Brostallicin and Cisplatin in Treating Patients With Metastatic Breast Cancer: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Brostallicin and Cisplatin in Treating Patients With Metastatic Breast Cancer (NCT01091454), a na phase 2 study. The primary outcome is 3-month Progression-free Survival (3-mo PFS) Rate.

2. Clinical Question

3. Trial Design

This was a phase II, single-group trial of brostallicin and cisplatin for metastatic triple-negative breast cancer. The registry lists the Alliance for Clinical Trials in Oncology as sponsor, an enrollment of 48, and a completed status. The recorded start was 2010-06, and primary completion was 2012-06. These dates describe the registry record; they do not by themselves provide details about recruitment, follow-up, or the timing of individual assessments.

Participants in the treatment group were scheduled to receive cisplatin intravenously over 2 hours on day 1 and brostallicin intravenously over 10 minutes on day 2. Courses were to repeat every 21 days in the absence of progression or unacceptable toxicity. The design was unmasked, and allocation was listed as not applicable. Because there was only one group, the study was not a randomized comparison and has no concurrent control arm in the registry record.

The primary outcome was the 3-month progression-free survival rate. The record also lists confirmed response rate, duration of response, 6-month progression-free survival rate, time to disease progression, and survival time as secondary outcomes. Although the registry lists six outcome measures, numerical estimates for the primary endpoint are not reported in the registry record. The registry record lists no analyses.

A single-group phase II design can describe outcomes observed among participants receiving a regimen, but it cannot separate treatment effects from other explanations as directly as a randomized comparison. Differences in patient characteristics, disease course, assessment, or follow-up cannot be balanced against a contemporaneous control group within this design. No protocol details or additional statistical plan beyond the endpoint description are 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.

Overall Study

Reasons for not completing this period:

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 3-month Progression-free Survival (3-mo PFS) Rate, measured over 3 months.

The primary endpoint is the 3-month progression-free survival rate. A patient counts as a success under the registry definition if the patient is still on study treatment 3 months from registration and there is no documentation of disease progression. The endpoint is therefore a proportion at a specified time point, rather than a measure of average time until progression.

The registry defines progression using revised RECIST guideline version 1.1 criteria. It includes a 20% increase in the sum of the longest diameter of target lesions, a measurable increase in a non-target lesion, or the appearance of new lesions. For the target-lesion increase, the definition also requires an absolute increase of at least 5 mm.

A fixed-time proportion offers a clinically interpretable description of the share of evaluable patients meeting the endpoint at the stated time. It does not describe how long each patient remained progression-free beyond that time point, and it does not by itself show whether the regimen caused the observed outcome. The registry planned to estimate the proportion as successes divided by evaluable patients and to calculate a 95% confidence interval using the Duffy and Santner approach. If patients were lost to follow-up before they had been observed for at least 3 months, the endpoint description specifies a Kaplan-Meier estimate and confidence interval incorporating censoring. The estimate and interval are not reported in the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

What does a proportion estimate describe?

In general, a proportion is the number of participants meeting a specified outcome divided by the relevant analysis population. For this trial, the registry defines the primary outcome as the proportion of evaluable patients who were on study treatment 3 months from registration without documented progression. The numerator and denominator used in the actual analysis are not reported in the registry record, so the observed proportion cannot be reconstructed from the available record.

A proportion at a fixed time point is different from a time-to-event estimate. The proportion answers whether patients met the endpoint at the specified time, according to the endpoint definition. Time-to-event methods use the timing of events and can account for follow-up ending before an event is observed. The registry describes a Kaplan-Meier approach if some patients were lost to follow-up without being observed for at least 3 months.

What does a confidence interval add?

In general, a confidence interval expresses uncertainty around an estimate. It helps readers judge how precisely a proportion has been estimated, rather than treating the point estimate as exact. A wider interval indicates greater uncertainty than a narrower interval. The registry planned 95% confidence intervals for the primary proportion using the approach of Duffy and Santner. Neither the interval nor the point estimate is reported in the registry record, so the precision of the trial’s primary result cannot be assessed from the posted information.

Why might censoring matter?

In general, censoring occurs when a participant’s event status or time to event is not fully observed during follow-up. A participant who has not been followed for the full period cannot simply be assumed to have remained progression-free throughout that period. The registry endpoint description anticipates this issue: if patients were lost to follow-up before at least 3 months of observation, the planned estimate and confidence interval would incorporate censoring using Kaplan-Meier methods.

Kaplan-Meier estimation uses the timing of observed events and the follow-up available for participants who have not yet had an event. Its interpretation relies on assumptions about the censoring process. In general, results can be difficult to interpret if people who leave observation differ in their event risk from those who remain under observation. The registry record does not say whether censoring occurred, how many participants were censored, or whether the planned method was used in the final analysis.

How is progression defined?

The registry uses revised RECIST guideline version 1.1 criteria. Its description includes a 20% increase in the sum of the longest diameter of target lesions, a measurable increase in a non-target lesion, or the appearance of new lesions. For the target-lesion increase, the sum must also show an absolute increase of at least 5 mm. In general, a prespecified definition helps make outcome classification more consistent. The registry record does not provide assessment schedules, details about independent review, or information about how progression was adjudicated.

What can a single-group design establish?

In general, a single-group study can describe outcomes and safety events observed in the group receiving treatment. It does not directly estimate a contrast against a concurrent control group. Without random assignment to different groups, observed outcomes cannot be separated as confidently from background disease course, patient selection, or other influences. This trial is listed as single-group, with allocation not applicable and no masking. The registry record does not report a randomized comparison.

The registry record lists no analyses. It gives the primary endpoint’s planned estimation methods, but does not report the numerical output needed to evaluate the primary estimate. The record also does not report an adjusted analysis, a statistical model for covariates, or details about interim analyses. Such information should not be inferred from the endpoint description alone.

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("Treatment (Cisplatin and Brostallicin)")
n      <- c(47)
events <- c(0)
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  Treatment (Cisplatin and Brostallicin)  47  0  0.0  0.0  7.5  0.0  7.6  0.1  7.4

11. Multiplicity, Missing Data and Analysis Populations

The registry lists a primary endpoint and secondary outcomes including confirmed response rate, duration of response, 6-month progression-free survival rate, time to disease progression, and survival time. When a study examines multiple outcomes, the chance of obtaining at least one apparently notable result can increase if many statistical tests are performed. In general, multiplicity methods may address that issue, but the registry record does not report a multiplicity adjustment, testing hierarchy, or statistical plan for interpreting secondary outcomes. It lists no analyses, and numerical results for the primary endpoint are not reported in the registry record.

The primary endpoint description identifies evaluable patients as the denominator for the planned proportion. It also describes a Kaplan-Meier approach if patients were lost to follow-up before being observed for at least 3 months. However, the criteria for evaluability, the number included in the primary analysis, the amount of missing follow-up, and the final handling of missing endpoint information are not reported in the registry record.

In general, missing outcome data can affect an estimate if participants with missing results have different outcomes from those with observed results. Censoring methods use available follow-up, but their interpretation depends on assumptions about why follow-up ended. The registry describes the intended response to a specified loss-to-follow-up situation; it does not provide enough information to assess the extent of missing data or whether those assumptions were plausible in this trial.

The registry enrollment is 48, but that figure should not be treated as the primary endpoint denominator: the endpoint description specifies evaluable patients, and the actual analysis population is not reported. Reasons for exclusions, withdrawals, and treatment discontinuation are also not reported in the registry record.

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: platelet count decreased (41.7%), neutrophil count decreased (39.6%), febrile neutropenia (14.6%), white blood cell decreased (10.4%), anemia (8.3%).

The registry reports serious adverse events affecting 29 participants among 48 at risk in the treatment group. It separately reports other adverse events affecting 48 participants among 48 at risk. These are descriptive counts from a single treatment group, not estimates of a difference versus a control group. The record does not report an adverse-event comparison with another regimen.

The listed serious adverse event terms include platelet count decreased at 41.7%, neutrophil count decreased at 39.6%, febrile neutropenia at 14.6%, white blood cell decreased at 10.4%, anemia at 8.3%, and fatigue at 6.2%. These percentages should be interpreted as the registry’s reported figures for the listed terms; the record does not give event counts for each term or further details about grading, duration, or recurrence.

General cautions apply when interpreting adverse-event summaries: a participant may experience more than one type of event, and participant-level counts do not necessarily equal event-level counts. The registry record does not provide the observation period, the specific criteria used to classify serious events, or detailed information about attribution to treatment. The data describe reported events in the study group; they do not establish comparative risk or causation.

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

The primary endpoint was designed to describe the proportion of evaluable patients who remained on study treatment at 3 months from registration without documented progression. The registry provides a definition and planned methods for estimating this rate, including an approach for censoring if patients were lost to follow-up before sufficient observation. However, the numerical estimate, its 95% confidence interval, and the analyzed population are not reported in the registry record.

As a result, the posted information does not show how large the observed 3-month rate was or how precisely it was estimated. It also does not support a conclusion that the combination did or did not improve outcomes. The single-group design has no concurrent comparator, so outcomes in the treatment group cannot be directly contrasted with outcomes under another treatment or control condition.

The record does establish the trial’s context: a completed phase II study, a single treatment group, the scheduled cisplatin and brostallicin regimen, and a primary endpoint defined around progression-free status at a fixed time. It also reports safety counts and selected serious adverse event percentages. These are descriptive observations and should not be interpreted as comparative evidence.

More broadly, a planned endpoint definition is not itself a result. Interpretation of an observed proportion would require its estimate, uncertainty interval, analysis population, and information about missing observations. In a single-group study, even a clearly estimated rate would describe what was observed in the study population rather than isolate a treatment effect. The registry record does not report enough numerical efficacy information to make that assessment.

14. Why This Trial Matters Statistically

This trial illustrates an important distinction between an endpoint’s statistical plan and its reported result. The registry defines the 3-month progression-free survival rate, specifies the endpoint population as evaluable patients, and describes a confidence-interval method. It also anticipates a possible follow-up problem and names Kaplan-Meier estimation as the approach if patients were lost before at least 3 months of observation. These details help explain how the primary outcome was intended to be measured.

At the same time, the registry record does not report the primary estimate, its confidence interval, or the analysis population. Without those elements, the central statistical result cannot be assessed for magnitude or precision. The record lists no analyses, emphasizing that an endpoint definition and a numerical result are separate parts of the evidence needed for interpretation.

The design also demonstrates why comparison structure matters. A single-group study can characterize outcomes and reported safety events among people receiving a regimen, but has no concurrent control against which to estimate a treatment contrast. This distinction remains important even when an endpoint is clearly specified and measured with a recognized statistical method.

Finally, the safety summaries show why denominators and event definitions matter. The record reports participant counts affected by serious and other adverse events, and percentages for selected serious-event terms, but does not include detailed event-level information or a comparison group. Careful interpretation requires keeping descriptive reporting distinct from comparative inference. These are broadly useful statistical lessons for clinical researchers reading registry records.

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 for interpreting efficacy is that the registry record does not report the numerical primary endpoint result. The 3-month progression-free survival estimate, its 95% confidence interval, and the number of evaluable patients are not reported. Although enrollment is listed as 48, that figure is not identified as the primary analysis denominator.

The endpoint depends on remaining on study treatment and having no documented progression at the stated time. The record does not report how participants who stopped treatment for other reasons were classified, whether all patients had adequate follow-up, or how many were lost to follow-up. It describes a method for censoring but does not report whether that method was needed or applied.

The design was single-group and unmasked, with allocation listed as not applicable. There is no randomized control group for a direct treatment comparison. The registry record does not report further eligibility criteria, assessment schedules, independent review procedures, protocol deviations, or reasons for treatment discontinuation. These omissions limit assessment of who entered the analysis and how consistently outcomes were measured.

The safety record provides counts and selected percentages, but does not report the adverse-event observation period, grading details, event-level counts for the listed terms, or comparative safety information. The registry record also does not report a multiplicity plan, a detailed statistical analysis plan, or interim analysis information. These limitations concern what can be learned from this record and should not be filled in by assumptions.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Brostallicin and Cisplatin in Treating Patients With Metastatic Breast Cancer — NCT01091454.
• Registry record last updated 2018-05-08; status last verified 2018-04.
• Results first posted 2017-03-20.
• 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 describes a completed phase II, single-group trial of brostallicin and cisplatin in metastatic triple-negative breast cancer. Enrollment was 48. The regimen scheduled cisplatin intravenously on day 1 and brostallicin intravenously on day 2, with courses repeating every 21 days absent progression or unacceptable toxicity.

The primary endpoint was the 3-month progression-free survival rate among evaluable patients. The record describes the endpoint definition and planned methods, but the observed estimate, confidence interval, and analysis population are not reported in the registry record. The registry lists no analyses.

Safety reporting includes serious adverse events affecting 29 participants among 48 at risk and other adverse events affecting 48 participants among 48 at risk. Selected serious adverse event terms and percentages are listed, but the record does not provide detailed event-level or comparative safety results. The single-group design supports descriptive interpretation, not a randomized treatment comparison.