A Study to Test the Benefit of a New Anti-cancer Treatment in Patients With Unresectable Advanced Melanoma: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for A Study to Test the Benefit of a New Anti-cancer Treatment in Patients With Unresectable Advanced Melanoma (NCT00942162), a non-randomized phase 2 study. The primary outcome is One-year Overall Survival Rate (OSR) Estimated by Complete Case Method.

2. Clinical Question

3. Trial Design

This was a phase 2, single-group, non-randomized study sponsored by GlaxoSmithKline. The registry record lists enrollment of 125 and identifies melanoma as the condition. The study started on 2009-08-14, reached primary completion on 2012-06-27, and has completed status. The official title describes GSK2132231A as first-line treatment for patients with unresectable metastatic melanoma.

Gene-signature status defined the groups: GS+ for patients with the pre-specified signature, GS- for patients without it, and GS-unknown when status was unknown. The record says the signature was assessed at screening and was considered potentially predictive. This grouping was not random allocation. Differences between groups could therefore reflect differences associated with signature status or other characteristics, as well as any differences in treatment exposure; the record does not establish that the groups were comparable.

The intervention is identified as a biological product. The GS+ description says patients received intramuscular MAGE-A3 ASCI in cycles, up to 24 doses in 4 cycles. The descriptions for the other signature groups say treatment was planned. These entries describe the intended treatment schedule, but do not give individual exposure or adherence results.

The primary endpoint was the one-year overall survival rate for the GS+ population, estimated by the complete-case method. Secondary outcomes included progression-free survival, overall survival, time to treatment failure, best overall response, duration of response, and duration of stable disease or time-to-progression, with several analyses specified by gene signature. There are 29 outcome measures listed, while the registry record reports no analyses. Numerical results for the primary endpoint 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: During the screening the following steps occurred: check for inclusion/ exclusion criteria, contraindications/ precautions, medical history of the patients and signing informed consent forms. While 125 subjects were enrolled, only 123 started the study, as 2 subjects did not receive treatment and were excluded.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: The analysis was performed on the Total Treated Population (TTP), which included all patients who received at least one dose of study treatment, but did not include patients who dropped out from the study (i.e. patients alive at the last evaluation visit and followed for less than 1 year at first database freeze).

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 One-year Overall Survival Rate (OSR) Estimated by Complete Case Method, measured over Month 0 - Month 12.

The primary endpoint is the one-year overall survival rate, described as the percentage of participants alive at the specified time point. The endpoint timeframe is Month 0 - Month 12, and the record says the rate was to be estimated by the complete-case method in the GS+ population. Overall survival is a time-to-event outcome: it concerns time until death, with participants who have not died by the relevant assessment treated as censored according to the analysis rules. The detailed censoring rules are not reported in the registry record.

A fixed-time survival rate expresses survival at a chosen horizon, while a confidence interval communicates uncertainty around that estimate. The record identifies a 95% confidence interval as the intended measure of precision. It sets a benchmark of 50% and a target of 71%, describing the latter as corresponding to a median overall survival of 24 months under an exponential distribution assumption. These are benchmark and target statements, not observed results. The registry record does not report the estimated one-year rate or its confidence interval, so precision and alignment with the target cannot be evaluated from the posted information.

Overall survival is used because it captures an outcome over time without relying on a judgment that a tumor has responded. It still requires clear definitions for the analysis population, follow-up, censoring, and handling of missing status. Those details matter when the analysis uses complete cases, particularly if follow-up differs across participants.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

What does a one-year survival rate represent?

Overall survival follows time from a defined starting point until death. A one-year overall survival rate is the estimated proportion alive at the one-year horizon. It condenses follow-up into a clinically interpretable time point, but does not show the full pattern of survival over time. Two studies can have similar rates at a chosen horizon while differing in when events occurred or in follow-up beyond that horizon.

Not every participant necessarily has a recorded death or a full year of observation. Survival methods can retain information from participants whose follow-up ends before death by censoring them at their last known status, provided the analysis assumptions and rules are appropriate. The registry identifies the complete-case method, but does not fully report the censoring rules or how incomplete observation was handled. The population description is truncated after mentioning patients alive at the last evaluation visit and followed for less than 1 year, so the intended handling of those cases is not fully clear from the record.

What does a confidence interval add?

A confidence interval describes the statistical uncertainty around an estimated quantity. A narrower interval indicates greater precision under the method used; a wider interval indicates more uncertainty. A 95% confidence interval is the stated uncertainty measure for this endpoint, but its limits are not reported in the registry record. Without both the estimate and its interval, readers cannot assess whether the data are compatible with a range of plausible one-year survival rates or how precisely the benchmark question was answered.

A confidence interval is not a guarantee that the true value lies within its particular limits, nor does it account for every source of uncertainty. It does not correct for selection bias, incomplete follow-up, measurement differences, or an unsuitable statistical model. Interpretation therefore depends both on the numerical interval and on the quality of the analysis and its assumptions.

How should the benchmark and target be read?

The endpoint description gives 50% as the stated maximum one-year overall survival rate for currently available treatment in the MAGE-A3-positive population, and 71% as the target for patients with the predictive gene signature. These values frame the intended comparison; they are not results from a concurrent control group. The target is linked in the record to median overall survival of 24 months when an exponential distribution is assumed. In general, an exponential model represents a constant event rate over time. If that assumption does not fit the data, the connection between a fixed-time survival rate and a median may not describe the observed survival pattern well.

What can be learned from the gene-signature groups?

Gene-signature status was assessed at screening, and the record classifies patients as GS+, GS-, or GS-unknown. These categories can support descriptive comparisons of outcomes by signature. Because allocation was non-randomized, differences among the groups are not equivalent to randomized treatment effects. Signature status may be associated with other patient or disease characteristics; the record does not report an adjusted analysis that would address such differences. The number of analyses is reported as zero, so no numerical subgroup analysis is available in the registry record.

What is over-dispersion, and does it apply?

Over-dispersion is a general statistical issue that arises when the variability in data is greater than a model assumes. It can make standard errors too small and confidence intervals too narrow if ignored. It is especially relevant to some count or clustered data models. The primary endpoint is a survival proportion at a fixed time, and the record does not report an over-dispersion assessment or a model for the endpoint. It would be inappropriate to claim that over-dispersion was tested or affected this analysis.

What do the planning illustrations mean?

Sample-size planning calculations are design illustrations, not evidence about how much power the completed study actually had. The stated assumptions for the illustrations include a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation; the effect to detect is described as a fraction of the observed effect. The instructions for the calculations distinguish time-to-event event totals from participants per arm for other outcomes. These assumptions describe the planning illustrations, not the actual single-group, non-randomized allocation described for this trial. Numerical sample-size illustrations are not reported in the registry record, and they should not be called observed power.

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("GSK2132231A GS+ Group", "GSK2132231A GS- Group", "GSK2132231A GS-unknown Group")
n      <- c(65, 48, 2)
events <- c(54, 40, 2)
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  GSK2132231A GS+ Group  65  54  83.1  71.7  91.2  72.2  90.3  72.1  90.2
ARM  GSK2132231A GS- Group  48  40  83.3  69.8  92.5  70.4  91.3  70.3  91.2
ARM  GSK2132231A GS-unknown Group  2  2  100.0  15.8  100.0  34.2  100.0  29.2  99.2

11. Multiplicity, Missing Data and Analysis Populations

The registry lists 29 outcome measures and names several secondary outcomes, including progression-free survival, overall survival, time to treatment failure, response, and duration measures. It also describes results by gene-signature group. Considering many outcomes and subgroups can increase the chance that at least one finding appears notable by chance, particularly when many statistical tests are conducted. This is the general multiplicity problem.

The registry record reports no analyses and does not describe a multiplicity adjustment, a hierarchy for testing endpoints, or a prespecified approach for selecting results. Those details are not reported in the registry record. The count of outcome measures should not be read as the count of completed statistical tests; the record does not establish how many analyses were performed outside the registered entries.

The primary endpoint is described as using a complete-case method in the Total Treated Population. That population includes patients who received at least one dose and excludes patients who dropped out, according to the available description. The record's explanation of exclusions is truncated, so the exact rule and its application cannot be fully assessed. Excluding participants with incomplete follow-up may affect an estimate if the likelihood of missing data is related to survival or prognosis. This is a general concern, not evidence that bias occurred in this study.

The record does not report how missing survival status, loss to follow-up, or other incomplete outcome data were handled, nor does it provide sensitivity analyses. These omissions limit assessment of whether the complete-case estimate would be robust to alternative missing-data assumptions. The numerical primary estimate and confidence interval are also not reported in the registry record, leaving both the result and its precision unavailable for evaluation.

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: pulmonary embolism (1.6%), lymphoedema (0.8%), phlebitis (0.8%), hip fracture (0.8%), laceration (0.8%).

The registry safety summary lists an overall study group with 123 at risk for serious events and 19 affected, alongside 123 at risk for other events and 107 affected. It also lists 3 deaths. The serious-event terms reported most often are pulmonary embolism at 1.6%, and lymphoedema, phlebitis, hip fracture, laceration, and overdose at 0.8% each. These figures are descriptive summaries of the registry entries.

“At risk” is the denominator reported for the event group; it should not be confused with the number of people who experienced an event. The record does not state in this summary whether event counts represent people with at least one event or total event episodes, nor does it provide timing, duration, exposure-adjusted rates, or an assessment of relatedness. The term list does not establish that each event was caused by the study treatment.

Because there is no randomized control group, the safety counts do not provide a direct comparative estimate of risk. The registry does not report enough detail in this summary to determine how complete event collection was or how the deaths relate temporally or causally to treatment. These figures should be read as reported counts and percentages, not as a causal conclusion.

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

The study was designed to examine the clinical activity of GSK2132231A in patients with MAGE-A3-positive unresectable metastatic melanoma, with particular attention to patients whose tumors had the potentially predictive gene signature. Its primary question concerned whether the one-year overall survival rate in the GS+ population would exceed a stated benchmark, with a higher target also specified.

The registry record does not report the observed one-year survival rate or its 95% confidence interval. As a result, the posted information cannot show whether the endpoint met the benchmark or target, or how precise any estimate was. The record also does not provide numerical results for the listed secondary outcomes. The absence of reported numerical results is not evidence that an endpoint had a particular value.

The design limits causal interpretation. Participants were not randomly assigned, and the signature categories were not concurrent randomized treatment arms. Comparisons with a historical benchmark or among signature groups may be affected by differences in patient characteristics, follow-up, or other factors. The record does not report an adjustment strategy that would resolve those concerns.

The listed safety figures document reported events in the overall study group, but they do not establish that the intervention caused those events or show how event risk compares with another treatment. Overall, the registry describes the research question, design, endpoint definition, and some safety summaries, but does not provide the outcome estimates needed to judge the primary result. It therefore supports an account of what was planned and registered, not a conclusion about treatment benefit.

14. Why This Trial Matters Statistically

This trial illustrates why the endpoint definition and the result must be read together. A one-year overall survival rate has a clear time horizon, and the registry states a confidence interval was intended to communicate precision. But without the estimate and interval, the key inferential information is unavailable. A target alone cannot indicate whether the observed data reached it.

It also illustrates the difference between a historical benchmark and a randomized comparator. The stated 50% benchmark provides context for the primary question, but it is not a control group enrolled and followed alongside the study participants. Non-randomized enrollment leaves potential differences between patients that can complicate causal interpretation. Separating descriptive association from evidence of a treatment effect is central to reading single-group research.

The gene-signature grouping raises an additional statistical question. The study sought to focus on a potentially predictive signature, but classification into GS+, GS-, and GS-unknown groups does not itself demonstrate that the signature predicts a different treatment effect. Such a claim would require suitable comparative evidence and an analysis addressing the relevant interaction; those results are not reported in the registry record.

Finally, the record lists multiple outcomes and provides a limited safety summary, while reporting no analyses. This makes completeness and multiplicity important parts of interpretation. Registry entries can clarify what investigators intended to assess, but registered aims, numerical results, and causal conclusions are distinct kinds of evidence. Keeping those distinctions explicit prevents a target or subgroup label from being mistaken for a demonstrated result.

15. Limitations

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

The primary limitation for interpreting efficacy is that the registry record does not report the one-year overall survival estimate or its 95% confidence interval. Without those values, the primary question cannot be assessed from the posted results. The record also reports no analyses, despite listing secondary outcomes and 29 outcome measures. Numerical results for those outcomes are not reported in the registry record.

The design is non-randomized and single-group, with no concurrent control arm. The gene-signature categories are subgroups, not randomized comparisons. The historical benchmark does not remove the possibility that differences in patient characteristics, care, or follow-up could influence comparisons. The record does not report adjusted analyses or enough detail to assess those potential sources of bias.

The primary endpoint description specifies a complete-case method, but the population explanation is truncated after describing exclusions for dropout and patients alive at the last evaluation with less than 1 year of follow-up. The exact handling of incomplete follow-up is therefore unclear. The registry does not report sensitivity analyses or detailed censoring rules. These gaps make it difficult to assess the effect of missing information on the endpoint.

The endpoint target's relationship to median overall survival relies on an exponential distribution assumption. The record does not report diagnostic checks or alternative analyses to assess that assumption. The safety summary gives event counts and selected terms, but does not provide detailed timing, exposure-adjusted rates, or causal attribution. These limitations are specific to the information and design described in the registry record; they do not establish that an unreported analysis or result had a particular outcome.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: A Study to Test the Benefit of a New Anti-cancer Treatment in Patients With Unresectable Advanced Melanoma — NCT00942162.
• Registry record last updated 2020-12-08; status last verified 2020-12.
• Results first posted 2018-09-07.
• 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

NCT00942162 is a completed phase 2, non-randomized, single-group study sponsored by GlaxoSmithKline. It enrolled 125 participants with melanoma and evaluated GSK2132231A, a MAGE-A3 antigen-specific immunotherapeutic, in unresectable metastatic disease. The study began on 2009-08-14 and reached primary completion on 2012-06-27.

The primary endpoint was the one-year overall survival rate in the GS+ population, estimated by a complete-case method over Month 0 - Month 12, with a 95% confidence interval. The endpoint description states a 50% benchmark and a 71% target. The observed estimate and interval are not reported in the registry record. Gene-signature groups were GS+, GS-, and GS-unknown; they were not randomized arms.

The record lists secondary survival, response, and duration outcomes, 29 outcome measures, and no analyses. Its safety summary reports 19 with serious events among 123 at risk, 107 with other events among 123 at risk, and 3 deaths. The available entries describe the study and its registered question, but do not provide the numerical efficacy results needed to assess the primary endpoint.