Abemaciclib in Metastatic or Locally Advanced Anaplastic/Undifferentiated Thyroid Cancer: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Abemaciclib in Metastatic or Locally Advanced Anaplastic/Undifferentiated Thyroid Cancer (NCT04552769), a na phase 2 study. The primary outcome is Number of Participants With Overall Response (OR).

2. Clinical Question

The study asks whether treatment with abemaciclib is associated with an overall response in patients with metastatic or locally advanced anaplastic/undifferentiated thyroid cancer. The primary endpoint counts participants whose response is classified as complete or partial using RECIST v1.1 criteria. The planned assessment timeframe is 8 (+/-4) weeks from the start of treatment.

This is a treatment-evaluation question, not a randomized comparison of abemaciclib with another treatment or with no treatment. Without a comparator, the registry record cannot show how outcomes would have differed under another treatment strategy. The study also lists overall survival and progression-free survival as secondary outcomes, but their results are not reported in the registry record.

3. Trial Design

The registry describes a Phase 2, single-group study sponsored by Stanford University. It records the study as completed, with a start date of 2020-09-10 and a primary completion date of 2023-04-12. Enrollment is listed as 9. These design details describe the registered study; they do not establish how many participants contributed data to each endpoint.

All participants are assigned to the abemaciclib group in the registry description. The treatment is taken twice daily, with each cycle lasting 28 days. The treatment description states that cycles continue until progression or unacceptable toxicity develops. The registry records no masking and lists allocation as not applicable. No randomized control group is described, so the study is not a like-for-like treatment comparison.

The primary outcome is the number of participants with overall response, defined as complete response or partial response under RECIST v1.1. Its assessment timeframe is 8 (+/-4) weeks from the start of treatment. Overall survival and progression-free survival are listed as secondary outcomes. The record lists three outcome measures, but detailed results and analysis results are not reported in the registry record.

The registry does not report a sample-size justification, a detailed statistical analysis plan, or an interim-analysis plan. A single-group design can describe outcomes observed in the enrolled group, but it cannot by itself separate a treatment association from other explanations, such as the natural course of illness or differences in participant characteristics. Those limitations matter when interpreting any response count, even if one is available.

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 Number of Participants With Overall Response (OR), measured over 8 (+/-4) weeks from start of treatment.

The primary endpoint is the number of participants with overall response. A participant is counted as having an overall response if the assessment identifies either a complete response or a partial response using RECIST v1.1. The registry defines complete response for target lesions as disappearance of all target lesions, and partial response as at least a 30% decrease in the sum of the longest diameters of target lesions with no appearance of new lesions. It also describes complete response for non-target lesions as disappearance of all non-target lesions.

Response criteria provide a structured way to classify changes in disease findings. A predefined classification can support consistent assessment across participants and studies. The registry also describes persistent non-target lesions as incomplete response/stable disease and the appearance of new lesions as progressive disease. These definitions clarify the rules used to categorize response; they do not supply the observed response count.

The endpoint is a participant count, and the registry says it will be reported without dispersion. It is scheduled for assessment at 8 (+/-4) weeks from the start of treatment. The number of participants who met the response definition, the number assessed, and any uncertainty interval are not reported in the registry record. Without those results, the endpoint’s observed value and its precision cannot be evaluated.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry identifies a participant count as the primary endpoint. For a binary outcome such as whether a participant meets a response definition, a count records how many participants fall into the event category. To interpret such a count, readers generally also need the number assessed and a clear account of how missing or unevaluable outcomes were handled. Neither the primary response count nor its endpoint denominator is reported in the registry record.

What does a response count tell the reader?

A count is a direct description of the number of participants classified as having an event. It is not, by itself, a rate: a rate or proportion requires a denominator representing the relevant analysis group. Even when both are known, the observed proportion describes the study group and is subject to sampling variability. The registry specifies that this endpoint will be reported as a number without dispersion, and no uncertainty interval is reported in the registry record.

General statistical explanation: a confidence interval expresses uncertainty around an estimate under a specified statistical method and its assumptions. It is not a guarantee that the true value lies inside the interval, and it does not correct design limitations such as the absence of a comparator. No confidence interval for the primary endpoint is reported in the registry record, so the precision of an estimated response proportion cannot be assessed from the posted outcome information.

Why does the study design matter?

The registry calls the study single-group and records no masking. There is no randomized control group described. In general, randomization can help make groups comparable with respect to measured and unmeasured influences, while a comparator gives a reference for estimating differences in outcomes. Neither feature is described for this study. A single-group outcome can be useful as a description of the enrolled group, but it does not establish what would have happened to those participants under another treatment strategy.

The lack of masking can also be relevant in general. Knowledge of treatment assignment may influence some assessments or reporting, depending on how an outcome is measured. RECIST v1.1 provides stated response criteria, but the registry does not report whether imaging assessments were independently reviewed, whether assessors were blinded, or how disagreements were handled. These details are not reported in the registry record, so their role cannot be assessed.

How should the response definition be understood?

RECIST v1.1 turns observations about target and non-target lesions into categories. The registry identifies complete and partial response as the categories counted for overall response. Its description of partial response includes at least a 30% decrease in the sum of the longest diameters of target lesions and no new lesions. For non-target lesions, it describes disappearance as complete response and persistence of one or more lesions as incomplete response/stable disease; appearance of one or more new lesions is described as progressive disease.

These criteria make the endpoint more reproducible than an undefined judgment of improvement, but a classification still depends on assessment timing, available scans, and application of the rules. The planned timeframe is 8 (+/-4) weeks from treatment start. The registry does not report the actual assessment schedule, the number of evaluable scans, or how assessments outside that timeframe were treated.

What is known about statistical planning?

The registry does not report a sample-size justification or a detailed trial-specific statistical plan. It also does not report interim analyses. General explanation: sample-size calculations are planning exercises that depend on assumptions about the outcome, the effect to detect, the error rate, and the study design. A planning illustration is not evidence that the study had a particular probability of detecting an effect after it was conducted. The registry’s sample-size assumptions describe a two-arm, equal-allocation planning framework, while the trial itself is registered as single-group; such assumptions should not be mistaken for the actual design or for observed power.

For an outcome based on a count, statistical methods might model the event probability or describe the count and its uncertainty. The appropriate approach depends on the analysis population, denominator, missing data, and other design features. The registry does not report an analysis method, estimates, or analysis results. No specific model, adjustment, or inferential procedure can therefore be attributed to the trial from this record.

Overall survival and progression-free survival are time-to-event outcomes in general statistical practice. Their interpretation commonly depends on event definitions, follow-up duration, censoring rules, and the method used to estimate the outcome over time. The registry lists these outcomes but does not report their results or the relevant analysis details. No time-to-event estimate or comparison can be reconstructed from the information in 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("Abemaciclib")
n      <- c(9)
events <- c(0)
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  Abemaciclib  9  0  0.0  0.0  33.6  -0.0  29.9  0.3  30.8

11. Multiplicity, Missing Data and Analysis Populations

The registry lists a primary response outcome and names overall survival and progression-free survival as secondary outcomes. Considering several outcomes can raise multiplicity concerns: when many hypotheses are tested, the chance of at least one apparently notable result can increase. General statistical practice may address this through a prespecified outcome hierarchy or an adjustment to inference. The registry record does not report a multiplicity strategy, so it is not possible to determine whether or how such concerns were addressed.

The registry lists three outcome measures, but detailed analysis results are not reported. It does not describe a statistical analysis plan that specifies which outcomes were confirmatory, how secondary outcomes would be interpreted, or whether any adjustment was planned. Without those details and the outcome results, no conclusion about multiplicity-adjusted or unadjusted evidence can be drawn.

Missing-data handling is also not reported in the registry record. For the response endpoint, the number assessed, the number with unavailable assessments, and the treatment of unevaluable cases are not stated. For the listed survival outcomes, the registry does not report follow-up and censoring details. These omissions matter because the analysis population and the handling of incomplete observations can affect what an outcome estimate represents.

The record does not identify an intention-to-treat, per-protocol, or other analysis population. Enrollment is listed as 9, but it should not be assumed that every enrolled participant contributed to every endpoint. No participant flow or endpoint-specific denominator is 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: lung infection (22.2%), dysphagia (11.1%), tracheal obstruction (11.1%), anemia (11.1%), hallucinations (11.1%).

The registry records 9 participants at risk for serious adverse events in the abemaciclib group and 6 participants affected. For other adverse events, it records 9 at risk and 9 affected. It also records 7 deaths. These figures are descriptive safety counts in the registry record; they do not, on their own, establish that treatment caused an event or death.

The listed serious-event terms and percentages are lung infection, 22.2%; dysphagia, 11.1%; tracheal obstruction, 11.1%; anemia, 11.1%; hallucinations, 11.1%; and stridor, 11.1%. The registry presents these as serious adverse-event terms. The percentages should be read as the reported values, not as evidence about causality or comparative risk. A comparator group is not described.

The registry record does not report the timing, duration, severity grading, attribution, or outcome of each event, nor does it explain how the event-term percentages were derived. The death count is not identified as deaths caused by adverse events or by treatment. These missing details limit interpretation of the safety profile and prevent comparison with another treatment group.

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

The record establishes that a completed Phase 2, single-group study of abemaciclib was registered for metastatic or locally advanced anaplastic/undifferentiated thyroid cancer. It describes a twice-daily treatment schedule in 28-day cycles, continuing until progression or unacceptable toxicity develops. It also defines overall response using RECIST v1.1 and specifies an assessment timeframe of 8 (+/-4) weeks from treatment start.

Those design details clarify what the study intended to evaluate, but they are not outcome findings. The primary response count is not reported in the registry record. Results for the listed secondary outcomes, overall survival and progression-free survival, are also not reported. Therefore, the posted record does not show how many participants responded, how long participants remained free of progression, or how long they survived.

Likewise, the registry’s safety counts describe reported events in the study group but do not establish treatment causation. Because there is no comparator group, the record cannot quantify how outcomes differ from another treatment strategy. It also does not report enough detail about event timing, attribution, follow-up, or outcome denominators to resolve those questions.

General statistical principle: an observed outcome and the strength of evidence for a treatment effect are different matters. An outcome estimate needs a defined analysis population and an account of uncertainty; a causal comparison additionally depends on a design and assumptions that support comparison. The registry record does not report the endpoint results, uncertainty measures, or a comparative design for estimating a treatment effect.

The appropriate reading is therefore limited: the record documents the planned question, design, treatment schedule, endpoint definition, and selected safety figures. It does not support a conclusion that abemaciclib does or does not produce an overall response, nor does it provide a comparative efficacy estimate. The absent outcome values should not be interpreted as zero events or as evidence of no effect.

14. Why This Trial Matters Statistically

This trial is statistically notable because it frames a clearly specified response question in a single-group Phase 2 design. A participant-level endpoint based on RECIST v1.1 gives a defined basis for classifying complete and partial response, and a stated assessment timeframe helps identify when that classification is intended to occur. Those features are important for understanding the intended measurement.

The study also illustrates the distinction between a planned endpoint and a reported result. The registry defines the primary outcome as a count without dispersion, but the count itself is not reported in the registry record. With no result, denominator, or uncertainty measure, readers cannot assess the observed response frequency or its precision. This is a limitation of the available record, not evidence that no response occurred.

The single-group design is equally important. An outcome in the treated group can describe that group, but a control group is needed for a direct comparison of outcome patterns under different treatment strategies. The registry records no comparator and no masking. These design features constrain causal interpretation even when outcome data are available.

Finally, the listed serious adverse-event figures make clear why safety counts need context. Counts and percentages are descriptive unless event definitions, follow-up, attribution, and an appropriate comparison are also understood. Those details are not reported in the registry record. The trial therefore provides a useful example of how endpoint definition and study design shape what can be learned, while the unreported efficacy results limit any assessment of outcomes.

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 most direct limitation is that the primary endpoint result is not reported in the registry record. The number assessed for response, the endpoint denominator, and an uncertainty measure are also not reported. Although enrollment is listed as 9, enrollment does not establish how many participants had an evaluable response assessment.

The single-group design has no comparator described, so the registry cannot provide a randomized estimate of an outcome difference between treatments. No masking is reported. The registry does not describe independent response review or other safeguards that might clarify how assessments were conducted.

The record identifies an assessment timeframe of 8 (+/-4) weeks but does not report actual assessment timing, follow-up completeness, or handling of missing or unevaluable data. It lists overall survival and progression-free survival as secondary outcomes but does not report their results, event definitions in detail, follow-up, or censoring methods.

The registry does not report a detailed statistical analysis plan, sample-size justification, interim-analysis plan, analysis population, or multiplicity strategy. The safety record gives selected counts and event-term percentages but does not report event attribution, timing, severity grading, or the circumstances surrounding the deaths. These omissions limit interpretation of both efficacy and safety and prevent a fuller assessment of the analyses.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Abemaciclib in Metastatic or Locally Advanced Anaplastic/Undifferentiated Thyroid Cancer — NCT04552769.
• Registry record last updated 2025-06-05; status last verified 2025-06.
• Results first posted 2024-09-19.
• 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 NCT04552769 as a completed Phase 2, single-group study sponsored by Stanford University, with enrollment of 9. Its dates are 2020-09-10 for study start and 2023-04-12 for primary completion. Participants received abemaciclib twice daily in 28-day cycles until progression or unacceptable toxicity developed.

The primary endpoint is the number of participants with complete or partial response under RECIST v1.1, assessed at 8 (+/-4) weeks from treatment start. Overall survival and progression-free survival are listed as secondary outcomes. The primary and secondary outcome results are not reported in the registry record.

The registry records 6 participants affected by serious adverse events, 9 affected by other adverse events, and 7 deaths in the abemaciclib group. These safety figures are descriptive and do not establish causation. No comparator is described, and further analysis and follow-up details are not reported in the registry record.