Dabrafenib and Trametinib With Radiosurgery in Melanoma Brain Mets: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Dabrafenib and Trametinib With Radiosurgery in Melanoma Brain Mets (NCT01721603), a na phase 2 study. The primary outcome is Patients Reaching 6 Month Distant Brain Metastasis-free Survival (DBMFS).

2. Clinical Question

The primary outcome is defined as the count of participants reaching 6 Month Distant Brain Metastasis-free Survival (DBMFS). Its stated timeframe is up to 6 months after surgery. The registry describes the study as a prospective phase 2 trial, but the record does not report a result that answers the comparison posed in the endpoint description.

3. Trial Design

The registry describes a phase 2 prospective trial for BRAFV600E melanoma brain metastases. It records a single-group model, allocation as not applicable, and no masking. The listed arm combines dabrafenib, trametinib and gamma knife radiosurgery. The primary endpoint description refers to stereotactic radiosurgery and a comparison with historical controls treated with radiosurgery alone; that proposed comparison is not a randomized, concurrent control comparison.

Enrollment is recorded as 2. The study began in 2013-04, had a primary completion date of 2016-01, and is listed as terminated. The reason for termination is not reported in the registry record. The dates and termination status describe the record, but do not explain how recruitment proceeded or why the trial stopped.

The study title and description frame the question around treatment of melanoma brain metastases. The endpoint description specifies patients for whom stereotactic radiosurgery is standard care, with up to 4 brain lesions and no lesion > 3 cm. The registry does not give further eligibility details, such as other clinical characteristics or the process used to determine eligibility.

A single-group study can describe outcomes among participants receiving its listed regimen, but it does not by itself provide a concurrent randomized estimate of how outcomes would differ under another treatment. Historical controls are mentioned as the intended reference for the primary question; the record does not report their data or a completed comparison. The arm description is also not a detailed treatment schedule. Dose, timing and treatment sequencing 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.

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 Patients Reaching 6 Month Distant Brain Metastasis-free Survival (DBMFS), measured over Up to 6 months after surgery.

The primary endpoint is the count of participants reaching 6 Month Distant Brain Metastasis-free Survival (DBMFS), with a timeframe of up to 6 months after surgery. In general, a metastasis-free endpoint is intended to describe whether distant brain metastases have occurred by the stated time; the registry frames this endpoint as a 6-month rate and a participant count. The word survival in the endpoint name should not be read as a reported survival curve or time-to-event estimate in the absence of such results.

The endpoint description gives the clinical rationale: compare the 6-month DBMFS rate for the combined regimen with similar historical controls treated with radiosurgery alone. A rate at a fixed time can be useful when the clinical question concerns the proportion of participants who have reached a specified status by a defined follow-up point. The record's primary measure, however, is stated as a count of participants, and it does not report the endpoint count, rate, uncertainty interval, or comparison result.

The reference to time after surgery is part of the stated timeframe. How surgery relates to the listed regimen and to the follow-up clock is not explained in the registry record. Nor does the record describe how distant brain metastases were assessed, how deaths or other events were handled in defining DBMFS, or how participants without follow-up through the target time were classified. Those details matter for interpreting a fixed-time endpoint and are not available in this record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry identifies a participant count as the primary measure: the number reaching 6 Month Distant Brain Metastasis-free Survival. This is a binary-outcome framing at a specified follow-up point. In general, each participant is classified according to whether the endpoint is reached, and the count describes how many meet that classification. A count alone is not a rate unless its denominator is also specified. For a meaningful rate, the population eligible for assessment and the handling of participants without an ascertainable outcome need to be clear. Those analysis details are not reported in the registry record.

What does a single-group design estimate?

A single-group study can describe outcomes among participants who receive the regimen under study. It does not create a randomized concurrent comparison, because participants are not assigned across treatment groups in the listed design. The primary endpoint description nevertheless sets out a comparison with similar historical controls treated with radiosurgery alone. In general, a historical comparison relies on information collected outside the trial group. Differences between the trial participants and the historical group, or in how outcomes were measured, can affect the comparison. The record does not report the historical-control data, selection criteria, or analysis used to make that comparison.

Allocation is listed as not applicable, and masking is listed as none. These entries are consistent with the stated single-group design; they do not describe a randomized allocation process. Lack of masking can matter when outcome assessment involves judgment or when awareness of treatment could affect reporting or follow-up. The registry does not say whether outcome assessment was blinded, how assessments were standardized, or whether independent review was used.

How should a fixed-time endpoint be read?

A fixed-time endpoint asks about status by a defined follow-up point, rather than reporting only an event count over all observed follow-up. The registry states a timeframe of up to 6 months after surgery. In general, interpretation depends on how the event is defined, how the time origin is set, how follow-up is conducted, and what happens analytically when a participant's status cannot be determined. The record does not report these rules. It also does not state whether participants were followed for the same duration or how events occurring before the target time were treated in the analysis.

Confidence intervals are a general way to express uncertainty around an estimate. They help readers assess how much precision the data support, rather than presenting an estimate as exact. The registry does not report a primary endpoint estimate or an uncertainty interval, so precision cannot be evaluated from this record. A p-value, if reported, would address compatibility with a specified statistical model and hypothesis; it would not by itself describe the size or clinical importance of an effect. No primary analysis or p-value is reported.

What do the planning assumptions mean?

The registry describes planning illustrations based on an observed effect, with a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. The stated effect to detect is a fraction of the observed effect. These are assumptions for hypothetical planning, not features that establish what happened in this single-group trial. The illustration description also distinguishes time-to-event calculations, which use a total number of events, from other calculations, which express participants per arm. The numerical planning estimates and the observed effect used as their basis are not reported in the registry record.

In general, a sample-size calculation asks what amount of information a future study might need to detect an effect under chosen assumptions. Its result depends on the assumed effect, variability or event frequency, design, significance threshold and target power. Changing those assumptions can change the planning estimate. Such an estimate is not the number of participants observed in the present trial, and it is not observed power. A planning exercise based on an observed effect can also be unstable when the source estimate is imprecise. The record does not give enough information to assess the assumptions beyond those stated or to reproduce the illustration.

For binary counts, methods often rely on assumptions about the event probability and the sampling process. In general, uncertainty can be substantial when the available number of observations is small, and an estimate can be sensitive to each observed outcome. The registry reports enrollment of 2 but gives no primary endpoint outcome count, so it is not possible to derive an endpoint estimate or assess its uncertainty. No new calculation is warranted from the enrollment figure alone.

What is not available for statistical review?

The registry lists no analyses. It does not report the statistical model, estimator, hypothesis test, confidence interval procedure, covariate adjustment, missing-data approach, analysis population, or endpoint adjudication method. This absence means the statistical analysis cannot be reconstructed from the record; it does not establish what analyses may or may not have been conducted outside the record. The distinction is important: design descriptions and planning assumptions do not substitute for posted outcome results or a specified analysis.

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 + Trametinib + Gamma Knife Radiosurgery")
n      <- c(2)
events <- c(1)
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 + Trametinib + Gamma Knife Radiosurgery  2  1  50.0  1.3  98.7  9.5  90.5  9.4  90.6

11. Multiplicity, Missing Data and Analysis Populations

The registry lists 8 outcome measures and names secondary outcomes including local control at 6 months, best overall response, freedom from new brain metastases, time to progression, systemic overall response, progression-free survival and overall survival. When a study evaluates multiple outcomes, general statistical practice considers multiplicity: repeated tests can increase the chance of a nominally positive result arising by chance if each is interpreted independently. Possible approaches include identifying a primary outcome in advance, defining a testing sequence, or adjusting inference. The registry record does not report a multiplicity strategy, and the listed outcomes alone do not establish whether or how any adjustment was planned.

The record identifies the primary endpoint as 6-month DBMFS, but does not report a primary analysis or any analyses. It does not describe an analysis population, such as whether all enrolled participants or only participants with specified assessments were included. It also does not state how missing endpoint assessments, incomplete follow-up, or participants whose status could not be determined were handled. These details are important for a fixed-time endpoint because classification depends on knowing the participant's status at the relevant time.

General missing-data methods rely on assumptions about why information is absent and how that absence relates to outcomes. Different assumptions can lead to different estimates, so transparent reporting is needed to interpret an analysis. No missing-data method or sensitivity analysis is reported in the registry record. The absence of these details prevents an assessment of how incomplete outcome information might affect the findings; it does not show whether missing information occurred.

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 non-serious adverse event terms

The safety figures are reported for a group labelled Dabrafenib With Gamma Knife Radiosurgery. The registry lists 2 participants at risk for serious adverse events and 0 affected. For other adverse events, it lists 2 at risk and 2 affected. Deaths are reported as 0. These are counts, not estimates of comparative risk, and the record does not give a concurrent control group for safety comparison.

The registry's listed treatment arm includes dabrafenib, trametinib and gamma knife radiosurgery, while the safety-group label names dabrafenib and gamma knife radiosurgery. The record does not explain this difference. It also does not give event descriptions for the other adverse events, their severity, timing, duration, or whether multiple events could have occurred in a participant. The serious adverse-event terms list is empty. An empty list does not provide further detail about events beyond the reported count.

These figures should be read as the safety information recorded for this group, not as a complete characterization of tolerability or a comparison between regimens. The small reported counts and absence of event-level detail limit what can be concluded. They do not answer the primary DBMFS question.

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

The registry record establishes that this phase 2 trial was designed as a prospective, single-group study of dabrafenib, trametinib and stereotactic radiosurgery in BRAFV600E melanoma brain metastases. It identifies a primary question about 6-month distant brain metastasis-free survival and describes historical controls treated with radiosurgery alone as the intended reference. It records enrollment of 2 and a terminated status. These registry entries describe the trial design and record status; they are not evidence of a treatment effect.

The record does not report the primary endpoint count, rate, estimate, or comparison. It therefore cannot show whether the stated endpoint was reached by participants, how the trial's outcome compared with historical controls, or what uncertainty surrounds any difference. The record also does not provide results for the named secondary outcomes. Neither the list of outcomes nor the trial's stated purpose should be interpreted as an observed result.

The safety counts offer limited descriptive information: 0 of 2 at risk had a serious adverse event reported, 2 of 2 at risk had other adverse events, and deaths were 0. With no event descriptions for the other adverse events and no concurrent control arm, these figures cannot establish comparative safety. The mismatch between the safety-group label and the listed treatment arm also calls for care when attributing the counts to the full regimen.

In general, a result from a small single-group study would need to be interpreted in light of uncertainty, follow-up, outcome assessment and the choice of historical reference. Those elements are not sufficiently to support a comparative conclusion. The most defensible reading is that the registry describes the question and design but does not post the outcome analysis needed to answer that question. The record does not establish benefit, lack of benefit, or a causal effect.

14. Why This Trial Matters Statistically

This trial raises a useful statistical distinction between a clinical question and the evidence needed to answer it. The primary endpoint description asks whether a combined regimen improves a 6-month outcome relative to historical controls. The design, however, is recorded as single-group, with no concurrent randomized comparator. A proposed historical reference and an observed controlled comparison are not the same thing: the latter requires comparator data and a transparent method for making the groups comparable.

The record also illustrates why outcome definitions and analysis details matter. A fixed-time DBMFS endpoint depends on how the event and time origin are defined and how follow-up status is established. The registry names the endpoint and timeframe, but does not report the primary result, missing-data rules, analysis population, or uncertainty estimate. Without these, readers cannot judge the magnitude or precision of an effect, even if the clinical question is clear.

The listed secondary outcomes widen the range of questions the trial intended to address. When multiple outcomes are considered, readers need to know which analyses were prespecified and how multiplicity was handled. The registry lists 8 outcome measures but does not report analyses or a multiplicity plan. This leaves the inferential status of any potential outcome comparison unclear.

Finally, the safety counts emphasize the difference between a count and a complete safety profile. Event totals without descriptions, timing or severity provide limited context, and a single-group record cannot establish comparative safety. The trial is statistically informative as an example of how design, outcome reporting and analysis transparency shape what can be concluded from a registry record, even when no efficacy analysis is posted.

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 registry record has substantial reporting gaps for assessing the trial's primary question. It does not report the primary endpoint result, a comparison with historical controls, an uncertainty interval, or a statistical test. Although the endpoint description specifies a timeframe of up to 6 months after surgery, the record does not explain the relationship between surgery and the listed regimen or how the follow-up clock was applied.

The historical controls are described as similar patients treated with radiosurgery alone, but their source, selection, characteristics, outcome data and follow-up are not reported. Without these details, comparability cannot be assessed. The single-group model and lack of a concurrent control also leave the proposed comparison vulnerable to differences between trial participants and historical patients. The allocation entry is not applicable, and no masking is listed.

Enrollment is recorded as 2, and the study status is terminated. The reason for termination, recruitment experience, and any effects of termination on follow-up or analysis are not reported in the registry record. Eligibility details beyond the primary description are also absent. Dose, treatment schedule, sequencing, endpoint assessment procedures and adjudication are not specified.

The registry lists 8 outcome measures but reports no analyses. It does not state an analysis population, missing-data strategy, multiplicity approach, or methods for estimating uncertainty. The safety information is limited to group-level counts and does not describe the other adverse events. The safety-group label also differs from the listed combination-treatment arm, with no explanation recorded. These limitations restrict interpretation of efficacy and safety; they do not establish what additional information may exist outside the registry record.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Dabrafenib and Trametinib With Radiosurgery in Melanoma Brain Mets — NCT01721603.
• Registry record last updated 2018-01-23; status last verified 2017-12.
• Results first posted 2018-01-23.
• 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 record describes a prospective phase 2 trial for BRAFV600E melanoma brain metastases. Its listed arm combines dabrafenib, trametinib and gamma knife radiosurgery. The design is single group, with allocation not applicable and no masking. Enrollment is 2; the study began in 2013-04, had primary completion in 2016-01, and is listed as terminated.

The primary endpoint is the count of participants reaching 6 Month Distant Brain Metastasis-free Survival, with a timeframe of up to 6 months after surgery. The endpoint description proposes comparison with similar historical controls treated with radiosurgery alone. The registry record does not report the primary endpoint result, a statistical analysis, or a comparison result. It lists 8 outcome measures and no analyses.

For the safety group labelled Dabrafenib With Gamma Knife Radiosurgery, the record reports 0 serious adverse events among 2 at risk, other adverse events in 2 of 2 at risk, and 0 deaths. Further event details and the reason for termination are not reported in the registry record.