frequency, significance level, power target, allocation, and analysis method. Changing the assumed effect changes the planning requirement. For a binary response outcome, the event frequency matters to the uncertainty of a percentage and to a comparison of percentages. The record does not give the ORR data needed to independently judge those assumptions. Planning calculations should therefore not be mistaken for observed trial findings.

How should the safety counts be understood?

The safety record gives, for each schedule group, the number at risk for serious adverse events and the number affected by at least one such event. It also gives counts at risk and affected for other adverse events. These are descriptive counts. In general, an event proportion uses the affected count relative to the relevant population at risk; it is important to retain the registry's stated group and event definitions. Such a proportion does not by itself establish causation. The serious-event terms are listed with percentages, but the record does not provide enough detail to infer a comparative risk or attribute individual events to treatment.

Overall, the registry's methods information supports explaining how ORR is defined and what the non-randomized design implies. It does not support reconstructing response estimates, uncertainty intervals, a comparative treatment effect, or the full analysis strategy. Protocol details and statistical methods not explicitly described are not reported in the registry 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("E7389 28 Day Cycle", "E7389 21 Day Cycle")
n      <- c(77, 26)
events <- c(9, 1)
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  E7389 28 Day Cycle  77  9  11.7  5.5  21.0  6.3  20.7  6.3  20.8
ARM  E7389 21 Day Cycle  26  1  3.8  0.1  19.6  0.7  18.9  0.9  19.0

11. Multiplicity, Missing Data and Analysis Populations

The registry lists overall objective response rate as the primary outcome and names duration of response, progression-free survival, and overall survival as secondary outcomes. It records four outcome measures, but does not report numerical results for them. The number of analyses recorded is zero. The registry record does not describe whether formal hypothesis tests were planned, which outcomes were included in any testing sequence, or whether adjustment for multiple comparisons was used. Multiplicity procedures are therefore not reported in the registry record.

In general, testing multiple outcomes or making multiple comparisons can increase the chance of at least one apparently positive result if the analyses are interpreted without accounting for that multiplicity. This general concern does not establish that such testing occurred in this study. The analysis plan and any adjustment strategy are not reported, so the extent to which multiplicity is relevant to the trial's conclusions cannot be determined.

The named primary population is the Intent to Treat/Safety Population. The record does not define the population membership or explain whether the same participants were included in both efficacy and safety summaries. It also does not report the handling of missing response assessments, withdrawals, or participants without a usable post-baseline evaluation. In general, excluding participants with missing outcomes can affect an estimated response percentage if missingness is related to response or prognosis. No specific missing-data method can be attributed to this study from the registry record.

Consequently, neither the impact of missing data nor the relationship between the stated analysis population and the reported safety counts can be fully evaluated. The record does not report a detailed statistical analysis plan, sensitivity analyses, or outcome-level analysis results.

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 5% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: deep vein thrombosis (11.5%), dyspnea (7.7%), respiratory failure (7.7%), disease progression (6.5%), malignant neoplasm progression (5.2%).

For serious adverse events, the registry reports 77 at risk and 33 affected in the E7389 28 Day Cycle group, and 26 at risk and 11 affected in the E7389 21 Day Cycle group. These counts describe participants in the registry's safety reporting; they do not by themselves establish that an event was caused by E7389. The record also reports the at-risk and affected counts for other adverse events, with all participants in each group listed as affected.

The registry lists Deep Vein Thrombosis at 11.5%, Dyspnea at 7.7%, Respiratory Failure at 7.7%, Disease Progression at 6.5%, Malignant Neoplasm Progression at 5.2%, and Pyrexia at 3.9% among the top serious-event terms. These percentages should be read as the registry's reported figures, not as a comparison between schedules. The record does not specify a denominator alongside each listed term or provide enough detail to determine how event-term percentages were calculated.

In general, serious adverse events and common adverse events are different summaries, and one participant may experience more than one event. Counts and percentages are descriptive and can be affected by the population observed and duration of observation. Because allocation was non-randomized, differences between the schedule groups would not constitute a randomized safety comparison. The record does not report deaths in the adverse-event group summaries.

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

The study record establishes that E7389 was evaluated in a Phase II study of people with advanced NSCLC after progression during or after platinum-based doublet chemotherapy. It describes two dosing schedules and identifies overall objective response rate as the primary endpoint. It also specifies a RECIST-based response definition and lists secondary outcomes. These details clarify what the study intended to assess.

They do not establish the observed response rate. The registry record does not report the primary outcome count or percentage, and it does not provide a confidence interval or analysis result. The listed secondary outcomes likewise have no reported numerical results. Without those results, the posted information cannot quantify tumor response, response duration, progression-free survival, or overall survival.

The trial was non-randomized and unmasked. The two schedule groups are therefore not a like-for-like randomized comparison. Even if a difference between groups were reported, interpreting it as an effect of schedule would require attention to how participants entered each group and to possible differences in their characteristics. The registry record does not describe assignment methods or report an adjusted analysis. The title's reference to prior taxane stratification does not supply those missing details.

The serious adverse event counts and listed terms provide descriptive safety information. They do not, on their own, show that E7389 caused an event or establish comparative safety between schedules. The registry record does not report deaths in the adverse-event group summaries.

In general, a trial's outcome definition, study design, estimate, and uncertainty all contribute to interpretation. Here, the design and definitions are available, but the primary efficacy estimate and its uncertainty are not reported. Thus, the registry record can be used to understand what was studied and how response was defined, but it does not support a conclusion about the magnitude or precision of efficacy outcomes or a causal comparison of the dosing schedules.

14. Why This Trial Matters Statistically

This study is statistically informative as an example of why endpoint definitions and study design must be considered alongside results. Overall objective response rate is defined using RECIST categories and a specified period from treatment start until progression or recurrence. That definition identifies what would count as response, but without the response count or percentage it cannot quantify the endpoint. A clear measure is not a substitute for a reported estimate.

The design also matters for comparisons. The record describes parallel E7389 schedules, yet allocation was non-randomized. In general, randomization helps balance measured and unmeasured baseline factors in expectation; without it, a difference between groups can reflect treatment assignment patterns or participant characteristics. The title's reference to prior taxane stratification is relevant context, but the registry does not report how stratification was implemented or incorporated into analysis. This makes it important not to interpret the arms as randomized control groups.

The record further illustrates the distinction between efficacy and safety reporting. Serious adverse event counts and listed event terms are available, while the primary efficacy result is not. Each type of information answers a different question, and descriptive safety counts do not replace response estimates or demonstrate causation.

Finally, planning calculations and observed findings serve different purposes. The sample-size assumptions describe an illustration based on an observed effect, but are not the trial's own design justification and do not represent observed power. Keeping planning assumptions separate from trial results is essential, particularly when the underlying response estimate and analysis plan are not reported in the registry record. Together, these features make the study useful for careful discussion of what a registry record can and cannot support statistically.

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 consequential limitation of the registry record for interpreting efficacy is that it does not report the primary ORR count or percentage. It also provides no confidence interval or analysis result. Although it defines response criteria and the assessment interval, the observed frequency and precision of response cannot be assessed.

The non-randomized allocation limits comparison of the 28-day and 21-day schedules. The registry does not report how treatment schedule was assigned, whether participant characteristics differed between arms, or whether any adjustment was made. The official title mentions stratification for prior taxane therapy, but its implementation and associated results are not reported in the registry record. The two arms should therefore not be treated as a randomized comparison.

Important outcome-assessment details are also absent. The registry does not report assessment timing, independent review procedures, missing-assessment rules, or the handling of participants without evaluable response data. It names the Intent to Treat/Safety Population but does not define its membership. These omissions prevent evaluation of how the endpoint definition was applied in practice.

Although secondary outcomes are listed, their results are not reported. The registry record also does not describe multiplicity control, a full statistical analysis plan, or the trial's sample-size justification. The planning assumptions are an illustration and cannot fill these gaps. Safety reporting includes serious-event counts and selected terms, but event-term denominators and comparative analyses are not reported. These limitations restrict conclusions to the study's stated design, endpoint definitions, and descriptive safety information.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Phase II Study Of E7389, Halichondrin B Analogue, In Patients With Advanced Non-Small Cell Lung Cancer, NSCLC, Who Progressed During Or After Platinum-Based Doublet Chemotherapy — NCT00100932.
• Registry record last updated 2012-03-27; status last verified 2012-03.
• Results first posted 2012-01-31.
• 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

NCT00100932 is a completed Phase II, parallel, non-randomized, unmasked study of E7389 in people with advanced NSCLC whose disease progressed during or after platinum-based doublet chemotherapy. Enrollment is listed as 106. The arms received E7389 on a 28-day cycle or a 21-day cycle. Overall objective response rate was the primary outcome, defined using RECIST as complete response plus partial response from treatment start until progression or recurrence. Duration of response, progression-free survival, and overall survival are listed as secondary outcomes.

The registry record does not report the primary response result, secondary outcome results, or analysis results. Serious adverse event counts are reported for each schedule, along with selected serious-event terms and percentages. Because allocation was non-randomized, the arms are not a like-for-like control comparison. The record supports a description of the design, outcomes, and safety reporting, but not a quantitative efficacy assessment or a causal comparison of schedules.