Cetuximab in Combination With S-1 and Cisplatin in Gastric Cancer: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Cetuximab in Combination With S-1 and Cisplatin in Gastric Cancer (NCT01388790), a na phase 2 study. The primary outcome is Best Overall Response (BOR) Rate - Independent Review Committee (IRC) Assessments.

2. Clinical Question

Statistically, the central question is descriptive: what proportion of the defined population met the response criteria during follow-up? Because there is no comparator arm, the trial cannot estimate a randomized treatment contrast. Any observed response proportion would describe outcomes among participants treated with the combination, not establish how those outcomes compare with outcomes under another treatment. The registry record identifies an IRC assessment, but does not report the response count, percentage, or confidence interval. Consequently, the magnitude and precision of the primary response estimate cannot be evaluated from the reported results.

3. Trial Design

This was a completed, open-label, single-arm, multicenter phase II trial. The registry lists an enrollment of 40 and describes treatment of at least 40 participants. Allocation is listed as not applicable, consistent with the single-group design. Every eligible participant was assigned the combination of cetuximab, S-1, and cisplatin; there was no randomized control arm.

The treatment setting was first-line therapy for advanced gastric adenocarcinoma, including adenocarcinoma of the gastroesophageal junction. The brief description specifies that participants had not previously received systemic chemotherapy for this setting. The primary endpoint population included participants who received at least one dose of study treatment. The registry record does not provide further details about eligibility criteria, baseline characteristics, treatment dosing, or treatment duration; those details are not reported in the registry record.

The primary endpoint was best overall response rate assessed by an Independent Review Committee. Evaluations were performed every 6 weeks until disease progression. The stated reporting period ran from the day the first participant was treated, identified as July 2011, through the cutoff date of 14 August 2012. The registry record lists median progression-free survival assessed by the IRC as a secondary outcome.

The record gives a start date of 2011-06, primary completion of 2012-08, and status of completed. It does not report a statistical analysis plan, a sample-size justification, or interim analyses. Thus the design can be described from its structure and stated endpoint, but the rationale for the enrollment target and the planned inferential procedures are not 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.

Before assignment: Enrolled: 41 screened for eligibility; 1 excluded (non-fulfillment of inclusion or exclusion criteria) and 40 participants included in the study.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: ITT population included all participants who received at least one dose of study treatment.

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: Intent-to-treat (ITT) population included all participants who received at least one dose of study treatment.

6. Primary Endpoint

The registry lists the primary outcome as Best Overall Response (BOR) Rate - Independent Review Committee (IRC) Assessments, measured over Evaluations were performed every 6 weeks until disease progression, reported between day of first participant treated, that is July 2011, until cut-off date, (14 August 2012).

Best overall response rate is the percentage of participants whose best response during assessment was a confirmed complete response or partial response. The registry defines response using radiological assessments based on RECIST version 1.0, with the response assessed by an Independent Review Committee. Evaluations were scheduled every 6 weeks until disease progression.

As a binary endpoint, each participant is classified according to whether the qualifying response was achieved, and the rate expresses the proportion meeting that definition. In general, a response proportion offers a direct summary of how often a prespecified tumor-response category was observed in the assessed population. Requiring confirmation distinguishes the stated endpoint from a response recorded only once. Use of an independent review committee provides an assessment separate from the treating investigator, although the registry record does not describe the committee’s procedures or blinding.

The stated population for this endpoint is the ITT population, defined in the record as all participants who received at least one dose of study treatment. The record gives a 95% confidence interval as the dispersion measure, but does not report the response percentage or its interval. Therefore, the endpoint definition is available, while its observed estimate and precision are not reported in the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

In general, a single-arm trial estimates outcomes in one treated group. For a binary endpoint such as best overall response, the basic descriptive quantity is the proportion of participants who meet the response definition. That proportion is interpreted alongside its denominator and an uncertainty interval. The registry record defines the response endpoint and names a 95% confidence interval, but does not report the response estimate or interval limits.

What does a confidence interval describe?

In general, a confidence interval represents uncertainty arising from sampling variation under the method used to calculate it. It gives a range of values compatible with the observed data and stated procedure; it is not a guarantee that the true value lies within that range. Its width depends on features including the amount of information and the variability of the outcome. Because the response count, response percentage, and interval endpoints are absent from the registry record, the precision of this trial’s primary estimate cannot be assessed.

Why does the single-group structure matter?

In general, random allocation to a comparator helps support a causal comparison by making treatment groups comparable in expectation. This trial has no separate comparator group, so it can describe outcomes in the treated group but cannot estimate a randomized contrast. A response proportion is not itself a comparison with an alternative treatment, and it does not separate treatment effects from the course of disease, participant selection, or other influences. The registry record does not state a historical benchmark or comparative threshold for interpreting the response rate.

What role does the endpoint definition play?

The primary endpoint combines confirmed complete response and partial response as best overall response under RECIST version 1.0. In general, an explicit endpoint definition reduces ambiguity about which observations count toward an outcome. The record states that an Independent Review Committee assessed the endpoint and that radiological evaluations occurred every 6 weeks until disease progression. It does not report additional rules for confirmation, handling of unevaluable assessments, or the committee’s operating procedures. Such details are not reported in the registry record.

What can the assessment schedule tell readers?

Repeated evaluations can identify responses over the stated observation period and allow the best overall response to be determined. The timing information describes when assessments were planned, not how many were completed or whether participants had equal opportunities for assessment. In general, follow-up and assessment completeness matter because missed evaluations can affect classification of a binary response endpoint. The registry record does not report assessment completion or missingness for this outcome.

How should planning calculations be read?

In general, sample-size calculations are planning illustrations, not evidence about what a completed trial observed. The registry record does not report the trial’s own sample-size justification or statistical plan. Any planning illustration based on an observed effect and assumptions such as a two-sided significance level of 0.05, equal allocation, and a normal approximation is distinct from observed power. Such assumptions do not transform a single-arm study into a randomized comparison, and a planning result should not be treated as a trial outcome. The stated planning description also says that an effect to detect may be expressed as a fraction of the observed effect; no primary observed response result is reported in the registry record for readers to assess alongside such planning assumptions.

What is not available for independent verification?

The record does not report the numerical primary result, analysis procedures, or a detailed statistical plan. It therefore does not permit independent checking of the response calculation, the confidence interval method, or any adjustments to the primary analysis. The registry lists two outcome measures and identifies median progression-free survival assessed by the IRC as a secondary outcome, but the numerical secondary result is not reported. These omissions limit reproducibility and make it inappropriate to reconstruct an effect estimate.

In general, interpretation should keep three elements separate: the endpoint’s clinical definition, the estimated outcome, and uncertainty around that estimate. The definition and assessment schedule are recorded; the estimate and interval are not. The trial design also sets a clear boundary on inference: a single treated group can yield descriptive outcomes, but does not provide a randomized treatment comparison. These are limits on what can be concluded from the registry record, rather than evidence that an unreported result had any particular value.

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("Cetuximab Plus Cisplatin Plus S-1")
n      <- c(40)
events <- c(16)
for (i in seq_along(n)) {
  ci <- binom.test(events[i], n[i])$conf.int          # Clopper-Pearson exact interval
  cr <- qbeta(c(0.025, 0.975), 1 + events[i], 1 + n[i] - events[i])   # Bayesian, uniform Beta(1,1) prior
  wi <- (function(x, n) { p <- x / n; z <- qnorm(0.975); d <- 1 + z^2 / n
    c((p + z^2 / (2 * n) - z * sqrt(p * (1 - p) / n + z^2 / (4 * n^2))) / d, (p + z^2 / (2 * n) + z * sqrt(p * (1 - p) / n + z^2 / (4 * n^2))) / d) })(events[i], n[i])
  cat(sprintf("ARM|%s|%d|%d|%.1f|%.1f|%.1f|%.1f|%.1f|%.1f|%.1f\n", arm[i], n[i], events[i], 100 * events[i] / n[i],
              100 * ci[1], 100 * ci[2], 100 * wi[1], 100 * wi[2], 100 * cr[1], 100 * cr[2]))
}

ARM  Cetuximab Plus Cisplatin Plus S-1  40  16  40.0  24.9  56.7  26.3  55.4  26.3  55.5

11. Multiplicity, Missing Data and Analysis Populations

The registry record lists two outcome measures and identifies best overall response rate assessed by the IRC as primary. Median progression-free survival assessed by the IRC is listed as a secondary outcome. The record does not give numerical results for these endpoints or explain how inference across outcomes was handled. A multiplicity adjustment, hierarchy, or other control of multiple statistical tests is not reported in the registry record.

Multiplicity matters in general when several outcomes or analyses are tested, because examining multiple results can increase the chance of a seemingly notable finding by chance. The record does not report the number of planned analyses, detailed hypotheses, or any procedure for accounting for multiple comparisons. No claim about such procedures can be made from the available information.

The primary endpoint population is defined as all participants who received at least one dose of study treatment. That definition is reported, but the record does not state how missing or unevaluable response assessments were handled, whether participants were excluded from the endpoint calculation, or how participants without a confirmed response were classified. Those missing-data and analysis details are not reported in the registry record. The endpoint denominator and response count are also not reported, so the primary response rate cannot be reconstructed.

In general, missing outcome data can affect both the estimated proportion and its precision, depending on why observations are missing and how the analysis treats them. Without information on assessment completeness and analysis rules, the extent or direction of any such effect cannot be assessed.

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: decreased appetite (15.0%), pyrexia (5.0%), acute myocardial infarction (2.5%), electrocardiogram t wave inversion (2.5%), soft tissue necrosis (2.5%).

The registry record lists one treatment group, with 40 participants at risk for serious adverse events and 15 affected. For other adverse events, it lists 40 at risk and 40 affected. These are event-category counts recorded for the study group, not a comparison between treatment groups. The record does not provide a control group against which to judge relative rates.

The listed serious adverse event terms and percentages are decreased appetite, 15.0%; pyrexia, 5.0%; acute myocardial infarction, 2.5%; electrocardiogram T wave inversion, 2.5%; soft tissue necrosis, 2.5%; and renal artery thrombosis, 2.5%. These entries identify reported terms and their listed percentages; they do not establish that the treatment caused each event. The registry record does not describe event-level timing, severity grading beyond the serious classification, or attribution procedures.

Deaths are not reported in the registry record. In general, adverse-event counts depend on the definitions, observation period, and reporting practices used. The figures describe the safety information recorded for this study group and should not be interpreted as comparative risk estimates.

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

The registry record allows readers to identify the question the study set out to address: the best overall response rate for a combination of cetuximab, S-1, and cisplatin in participants with advanced gastric adenocarcinoma, including gastroesophageal junction adenocarcinoma. It also specifies a confirmed response definition based on RECIST version 1.0 and assessment by an Independent Review Committee.

However, the primary response percentage and its 95% confidence interval are not reported in the registry record. The posted information therefore does not establish how often the defined response occurred or how precisely it was estimated. The secondary progression-free survival outcome is identified, but its result is also not reported in the registry record. The safety listing gives event counts and selected serious adverse event terms, but those data do not supply the missing efficacy estimate.

Even if a response result were available, the single-arm design would support a description of outcomes in the treated group rather than a randomized estimate of comparative effect. There was no separate control group, so this trial cannot answer how outcomes would differ under another treatment. Observational contrasts with other studies would not have the same protection against differences in participants and study conduct that randomization provides.

In general, a point estimate describes the observed outcome, while its confidence interval communicates uncertainty. Neither element can be evaluated for the primary endpoint from the result information in the registry record. The absence of the reported estimate should not be mistaken for a zero response or for evidence of no effect; it means the outcome value is not reported in the registry record.

The appropriate conclusion is therefore bounded: the trial’s design, population description, endpoint definition, assessment timing, and listed safety information are available, but the primary outcome result and its precision are not. No medical recommendation or conclusion about treatment effectiveness follows from these registry entries alone.

14. Why This Trial Matters Statistically

This trial is statistically notable for the distinction between a clearly specified endpoint and an unavailable numerical result. The record defines best overall response as confirmed complete or partial response, names the assessment criteria, identifies an independent review committee, and gives the evaluation schedule. These details explain what the primary outcome was intended to measure. Yet without the response count, percentage, and confidence interval, readers cannot judge the observed outcome or its precision.

The single-arm structure also illustrates why endpoint estimates and treatment comparisons are different questions. A response proportion can describe what was observed among participants receiving the regimen. It cannot, on its own, show how that outcome compares with a different treatment or what would have occurred in a control group. Recognizing this design boundary is central to interpreting phase II evidence without overstating causal conclusions.

The record also highlights the importance of transparent reporting beyond endpoint definitions. Information on missing assessments, analysis procedures, multiplicity, and sample-size justification would help readers assess how results were generated and how robust the interpretation might be. Those details are not reported in the registry record. Their absence does not establish that a particular method was or was not used; it limits what can be verified from the record.

Finally, safety counts and selected serious event terms provide descriptive context but do not create a comparative safety analysis. The statistical lesson is to distinguish what the registry documents from what would require additional results or study design features. In this case, the design and definitions are described, while the primary numerical outcome and several analytical details remain unreported.

15. Limitations

• The posted summary statistics are the only data these results rest on; patient-level data, full protocols and statistical analysis plans are not available.
• Recalculated results are simple, unadjusted calculations from posted summaries. They do not replace the sponsor's prespecified analysis.

The main trial-specific limitation in interpreting the registry record is that the numerical primary outcome is not reported. Although the endpoint definition and confidence-interval measure are stated, the response count, rate, interval limits, and endpoint denominator are absent. The response estimate and its precision therefore cannot be independently assessed.

The study was single-arm and open-label, with no randomized comparator. This limits interpretation to outcomes in the treated group and prevents a direct randomized comparison. The record does not describe a historical benchmark or a prespecified threshold against which the response rate was intended to be judged.

Some details needed to understand outcome ascertainment are also not reported in the registry record. These include the handling of missing or unevaluable response assessments, completeness of follow-up assessments, detailed analysis procedures, and the statistical plan. The record states that evaluations occurred every 6 weeks until disease progression, but does not report how many assessments were completed or whether any were missing.

The registry describes an enrollment of 40 and an ITT population defined by receipt of at least one dose, but does not give the number contributing to the primary endpoint analysis. The listed safety counts do not resolve that efficacy-analysis uncertainty. Nor does the record provide numerical results for the listed secondary progression-free survival outcome. These limits are specific to the information reported for this trial and restrict independent assessment of its outcomes.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Cetuximab in Combination With S-1 and Cisplatin in Gastric Cancer — NCT01388790.
• Registry record last updated 2013-11-20; status last verified 2013-09.
• Results first posted 2013-11-20.
• 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

NCT01388790 is a completed, open-label, single-arm, multicenter phase II trial of cetuximab, S-1, and cisplatin for advanced gastric adenocarcinoma, including adenocarcinoma of the gastroesophageal junction. The registry lists enrollment of 40 and describes first-line treatment for participants who had not previously received systemic chemotherapy for this setting.

The primary endpoint was IRC-assessed best overall response rate, defined as confirmed complete or partial response under RECIST version 1.0. Assessments were scheduled every 6 weeks until progression. Median progression-free survival assessed by the IRC is listed as a secondary outcome. The numerical primary and secondary outcome results are not reported in the registry record.

The record lists serious adverse events for the treatment group and selected serious event terms. It does not report a comparator, detailed statistical plan, sample-size justification, multiplicity procedure, or handling of missing response data.