Continuation Study of the Oral AKT Inhibitor GSK2110183: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Continuation Study of the Oral AKT Inhibitor GSK2110183 (NCT01531894), a na phase 2 study. The primary outcome is Number of Participants With at Least One Adverse Events (AEs).

2. Clinical Question

The central question is therefore descriptive: what adverse-event experience was recorded among participants continuing afuresertib in this study? The reported adverse-event figures include 11 participants with any adverse event, 2 with a serious adverse event, and 1 death. Gastritis and pneumonia are each listed among the leading serious adverse-event terms, with 9.1% reported for each.

These results need to be read in the context of eligibility. Participants were not starting treatment as an unselected group: they had previously received the drug in a parent study, and the rollover eligibility criteria required prior clinical benefit and an acceptable safety profile. The record also allowed participation after some combination studies involving an approved anti-cancer agent. It does not describe a randomized comparison or a separate efficacy endpoint in the posted results. The findings address the safety experience recorded during continuation, not the effect of treatment relative to another option.

3. Trial Design

This was a phase 2, multicenter, non-randomized, open-label continuation study of GSK2110183, also called afuresertib. Its purpose was to provide continued access to treatment for eligible participants who had previously participated in a GSK2110183 study sponsored by GlaxoSmithKline or another research organization working on its behalf. The registry classifies the design as single-group, with no masking and no randomized allocation.

Eligibility depended in part on experience in the parent study. Participants had to have received clinical benefit from continued treatment and have an acceptable safety profile with GSK2110183. Participants from combination studies with an approved anti-cancer agent could also be eligible. Those from combination studies involving two investigational compounds, one of which was GSK2110183, were not eligible. Cohorts were based on the duration and treatment received in the parent study. The registry does not provide further cohort-level results.

All patients in the listed arm received GSK2110183. There was no like-for-like control arm, so the study cannot support a randomized treatment comparison. The registry records enrollment of 11 and gives a study start date of 2012-02-08, primary completion date of 2018-06-20, and completed status. The primary adverse-event timeframe ran from consent until the final study visit, up to approx. 76 months.

Safety assessments included physical examinations, vital sign measurements, electrocardiograms, echocardiograms or multiple-gated acquisition scans, clinical laboratory assessments, and monitoring of adverse events. Disease assessments used local standard-of-care imaging practices and criteria appropriate to disease type and location. The record does not report the specific statistical plan, how cohort results were combined, or a protocol-based sample-size justification. The study design is therefore best understood as continued treatment access with safety monitoring, rather than a controlled efficacy trial.

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: There was no planned duration of treatment as this was a rollover study. The subjects could permanently discontinue the study treatment due to protocol deviation, adverse event, disease progression, withdrawal of consent, Investigator's discretion, lost to follow-up, termination of study or death.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: The 'all treated subjects' population consisted of all subjects that received at least one dose of afuresertib in this rollover 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.

Population: The 'all treated subjects' population consisted of all subjects that received at least one dose of afuresertib in this rollover study.

6. Primary Endpoint

The registry lists the primary outcome as Number of Participants With at Least One Adverse Events (AEs), measured over from the time of consent until the final study visit up to approx. 76 months.

The primary endpoint was the number of participants with at least one adverse event. The defined population included all treated participants, meaning those who received at least one dose of afuresertib in the rollover study. The timeframe extended from consent through the final study visit, up to approx. 76 months.

The endpoint description covers a broad set of safety outcomes: adverse events overall, drug-related adverse events, serious adverse events, adverse events that led to treatment discontinuation, and death. These outcomes are clinically and statistically distinct, even though the endpoint description groups them within the adverse-event assessment. A participant-level count records whether a participant experienced an event; it does not, by itself, describe how many events occurred, how long they lasted, or how severe each non-serious event was.

General: safety endpoints are used to characterize harms observed during treatment and follow-up. They can identify events that warrant closer examination, but a count alone does not establish that treatment caused an event. Attribution, event definitions, duration of exposure, and the context of a comparison group all matter when interpreting safety data.

The registry reports any adverse event for 11 participants and serious adverse events for 2. It also reports 1 death. The record does not provide a separate numerical result for drug-related adverse events or adverse events leading to treatment discontinuation. Nor does it report comparative estimates or confidence intervals for this endpoint. The reported counts therefore describe the observed safety experience, but do not quantify a treatment effect against a control.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

General: the registry reports participant counts for safety outcomes. A count describes how many participants were recorded with an event under the stated outcome definition. It is not the same as an event rate over person-time, because the record does not provide person-time calculations for these outcomes. It also does not indicate how many separate episodes a participant experienced.

What does a single-group design allow?

The study is classified as non-randomized and single-group. Participants received afuresertib, and there was no randomized control group against which to compare their outcomes. In a randomized comparison, treatment assignment helps create groups that can be compared under a defined analysis. Here, the results instead describe the experience of participants enrolled in the continuation study. A difference from an external population or from another study cannot be interpreted as a treatment effect without additional evidence and suitable methods.

The open-label design means the study was not masked. The registry does not report whether any particular safety assessment was independently reviewed or adjudicated. General: awareness of treatment can influence reporting or assessment of some outcomes, although serious events may also be defined and reviewed through specified procedures. The procedures used for this study beyond the safety assessments listed in the record are not reported in the registry record.

How should counts and percentages be read?

The adverse-event record gives 11 participants at risk for the serious and other event summaries. It reports 2 participants with serious adverse events, 11 with other adverse events, and 1 death. The listed serious terms gastritis and pneumonia each have a reported percentage of 9.1%. These figures should be read as registry summaries, not as independent observations or estimates of comparative risk. The record does not provide enough detail to determine whether participants could be represented in multiple event categories, how repeat events were handled, or whether term-level percentages used the same event definition as the overall counts.

General: a confidence interval expresses uncertainty around an estimate under a statistical model and analysis plan. It is useful because an observed count or percentage does not show how precisely the underlying quantity has been estimated. No confidence interval for the primary endpoint is reported in the registry record. A p-value would address compatibility with a specified statistical hypothesis under model assumptions, but no inferential result for the primary endpoint is reported either. With no control group, such a result would not by itself supply a treatment comparison.

What do the sample-size assumptions mean?

The registry includes a description of 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. Those assumptions describe an illustration, not the design of this single-group continuation study. The record does not report a trial-specific sample-size justification or a randomized two-arm design. Any sample-size illustration based on an observed effect is planning information, not observed power and not evidence that the study had a particular probability of detecting an effect.

General: power is a design property tied to a specified effect, variability, significance level, and analysis. It is not a measure of whether a result is true, and it should not be inferred from the observed outcome. Since the reported results do not give a trial-specific power calculation or a controlled treatment comparison, no conclusion about the study’s ability to detect a treatment difference follows from the adverse-event counts.

Why can variability matter?

General: some event-count outcomes vary more than a simple statistical model expects, a feature called over-dispersion. If over-dispersion is present, standard errors from a model that assumes less variability may be too small, making uncertainty appear narrower than it is. The registry record does not report a count model or a dispersion estimate, and the primary endpoint is a participant count rather than a reported modeled event rate. It would therefore be inappropriate to assert that over-dispersion was assessed or to apply a model that is not described.

The study also used local standard-of-care imaging and disease-appropriate criteria for disease assessment. No efficacy analysis is reported in the registry record. The methods and conclusions described by the posted results are consequently limited to the recorded safety summaries and the design information in the registry.

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("GSK2110183 (Afuresertib)")
n      <- c(11)
events <- c(11)
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  GSK2110183 (Afuresertib)  11  11  100.0  71.5  100.0  74.1  100.0  73.5  99.8

11. Multiplicity, Missing Data and Analysis Populations

The registry record does not report a statistical analysis plan, a hierarchy of hypotheses, or a multiplicity adjustment. It names one primary safety endpoint, but also describes several related safety categories, including drug-related adverse events, serious adverse events, events leading to treatment discontinuation, and death. The record does not state whether formal tests were planned for these outcomes or how any multiple testing would have been handled. No inferential analysis is reported, so the effects of multiplicity on statistical conclusions cannot be assessed.

Missing-data handling is not reported in the registry record. The record does not describe how participants with incomplete follow-up, missing assessments, or unavailable event information were handled. The primary endpoint population is defined as all treated participants, those who received at least one dose of afuresertib in the rollover study. This definition does not by itself explain how missing observations were treated or whether follow-up time differed among participants.

The registry reports enrollment of 11 and gives the all-treated population definition, but it does not provide a participant flow account or detailed analysis-population counts beyond the adverse-event summaries. The results should therefore be interpreted as the posted counts, without assuming that missing observations were absent or handled in a particular way. Details on imputation, censoring, sensitivity analyses, or missing-data assumptions are not reported in 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 5% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: gastritis (9.1%), pneumonia (9.1%).

The serious adverse-event summary reports 2 participants with a serious adverse event among the 11 listed as at risk. The same summary reports 11 participants with other adverse events and 1 death. These are registry counts; they are not a comparison with a control group and do not establish that afuresertib caused an event.

Gastritis and pneumonia are the leading serious adverse-event terms listed, with 9.1% reported for each. The record does not give event timing, duration, clinical course, or a separate causal assessment for these terms. A term appearing in a serious-event summary does not, on its own, indicate how many episodes occurred or whether the event was judged related to treatment.

The endpoint description includes drug-related adverse events, serious adverse events, events leading to treatment discontinuation, and death. However, the posted figures do not give separate numerical results for drug-related events or treatment discontinuations. The death count is reported, but the record does not state that the death was treatment-related. The findings are best read as a descriptive account of events recorded during follow-up, not as proof of causation or a comparative estimate of safety.

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

The result describes adverse events recorded during an open-label continuation study of afuresertib in participants who had previously taken part in a GSK2110183 study. The registry reports any adverse event for 11 participants, serious adverse events for 2, and 1 death. It also lists gastritis and pneumonia among the leading serious adverse-event terms, each reported at 9.1%. These observations provide a safety description for the study population and follow-up period stated in the record.

The result does not show how the event experience compares with another treatment. The study had one group and no randomized comparator, so it does not estimate a relative treatment effect. It also does not establish whether an event was caused by treatment. Although the endpoint description includes drug-related events, the registry does not report a separate numerical result for that category, and the death is not identified as treatment-related.

The result should also be understood in light of participant selection. Eligibility required prior clinical benefit and an acceptable safety profile during earlier treatment, and participants came from parent studies. The observed experience therefore pertains to this continuation population; the record does not establish that the same pattern would apply to people with different treatment histories or eligibility characteristics.

Nor do the counts provide a complete account of event frequency over time, repeated events, severity gradations, or the timing of events. The registry does not report confidence intervals, a formal analysis of the primary endpoint, or detailed missing-data methods. The findings are consequently descriptive and limited to the reported summaries. They can inform understanding of what was recorded in this study, but they do not establish comparative safety, efficacy, or a causal treatment effect.

14. Why This Trial Matters Statistically

This study illustrates a statistical distinction between a safety description and a comparative treatment evaluation. A single-group continuation study can document adverse events among participants receiving ongoing treatment, but it has no randomized control group to provide a direct benchmark. The reported counts therefore answer a narrower question than a controlled trial would: what events were recorded in this selected group during the stated follow-up?

The rollover context also matters. Participants had previously received GSK2110183 and needed prior clinical benefit and an acceptable safety profile to be eligible. That design fits the stated goal of continued access, but it makes the resulting population different from an unselected group beginning treatment. A reader needs to keep that selection in mind when considering how widely the observations may apply.

The record also shows why outcome definitions deserve attention. The primary endpoint is described as participants with at least one adverse event, while its description includes drug-related events, serious events, events leading to discontinuation, and death. Those categories have different meanings. The posted numerical summaries do not separately quantify every category named in the endpoint description, so a broad endpoint label should not be mistaken for a complete breakdown of all safety outcomes.

Finally, the registry record is limited as a source of statistical detail. It does not report the analysis plan, missing-data methods, confidence intervals, or a trial-specific sample-size justification. Recognizing these omissions helps distinguish the recorded observations from conclusions the design and reporting cannot support. The study is statistically informative as a description of a continuation cohort, while remaining unsuitable for a randomized comparison of treatment effects.

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 limitation is the single-group, non-randomized design. With no control group, the adverse-event summaries cannot establish how the observed experience compares with another treatment or with a different course of care. The open-label design also means treatment was not masked, and the record does not describe whether outcome assessment included independent review.

The study population was selected from participants in parent studies. Eligibility required previous clinical benefit and an acceptable safety profile with GSK2110183. These criteria limit how far the observed safety experience can be generalized beyond people who met the rollover requirements. The registry also states that participants could have come from some combination studies, while excluding combination studies involving two investigational compounds; it does not give the distribution of participants by parent-study treatment or cohort.

The posted safety summaries are limited in detail. They give participant counts and selected serious-event terms, but the registry does not report event timing, duration, repeated-event detail, or separate numerical results for drug-related events and events leading to discontinuation. It reports 1 death but does not establish a treatment relationship. The record does not report confidence intervals, a formal primary-endpoint analysis, or detailed missing-data handling.

The primary endpoint timeframe extended from consent until the final study visit, up to approx. 76 months, but participant-level follow-up and exposure details are not reported. The record also does not provide a trial-specific sample-size justification or statistical analysis plan. These limitations mean the results should be treated as descriptive safety information for the recorded continuation population, not as evidence of comparative safety or treatment causality.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Continuation Study of the Oral AKT Inhibitor GSK2110183 — NCT01531894.
• Registry record last updated 2019-07-09; status last verified 2019-06.
• Results first posted 2019-07-09.
• 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

The registry describes a completed, phase 2, multicenter, open-label, non-randomized, single-group continuation study of GSK2110183, also called afuresertib, for participants with solid tumors and hematologic malignancies who had taken part in a parent study. Enrollment was 11. The study began on 2012-02-08, and primary completion was 2018-06-20.

The primary endpoint counted participants with at least one adverse event in the all-treated population, defined as participants who received at least one dose. The timeframe ran from consent to the final study visit, up to approx. 76 months. The adverse-event summary reports 11 participants with any adverse event, 2 with a serious adverse event, and 1 death. Gastritis and pneumonia are each listed among leading serious adverse-event terms at 9.1%.

No randomized control comparison is reported. The registry record does not report a statistical analysis plan, missing-data methods, confidence intervals, or separate numerical results for every safety category named in the endpoint description. The posted findings are descriptive and do not establish causation or comparative treatment effects.