Gemcitabine/ Trastuzumab and Gemcitabine/ Cisplatin/ Trastuzumab in Patients With Metastatic Breast Cancer: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Gemcitabine/ Trastuzumab and Gemcitabine/ Cisplatin/ Trastuzumab in Patients With Metastatic Breast Cancer (NCT00201760), a randomized phase 2 study. The primary outcome is Disease Progression.

2. Clinical Question

The trial asked whether the number of participants with metastatic breast cancer who remained free of disease progression at 6 months differed between two drug combinations. One combination paired gemcitabine with trastuzumab; the other added cisplatin to those drugs. The registry record describes a randomized phase II study and lists 10 participants overall.

The posted results report 1 participant for the gemcitabine/cisplatin/trastuzumab group and 0 for the gemcitabine/trastuzumab group on this outcome; each group had 5 participants. These are small counts, so the observed difference in counts is not, by itself, a precise estimate of how the groups would compare in a broader population. The registry record does not report a statistical test or an estimated treatment contrast for the primary outcome.

The study also listed response rate and grade 3 and grade 4 toxicity profiles as secondary outcomes. The registry record does not report results for those outcomes. The central question is therefore narrower than a general comparison of tumor response, safety, or overall clinical benefit: it concerns the recorded 6-month disease-progression status.

3. Trial Design

This was a randomized, parallel-group phase II study with no masking. The registry record lists 10 participants and reports 5 participants in each treatment group. The study status is completed. The recorded start date is 2005-02-25, and the primary completion date is 2009-10-31.

Arm 1 received gemcitabine, cisplatin, and trastuzumab. Arm 2 received gemcitabine and trastuzumab. Because masking was listed as none, the registry record describes an unmasked trial. Details about how the randomization sequence was generated, whether allocation was concealed, or how treatment assignment was communicated are not reported in the registry record. The specific study sites and participant recruitment details are also not reported in the registry record.

A parallel-group design assigns participants to one treatment group and follows those groups as distinct arms. Randomization is intended, in general, to reduce systematic differences between groups at assignment. With 5 participants in each group, chance differences in participant characteristics can still be substantial; the registry record does not provide baseline characteristics that would allow those differences to be assessed.

The primary outcome was the number of participants free of disease progression at 6 months following treatment. The registry record also lists response rate and grade 3 and grade 4 toxicity profiles as secondary outcomes. It does not report detailed endpoint definitions, assessment procedures, or the schedule and methods used to determine disease progression. Details about treatment discontinuation, adherence, or post-treatment follow-up are not reported in the registry record.

The registry record does not report a planned sample-size justification, a prespecified statistical analysis plan, or interim analyses. It also does not report the analysis population used for the primary outcome. Those omissions limit the ability to determine whether the posted outcome counts reflect all randomized participants, only participants with available follow-up, or another analysis set.

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

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 Disease Progression, measured over 6 months.

The primary endpoint concerns disease progression at 6 months. Its description is the proportion of participants with metastatic breast cancer who were free of disease progression at that time following treatment. The posted outcome is expressed as participant counts: 1 for the gemcitabine/cisplatin/trastuzumab group and 0 for the gemcitabine/trastuzumab group, with 5 participants recorded in each group.

A fixed-time disease-progression endpoint offers a direct way to describe how many participants meet a clinically relevant disease-status condition at a specified follow-up point. In general, a fixed-time measure can be easier to interpret than a summary that combines outcomes across different follow-up durations, provided that the outcome definition and follow-up status are clear. The registry record does not report the assessment criteria used to determine progression, how deaths or missing assessments were handled, or whether participants were assessed at the same time point.

The endpoint is a count rather than a complete presentation of a comparative effect estimate. It does not, on its own, describe uncertainty around the difference between treatment groups. No confidence interval or statistical test for the primary outcome is reported in the registry record. Since there were 5 participants in each group, the counts represent a very limited amount of outcome information. The endpoint should be read as a description of the posted observations, not as a precise estimate of the treatment effect or as a basis for conclusions beyond this trial.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The trial’s primary outcome is binary: at the 6-month assessment, a participant is described as free of disease progression or not. The posted outcome is a count of participants in each treatment group who meet the stated condition. A count gives the observed number of participants with the outcome; an estimate of the underlying probability would also need to account for uncertainty, especially when the group is small.

What does randomization contribute?

In general, randomization assigns treatment by chance rather than by clinical choice. Its purpose is to reduce systematic differences between treatment groups at the time of assignment. Randomization does not guarantee that groups will have similar characteristics in a small trial. Baseline characteristics and details of sequence generation and allocation concealment are not reported in the registry record, so the success and implementation of randomization cannot be evaluated from those details.

The study is listed as randomized, parallel, and unmasked. In a parallel design, participants remain in their assigned treatment groups for the group comparison rather than crossing between regimens. No masking means that blinding is not listed in the registry record. In general, lack of masking can matter for outcomes involving judgment or reporting, but the registry record does not describe how progression assessments were conducted or whether assessors were independent of treatment assignment.

How should a binary outcome be compared?

For a binary outcome, analysis may describe the count and proportion in each group and estimate a contrast between those groups. The contrast could be expressed in different ways, but the registry record does not report a comparative effect estimate for the primary endpoint. It also does not report a confidence interval or statistical test. Therefore, the posted counts alone do not quantify the precision of the group comparison.

In general, a confidence interval gives a range of values that are reasonably compatible with the data and a stated statistical procedure. A narrow interval indicates greater precision than a wide interval. With few participants and sparse outcome counts, estimates can be imprecise, and standard approximations may be unreliable. The registry record does not report an interval estimate or the method that would have been used to calculate one. No interval should be inferred from the participant counts alone in this interpretation.

In general, a p-value assesses how unusual the observed data would be under a specified null hypothesis and statistical model. It does not measure the size or clinical importance of an effect, and it does not provide the probability that the null hypothesis is true. No primary-outcome p-value or test is reported in the registry record. The absence of a reported test should not be replaced with a test reconstructed from the posted counts as though it were the sponsor’s planned analysis.

What does over-dispersion mean?

Over-dispersion is a general issue for count outcomes when the observed variability exceeds what a chosen statistical model expects. It can make model-based uncertainty too small if ignored. The primary outcome in this trial is presented as a count of participants with a binary status, not as a repeated event count with a reported dispersion estimate. Dispersion is not reported in the registry record, and no model-based analysis is reported. Over-dispersion therefore cannot be assessed from the posted primary outcome summary.

What can planning calculations say?

The registry record describes sample-size illustrations based on the observed effect, a two-sided significance level of 0.05, equal allocation, and a normal approximation. The effect to detect is described as a stated fraction of the observed effect. In general, a planning calculation asks how many participants might be needed under specified assumptions to detect a target effect with a chosen level of power. Such illustrations are not observed power, do not show that the trial had adequate power, and do not establish that the target effect is realistic. They are especially dependent on the observed effect when that estimate comes from a small trial. The registry record does not report its own sample-size justification.

For binary outcomes with very small groups or sparse counts, the normal approximation may be a poor fit; alternative methods can be considered in general. The registry record does not report a method selected for a comparative analysis, so no particular approach can be attributed to this trial. The posted results also state that a two-arm comparison was not estimable for the binary endpoint. Accordingly, no comparative value should be read into a missing analysis.

The registry record lists zero analyses. This means no analysis result is posted for the primary comparison in the record; it does not establish what analyses may or may not have been performed outside the registry. Details about model adjustment, covariates, handling of multiple outcomes, and sensitivity analyses 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("Arm 1 Gemcitabine/Cisplatin/Trastuzumab", "Arm 2 Gemcitabine / Trastuzumab")
n      <- c(5, 5)
events <- c(1, 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  Arm 1 Gemcitabine/Cisplatin/Trastuzumab  5  1  20.0  0.5  71.6  3.6  62.4  4.3  64.1
ARM  Arm 2 Gemcitabine / Trastuzumab  5  0  0.0  0.0  52.2  0.0  43.4  0.4  45.9

11. Multiplicity, Missing Data and Analysis Populations

The registry record lists two secondary outcomes: response rate for each drug combination and the number of participants with grade 3 and grade 4 toxicity profiles. It does not report results for these secondary outcomes. The primary outcome is disease progression at 6 months. The record does not describe a hierarchy for testing outcomes, an adjustment for multiple comparisons, or whether the primary outcome was designated before the data were examined. These matters are not reported in the registry record.

In general, when several outcomes or comparisons are tested, the chance of at least one apparently unusual result can increase if each is assessed separately. Prespecified outcome priorities and multiplicity procedures can help readers understand how to interpret a collection of tests. No such procedure is reported for this trial, and no set of statistical tests is posted. It is therefore not possible to assess multiplicity-adjusted evidence from the registry record.

Missing-data handling is also not reported in the registry record. The record does not state whether all randomized participants had a 6-month assessment, how missing progression status was treated, or whether any participants were excluded from the primary analysis. The analysis population is not reported in the registry record. Although the arm summaries list 5 participants in each group, those counts alone do not document the follow-up completeness or analysis rules.

In general, the handling of missing outcome information can affect a binary endpoint, particularly when the outcome depends on status at a specified follow-up time. Different assumptions about participants with unknown status can lead to different estimates. No imputation method, sensitivity analysis, or missingness summary is reported in the registry record. The available record therefore does not support conclusions about the robustness of the primary result to missing data.

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 5% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: pneumonia (20.0%), nausea/vomiting/diarrhea (20.0%).

The registry lists serious adverse events affecting 1 participant in the gemcitabine/cisplatin/trastuzumab group and 0 participants in the gemcitabine/trastuzumab group. Each group lists 5 participants at risk. The registry also lists other adverse events affecting 5 participants in each group, with 5 participants at risk in each group. These are participant counts and should be read separately from the primary disease-progression outcome.

Pneumonia and nausea/vomiting/diarrhea are listed among the leading serious adverse event terms, each at 20.0%. The registry record does not provide further detail about event timing, severity beyond the serious classification, recurrence, or attribution to treatment. It also does not state which treatment group contributed each listed term, so those terms should not be assigned to an arm based on the aggregate listing.

The record lists 1 death in the gemcitabine/cisplatin/trastuzumab group and 0 in the gemcitabine/trastuzumab group. It does not report the causes of death or whether deaths were considered related to treatment. These small counts are descriptive; they do not establish a comparative safety rate. As with the efficacy outcome, limited group sizes make the counts imprecise, and the registry does not report a statistical comparison for safety outcomes.

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

The posted results describe what was recorded among the participants in this randomized phase II study: 1 participant in the gemcitabine/cisplatin/trastuzumab group and 0 in the gemcitabine/trastuzumab group were reported free of disease progression at 6 months. There were 5 participants in each group. These observations are the trial’s posted primary outcome counts, not a precise estimate of the outcome in a broader population.

The counts do not establish that adding cisplatin changes the chance of being free of progression. They also do not establish equivalence between the combinations. A comparison would need an effect estimate and an assessment of uncertainty; neither is reported for the primary outcome in the registry record. Sparse data from a small trial leave substantial uncertainty about the range of effects compatible with the observed counts.

The result also does not answer broader questions about response, duration of disease control, quality of life, or overall benefit. Response rate is listed as a secondary outcome, but its result is not reported in the registry record. The record does not provide enough detail about progression assessment and follow-up to evaluate all aspects of the endpoint’s measurement. Safety summaries are separate observations and likewise do not prove a causal relationship between treatment and an event.

In general, a randomized design can support a fair comparison when it is implemented and analyzed appropriately, but randomization alone does not remove uncertainty created by limited enrollment, incomplete reporting, or missing outcome information. The registry record does not report a sample-size justification, analysis population, missing-data method, or primary statistical test. These gaps make it difficult to judge how the posted analysis was planned and how sensitive it might be to analytic choices.

The appropriate interpretation is narrow: the registry records different observed counts for the two groups on the 6-month endpoint, but does not report a comparative statistical analysis that would establish the size or precision of a treatment effect. No medical recommendation follows from these results.

14. Why This Trial Matters Statistically

This trial illustrates how a randomized design and a small enrollment can coexist. Randomization provides a framework for comparing assigned treatment groups, but the registry lists only 10 participants, with 5 in each arm. At this scale, each participant’s outcome has considerable influence on the group summary. The primary outcome counts are therefore best understood as descriptive observations with substantial uncertainty.

It also illustrates the difference between an outcome count and an inferential comparison. A count reports how many participants met the stated condition. A treatment-effect estimate and its uncertainty would help readers assess the magnitude and precision of a group contrast. The registry record does not report those comparative statistics for the primary endpoint. Consequently, the apparent contrast in the posted counts cannot be treated as conclusive evidence of a difference.

The record is also a reminder that registration information and outcome reporting do not always answer the same questions. The primary endpoint is described, but detailed progression criteria, missing-data handling, analysis populations, and statistical methods are not reported in the registry record. Such details matter because they explain how an endpoint was measured and how observed data were translated into a result.

Finally, planning illustrations based on an observed effect serve a different purpose from evaluating trial results. In general, they explore participant requirements under assumptions; they do not measure observed power or compensate for sparse outcome information. Keeping those distinctions clear helps prevent a small, exploratory comparison from being interpreted as a definitive estimate.

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 small enrollment is a central limitation: the registry lists 10 participants overall and 5 in each group. The resulting primary outcome counts are sparse, so they offer limited precision and are sensitive to the outcomes of individual participants. The registry does not report a comparative estimate or confidence interval to quantify that uncertainty.

Important design and analysis details are not reported in the registry record. These include the randomization sequence and allocation concealment, baseline characteristics, the statistical analysis plan, the sample-size justification, and the primary analysis population. The record also does not describe whether all participants completed follow-up or how missing 6-month progression status was handled.

The endpoint description identifies freedom from disease progression at 6 months, but specific progression criteria, assessment procedures, and follow-up details are not reported in the registry record. This limits assessment of how consistently and completely the endpoint was measured. The study was unmasked, and the record does not report whether outcome assessment was conducted independently of treatment assignment.

Results for the listed secondary outcomes—response rate and grade 3 and grade 4 toxicity profiles—are not reported in the registry record. The record does not describe multiplicity procedures. Safety counts and listed serious adverse event terms provide limited descriptive information; details about causes of death, treatment attribution, and event timing are not reported in the registry record.

The study is identified as phase II, but the registry does not report its intended decision criteria or how the results were meant to guide subsequent research. These reporting limitations restrict what can be concluded from the record, independently of the observed counts.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Gemcitabine/ Trastuzumab and Gemcitabine/ Cisplatin/ Trastuzumab in Patients With Metastatic Breast Cancer — NCT00201760.
• Registry record last updated 2017-12-27; status last verified 2017-11.
• Results first posted 2017-11-09.
• 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

NCT00201760 is a completed randomized phase II parallel-group study with no masking. It enrolled 10 participants with metastatic breast cancer. Arm 1 received gemcitabine, cisplatin, and trastuzumab; Arm 2 received gemcitabine and trastuzumab. The registry lists 5 participants in each group.

The primary outcome was the number of participants free of disease progression at 6 months. The posted counts are 1 for Arm 1 and 0 for Arm 2. The registry record does not report a comparative statistical analysis, confidence interval, or primary-outcome test. Response rate and grade 3 and grade 4 toxicity profiles are listed as secondary outcomes, but their results are not reported in the registry record.

The record lists serious adverse events affecting 1 participant in Arm 1 and 0 in Arm 2, other adverse events affecting 5 participants in each group, and deaths of 1 and 0, respectively. These small descriptive counts do not establish comparative efficacy or safety. Details about the statistical plan, analysis population, and missing-data handling are not reported in the registry record.