Adjuvant Dabrafenib (GSK2118436) in Patients With Surgically Resected AJCC Stage IIIC Melanoma Characterized by a BRAFV600E/K Mutation: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Adjuvant Dabrafenib (GSK2118436) in Patients With Surgically Resected AJCC Stage IIIC Melanoma Characterized by a BRAFV600E/K Mutation (NCT01682213), a na phase 2 study. The primary outcome is Percentage of Participants With Relapse Free Survival.

2. Clinical Question

In plain terms, the study asked whether participants in this selected postoperative population remained free of recurrence or death during the stated follow-up period while receiving adjuvant dabrafenib. That is a description of the research question, not a conclusion about treatment effect. Without a reported endpoint estimate and without a concurrent comparator, the registry record does not establish how often relapse-free survival occurred or how that experience compares with another approach.

3. Trial Design

The registry describes a phase 2, single-group study sponsored by Memorial Sloan Kettering Cancer Center. Enrollment was 23. The listed intervention was dabrafenib, and the arm description identifies the study as a single-institution assessment of adjuvant treatment for participants with surgically resected AJCC stage IIIC melanoma characterized by a BRAFV600E/K mutation. The record lists the study as completed, with a start date of 2012-09 and primary completion in 2019-05.

Allocation is listed as not applicable, consistent with the single-group model; masking is listed as none. These design features mean the record does not describe random assignment or masking of participants, clinicians, or outcome assessors. The registry does not report a separate control arm. Consequently, the posted design supports description of outcomes in the enrolled group but does not provide a randomized between-group treatment contrast.

The primary outcome was the percentage of participants with relapse-free survival at 24 months. The registry defines the endpoint using time from surgical resection to first recurrence or death. It says recurrence was assessed by physical examination and radiographic evaluation and confirmed by biopsy and histologic evaluation. Overall survival and the number of participants with adverse events are listed as secondary outcomes.

The record does not report the numerical primary outcome result, numerical overall-survival results, or a detailed statistical analysis plan. It also does not report a sample-size justification or the rationale for choosing a single-group design. The completion status and dates describe the registry record; they do not by themselves indicate whether outcome data were complete or whether the planned analyses were performed.

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: 2 participants withdrew consent 1 week after signing consent

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 Percentage of Participants With Relapse Free Survival, measured over 24 months.

The primary endpoint is described as the percentage of participants with relapse-free survival at 24 months. The registry defines relapse-free survival as the time from surgical resection to the first recurrence or death. This definition combines recurrence and death as events for the endpoint. Recurrence was assessed through physical examination and radiographic evaluation, with biopsy and histologic evaluation used for confirmation.

As a general statistical concept, a relapse-free endpoint can summarize how long participants remain without a specified disease event. Combining recurrence and death can capture more than recurrence alone, but the endpoint’s meaning depends on its operational definition, follow-up, and handling of incomplete observations. The registry gives the definition and timeframe, but does not report enough information to determine how censoring, missing follow-up, or withdrawals were treated in the analysis.

The title frames the measure as a percentage at a stated follow-up point, while the definition describes time from surgery to an event. Those descriptions are related but do not supply the actual estimate, its uncertainty, or the analysis method. The numerical result for relapse-free survival is not reported in the registry record. The reason for selecting this endpoint, beyond its listing as the primary outcome, is also not reported in the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry classifies the primary outcome as a percentage of participants and gives its timeframe as 24 months. It also defines relapse-free survival using time from surgical resection to first recurrence or death. These descriptions identify what the outcome is intended to represent, but they do not reveal which statistical procedure was used to estimate it. The analysis method, estimate, and uncertainty interval are not reported in the registry record.

As a general statistical explanation, a percentage is a way to express the share of an analysis population meeting a stated condition. Interpreting such a percentage requires knowing the numerator, denominator, and rules for determining whether each participant met the condition. For an endpoint defined over follow-up, it is also important to know how incomplete observation is handled. The registry reports enrollment of 23 and notes 2 withdrawals in the primary-outcome population description, but it does not state the endpoint analysis denominator or the handling of those withdrawals. No primary-outcome percentage is reported.

The definition also has a time-to-event structure: the relevant event is the first recurrence or death after resection. In general, time-to-event methods can use the timing of events and account for participants whose event status is not observed throughout follow-up, provided the method and assumptions are appropriate. The registry record does not identify a time-to-event estimator, a censoring rule, or any assumptions used. It is therefore not possible to tell whether the posted endpoint was analyzed as a time-to-event outcome, as a fixed-time percentage, or through another approach.

As a general explanation, uncertainty intervals describe the range of estimates compatible with the observed data under a statistical method and its assumptions. They help distinguish a precise estimate from one that is highly uncertain. No interval for the primary outcome is reported, so its precision cannot be assessed. No p-value or test result for the primary endpoint is reported either. The absence of these quantities does not imply a particular result; it means that the registry record does not provide them.

The single-group design is central to interpretation. A study with one treatment group can report outcomes in that group, but it does not create a randomized comparison between treatments. Even if an outcome estimate were available, comparison with results from a different study would require careful consideration of differences in participants, follow-up, outcome definitions, and other design features. The registry record does not report a comparator group or a planned comparative analysis.

General statistical methods can also address over-dispersion when observed variation is greater than a model expects. That issue matters when a chosen model assumes less variability than the data contain, because standard errors and uncertainty estimates may then be too small. The registry record does not report a model for the primary outcome or identify over-dispersion as an issue, so it is not possible to say whether that concept applied to this analysis.

The record lists the study as phase 2 and gives enrollment of 23, but it does not report a sample-size justification or a statistical plan explaining the target enrollment. A planning calculation based on an observed effect, when presented as an illustration, is not the trial’s original design justification and is not observed power. The record does not include an observed primary effect from which such an illustration could be interpreted. The planning assumptions listed for hypothetical calculations include a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation; those are planning assumptions, not evidence that this single-group trial used a two-arm design or those methods for its primary analysis.

There is no reported primary analysis to compare against an independent recalculation. In general, a recalculation from summary data is unadjusted and can differ from a sponsor’s analysis if the latter uses different methods or analysis populations. When a discrepancy is identified, the sponsor’s own analysis takes precedence. No such primary-outcome comparison is available in the registry record, and no observed-power conclusion can be drawn.

The registry lists overall survival and the number of participants with adverse events as secondary outcomes. A statistical analysis of multiple outcomes may need to address the possibility of chance findings from repeated testing, depending on the planned inferential claims. The record does not report a multiplicity strategy, interim analyses, or a detailed statistical analysis plan. These omissions do not establish that such procedures were or were not undertaken outside 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("Dabrafenib")
n      <- c(21)
events <- c(6)
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  Dabrafenib  21  6  28.6  11.3  52.2  13.8  50.0  13.9  50.2

11. Multiplicity, Missing Data and Analysis Populations

The record identifies a primary outcome and lists overall survival and the number of participants with adverse events as secondary outcomes. It also reports 3 outcome measures, but does not provide a detailed analysis plan describing how those outcomes were tested or prioritized beyond the primary and secondary labels. The registry does not report a strategy for controlling multiplicity or explaining how multiple statistical tests would be interpreted.

As a general statistical issue, assessing several outcomes can increase the chance of at least one apparently notable result arising by chance when each is tested separately. Whether adjustment is appropriate depends on the inferential aims and planned analyses. The record does not say whether any adjustment was planned or used. It also does not report interim analyses, stopping rules, or other repeated looks at outcome data.

Missing-data handling is particularly relevant because the primary-outcome population note says that 2 participants withdrew consent 1 week after signing consent. The record does not explain whether they were excluded from the endpoint analysis, followed for outcomes, or included under a particular analysis-population definition. It does not report how missing endpoint status or incomplete follow-up was handled, or whether any sensitivity analyses were performed.

Terms such as intention-to-treat, per-protocol, and safety population refer to different analysis populations and can produce different summaries. The registry record does not identify which analysis populations were used for the primary or secondary outcomes. It also does not provide a statistical analysis plan or enough information to infer one. Therefore, the effect of withdrawals, missing observations, and multiplicity on the results cannot be evaluated from the registry record.

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 0% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: neoplasms ben/mal/unk (inccyst/polyp) other, spec (13.0%), fever (8.7%), anemia (4.3%), chills (4.3%), cough (4.3%).

The safety record lists a dabrafenib group with 23 participants at risk for serious adverse events and 5 affected by serious adverse events. For other adverse events, it lists 23 at risk and 23 affected. It also lists 8 deaths. These are distinct summaries: adverse-event counts do not by themselves establish that an event was caused by treatment, and the death listing does not state a causal relationship.

The listed serious-event terms and percentages are Neoplasms ben/mal/unk (inccyst/polyp) Other, spec at 13.0%, Fever at 8.7%, and Anemia, Chills, Cough, and Platelet count decreased at 4.3% each. These are term-level entries. The registry record does not explain whether the term percentages represent unique participants, event occurrences, or another counting convention, and it does not give further details about timing, severity grading, or attribution.

As a general safety-reading principle, the number of participants affected and the frequency of listed event terms answer different questions. A participant may experience more than one event, so term listings should not automatically be treated as mutually exclusive participant groups. The posted safety information describes events recorded in the study; it does not establish that dabrafenib caused them.

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

The record establishes that a phase 2, single-group study evaluated adjuvant dabrafenib in participants with surgically resected AJCC stage IIIC melanoma characterized by a BRAFV600E/K mutation. It specifies relapse-free survival at 24 months as the primary endpoint and defines recurrence or death as the first qualifying event. It also reports enrollment, study status, dates, and safety summaries.

The registry does not report the numerical primary endpoint result or its precision. It therefore does not show the observed relapse-free survival percentage, how many participants experienced recurrence or death, or how uncertain an estimate would be. A numerical conclusion about the primary outcome cannot be drawn from this record.

The single-group design also limits what any outcome estimate could establish. Without a concurrent control group, the study does not provide a direct comparison with another treatment or with no treatment. A description of outcomes among participants receiving dabrafenib would not, by itself, demonstrate that the intervention caused those outcomes. No claim that the treatment works or does not work follows from the information.

The safety entries provide counts of participants affected by adverse events and a list of serious-event terms, along with deaths. They do not establish causality, and the registry does not give enough detail to interpret the listed terms as unique people or event counts. The secondary outcome names are present, but their numerical results are not reported in the registry record.

The appropriate reading is therefore limited: the study design and endpoint are described, while the primary result, its uncertainty, analysis-population details, and key statistical methods remain unreported. The record is informative about what the investigators set out to assess, but it does not supply the data needed for a quantitative efficacy conclusion or a comparative treatment conclusion.

14. Why This Trial Matters Statistically

This trial is statistically informative as an example of how design determines the questions a study can answer. A single-group study can characterize outcomes in its enrolled participants, but without a control group it cannot provide a randomized estimate of the difference between dabrafenib and another strategy. That distinction remains important even when the population and endpoint are clearly specified.

The endpoint combines recurrence and death and is defined from the time of surgical resection. Its interpretation depends on how event timing, incomplete follow-up, and withdrawals are handled. The registry gives the endpoint definition and notes withdrawals in the primary-outcome population description, but does not report the analysis rules or the numerical result. This makes the record a useful illustration of why endpoint definitions alone are not enough for evaluating an estimate.

Precision is also essential. A result without an uncertainty measure can be difficult to distinguish from a result that is compatible with a wide range of underlying outcomes. Here, neither the primary estimate nor its uncertainty is reported. The registry lists enrollment of 23, but enrollment alone cannot substitute for the outcome data or an analysis.

Finally, the separation between efficacy and safety summaries matters. The adverse-event counts and terms describe safety observations, but do not establish causality or answer the primary relapse-free survival question. Reading these pieces separately helps avoid treating a study’s completion status, event listings, or design description as evidence of an unreported treatment effect.

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 principal limitation for statistical interpretation is that the numerical primary endpoint result is not reported in the registry record. The record gives a 24-month timeframe and defines relapse-free survival, but does not give an estimate, event count, confidence interval, or other measure of precision. The listed overall-survival and adverse-event outcomes also lack numerical outcome results in the record.

The study is single-group and has no reported concurrent comparator. This prevents a direct randomized comparison and limits causal interpretation of outcomes observed in the treated group. The registry lists enrollment of 23, but does not provide a sample-size justification or enough outcome data to assess how informative the study was for its primary question.

The record notes that 2 participants withdrew consent 1 week after signing consent. It does not clarify their inclusion in the endpoint analysis, how incomplete follow-up was handled, or which analysis population was used. The statistical methods, including any censoring rules, are not reported. The record also does not report a multiplicity strategy, interim analyses, or the detailed analysis plan.

The safety entries list affected-participant counts and serious-event terms, but the record does not explain the counting convention for the term percentages or provide event attribution. These limitations restrict interpretation of the safety summaries as well as the unreported efficacy endpoint. No additional protocol details or analysis decisions can be inferred from the registry information.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Adjuvant Dabrafenib (GSK2118436) in Patients With Surgically Resected AJCC Stage IIIC Melanoma Characterized by a BRAFV600E/K Mutation — NCT01682213.
• Registry record last updated 2020-05-26; status last verified 2019-05.
• Results first posted 2020-05-26.
• 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

NCT01682213 is a completed phase 2, single-group study sponsored by Memorial Sloan Kettering Cancer Center. It enrolled 23 participants with surgically resected AJCC stage IIIC melanoma characterized by a BRAFV600E/K mutation and evaluated adjuvant dabrafenib. The recorded start date is 2012-09, and primary completion is listed as 2019-05.

The primary outcome was the percentage of participants with relapse-free survival at 24 months, defined by time from resection to first recurrence or death. Overall survival and the number of participants with adverse events were listed as secondary outcomes. The registry does not report the numerical primary result or detailed statistical methods.

The record notes 2 consent withdrawals 1 week after signing consent. Safety data list 5 participants with serious adverse events among 23 at risk, 23 with other adverse events among 23 at risk, and 8 deaths. Those entries do not establish causality. The single-group design provides no direct randomized comparison.