This page provides an independent statistical analysis and educational interpretation of publicly reported results. ClinicalTrials.gov provides the official trial registry record. Numerical trial results on this page are restricted to the results posted in the ClinicalTrials.gov record; calculations added by Clinical Biostats are labelled as such.
1. Trial at a Glance
This page covers the registry results for Pembrolizumab in Anaplastic/Undifferentiated Thyroid Cancer (NCT02688608), a na phase 2 study. The primary outcome is Overall Response (OR).
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT02688608 |
| Phase | Phase 2 |
| Condition | Anaplastic Thyroid Cancer |
| Allocation | Not applicable (single group) |
| Design model | Single Group |
| Masking | None (open label) |
| Enrollment | 6 |
| Arms in the primary outcome | n/a |
| Lead sponsor | Saad A Khan |
| Results posted | Yes |
2. Clinical Question
Population
The study concerned people with metastatic or locally advanced anaplastic/undifferentiated thyroid cancer. The registry lists anaplastic thyroid cancer as the condition and records enrollment of 6 participants. It also states that response assessment data were not obtained for all participants, so the number with assessable response may not equal the number enrolled.
Intervention
The intervention was pembrolizumab, given intravenously at 200 milligrams every 3 weeks. The registry describes this as the study treatment and records a single pembrolizumab group.
Comparator
There was no comparator group in the registry design. Allocation is listed as not applicable, the model is single group, and masking is none. Consequently, the posted results cannot make a randomized, like-for-like comparison between pembrolizumab and another treatment or a control condition.
Primary question
The primary outcome was overall response: participants achieving complete response or partial response under RECIST v1.1. The registry describes response within 18 months, while its outcome description also says the cumulative count is participants who achieve complete or partial response within 6 months. This difference in the stated response period needs to be kept in view. A numerical response count is not reported in the registry record, so the primary question cannot be answered from the posted outcome information alone.
3. Trial Design
This was a Phase II, single-group trial of pembrolizumab for metastatic or locally advanced anaplastic/undifferentiated thyroid cancer. The registry records 6 participants enrolled and identifies the study as completed. The start date is 2016-10 and the primary completion date is 2020-10. The sponsor is Saad A Khan.
All participants were assigned to the pembrolizumab group; the intervention description specifies 200 milligrams intravenously every 3 weeks. Allocation is listed as not applicable, masking as none, and the model as single group. There is no control arm described in the record, so outcomes are not presented as a randomized comparison. A protocol-level account of treatment modifications, follow-up schedules beyond the stated endpoint period, or other operational details is not reported in the registry record.
The primary outcome was overall response, defined by complete or partial response under RECIST v1.1. The listed secondary outcomes were progression-free survival, adverse events associated with pembrolizumab, and overall survival. The record lists 4 outcome measures, but records no analyses. It does not report a numerical primary response result or numerical results for the listed secondary outcomes. Safety information is recorded separately, including counts for participants at risk and affected and a list of serious adverse-event terms.
A single-group design can describe outcomes observed among participants who received study treatment, but without a comparator it cannot isolate the treatment’s effect from other explanations for those outcomes. That distinction matters especially when reading response and safety information from a small enrolled group. The registry record does not report a sample-size justification, interim-analysis plan, or statistical analysis plan.
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
| Stage | Pembrolizumab |
|---|---|
| STARTED | 6 |
| COMPLETED | 5 |
| NOT COMPLETED | 1 |
Reasons for not completing this period:
| Reason | Pembrolizumab |
|---|---|
| Lost to Follow-up | 1 |
Analysis population for the primary outcome, as defined in the registry: Response assessment data was not obtained for all participants.
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.
| Characteristic | Unit | Pembrolizumab |
|---|---|---|
| Participants analysed | 6 | |
| Age, Categorical: <=18 years | Participants | 0 |
| Age, Categorical: Between 18 and 65 years | Participants | 6 |
| Age, Categorical: >=65 years | Participants | 0 |
| Sex: Female, Male: Female | Participants | 5 |
| Sex: Female, Male: Male | Participants | 1 |
| Ethnicity (NIH/OMB): Hispanic or Latino | Participants | 0 |
| Ethnicity (NIH/OMB): Not Hispanic or Latino | Participants | 6 |
| Ethnicity (NIH/OMB): Unknown or Not Reported | Participants | 0 |
| Race (NIH/OMB): American Indian or Alaska Native | Participants | 0 |
| Race (NIH/OMB): Asian | Participants | 0 |
| Race (NIH/OMB): Native Hawaiian or Other Pacific Islander | Participants | 0 |
| Race (NIH/OMB): Black or African American | Participants | 0 |
| Race (NIH/OMB): White | Participants | 4 |
| Race (NIH/OMB): More than one race | Participants | 0 |
| Race (NIH/OMB): Unknown or Not Reported | Participants | 2 |
| Region of Enrollment: United States | participants | 6 |
6. Primary Endpoint
The registry lists the primary outcome as Overall Response (OR), measured over up to 18 months..
| Element | Registry entry |
|---|---|
| Result type | Count Of Participants |
| Measure of spread | not applicable |
| Unit | Participants |
| Endpoint classification | Binary Endpoint |
The primary endpoint was overall response, a binary outcome at the participant level: a participant either achieved complete or partial response, or did not meet either response category. Under RECIST v1.1, complete response is disappearance of all target lesions. Partial response is a decrease of at least 30% in the sum of the longest diameters of target lesions. The record defines overall response as complete response plus partial response. It also describes progressive disease as a 20% increase in that sum and/or the appearance of one or more new lesions; stable disease refers to changes that do not meet the other stated criteria.
Response is used as a measure of tumor change under specified assessment criteria. A count of participants meeting the response definition is more interpretable when the assessment period and the population included in the count are clear. In this record, the primary outcome timeframe is listed as up to 18 months, the definition refers to response within 18 months, and the outcome description says the cumulative number is those achieving response within 6 months. The record also notes that response assessment data were not obtained for all participants.
No numerical overall-response count is reported in the registry record. The outcome is described as a cumulative number without a measure of dispersion, so the registry text does not provide an estimate of uncertainty around a response proportion. The absent result and the incomplete response assessments limit what can be concluded about the primary endpoint.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The registry describes a completed Phase II study with 6 participants enrolled in a single pembrolizumab group. Its primary endpoint is overall response according to RECIST v1.1, but a numerical count of participants with complete or partial response is not reported in the registry record. Therefore, the posted information does not establish how many participants met the primary response definition or how precisely any response frequency was estimated.
Interpretation is further complicated by the endpoint timing language. The timeframe is listed as up to 18 months and the response definition refers to the 18-month period, while the outcome description states that the cumulative number concerns response within 6 months. These are not identical descriptions of the assessment window. The record does not clarify the difference. It also states that response assessment data were not obtained for all participants, without specifying how missing assessments were handled or how many participants contributed to the endpoint.
The safety record lists 6 participants at risk and 6 affected for serious adverse events, and 6 at risk and 6 affected for other adverse events. It lists serious-event terms with reported percentages, including neoplasm, other—disease progression at 83.3%, dyspnea at 50.0%, mucositis, oral at 33.3%, rash at 33.3%, respiratory failure at 33.3%, and leukocytosis at 16.7%. The record also lists 5 deaths. These figures describe events recorded in this group; they do not, on their own, show that pembrolizumab caused an event or death. The record does not provide the timing or causes of the deaths in this safety summary.
Progression-free survival and overall survival are listed as secondary outcomes, but numerical results for them are not reported in the registry record. No analyses are recorded. As a result, there are no posted estimates of treatment effect, uncertainty intervals, or hypothesis tests to interpret for those outcomes. The single-group design also means there is no contemporaneous comparison group against which the observed outcomes could be contrasted.
Overall, the registry record supports a description of the planned response definition, the study structure, and selected safety counts. It does not support a numerical estimate of primary response from the outcome information recorded. The small enrolled group and the incomplete response assessments add uncertainty, while the absence of a comparator limits causal interpretation even if outcome estimates were available.
9. Statistical Methods Explained
The primary outcome is a participant-level binary endpoint. Each participant is classified according to whether the specified response criterion was met during the stated assessment period. The registry defines overall response as complete response or partial response under RECIST v1.1. This kind of endpoint is often reported as a count, with the relevant denominator needed to understand how common the outcome was in the analyzed group. The registry record does not report the primary response count or the number included in its calculation.
What does a binary response count tell the reader?
General statistical explanation: a count gives the number of participants meeting a definition, but it does not by itself convey the precision of an estimate. A proportion can be estimated only when both the count and its denominator are known. A confidence interval is a range of values compatible with the observed data under a specified statistical method; it communicates uncertainty around an estimate rather than guaranteeing that the true value lies in that range. No response estimate or confidence interval is reported in the registry record.
The response criteria define how changes in target lesions are categorized. Complete response means disappearance of all target lesions. Partial response requires at least a 30% decrease in the sum of the longest diameters of target lesions. Progressive disease is described as a 20% increase in that sum and/or new lesions. Stable disease comprises changes that do not meet those criteria. Using prespecified categories can make assessments more consistent, but the registry record does not describe assessment review procedures or how disagreements, if any, were resolved.
Why do the assessment window and missing assessments matter?
The record gives more than one time reference for overall response: the primary outcome timeframe is up to 18 months, the response definition specifies 18 months, and the cumulative count description says within 6 months. A result tied to one assessment period need not answer the question for another period. The registry record does not clarify which period was used for the reported count. It also states that response assessment data were not obtained for all participants. General statistical explanation: when outcome data are missing, the analyzed participants may differ from those without an assessment. The direction and size of any resulting bias depend on why data are missing and how the analysis treats them; those details are not reported in the registry record.
The outcome is recorded as a count without a dispersion measure. For a binary endpoint, uncertainty is commonly conveyed through an interval estimate around a proportion, but no such estimate is reported. The registry also lists no analyses. It therefore provides no model-based estimate, adjustment strategy, test result, or account of how participants without response assessments entered the analysis.
How should the design and planning illustrations be understood?
The study is a single-group trial, with no randomized comparator. General statistical explanation: randomization supports a balanced comparison, on average, of measured and unmeasured characteristics between treatment groups. Without a concurrent comparison group, changes during follow-up cannot be separated from other possible influences by a treatment contrast. A response count in a single group can describe what was recorded among participants, but cannot by itself establish the causal effect of treatment.
Any sample-size figures associated with planning are illustrations, not observed power. The stated planning assumptions use a two-sided significance level of 0.05, equal allocation between two arms, a normal approximation, and an effect defined as a stated fraction of the observed effect. Those assumptions describe a hypothetical two-arm planning exercise, not the single-group design recorded for this trial. For non-time-to-event outcomes, such illustrations are expressed as participants per arm for 80% power or participants per arm for 90% power; time-to-event illustrations are expressed as total events. The registry record does not report the trial’s own sample-size justification, and the calculated planning values are not reported in the registry record.
General statistical explanation: over-dispersion means that observed variability is greater than a statistical model expects. It can make standard errors too small if the model does not account for that extra variability. The primary endpoint is a count of participants meeting a binary response definition, and the record reports no dispersion estimate or analysis model. Over-dispersion is therefore a general concept rather than a feature documented for this endpoint.
Finally, statistical significance and clinical importance are different ideas. A significance test evaluates data against a specified null model; an effect estimate and its uncertainty describe magnitude and precision. Neither can be interpreted without the relevant result and analysis details. The registry record lists no analyses and no numerical primary outcome, so such judgments cannot be made from the posted information.
10. Multiplicity, Missing Data and Analysis Populations
The registry lists overall response as the primary outcome and names progression-free survival, adverse events associated with pembrolizumab, and overall survival as secondary outcomes. It also records 4 outcome measures and 0 analyses. The record does not report how many statistical hypotheses were tested, whether any multiplicity adjustment was planned, or whether a hierarchy among outcomes was used. Those procedures are not reported in the registry record, so no claim can be made about how the chance of false-positive findings across multiple outcomes was controlled.
Response assessment data were not obtained for all participants. The registry record does not state the number with missing response assessments, the reasons for missingness, the population used for the primary endpoint, or a method for handling missing data. It also does not describe whether participants who did not have an assessment were counted as nonresponders, excluded, or handled in another way. These details affect the denominator and interpretation of a response count.
The primary endpoint’s time window is described inconsistently: the outcome timeframe is up to 18 months, the definition refers to 18 months, and the cumulative-count description refers to 6 months. The record does not explain how this difference was resolved. Numerical results for the primary endpoint and named secondary outcomes are not reported in the registry record, and no analyses are listed. A protocol-defined analysis population, analysis plan, interim analysis plan, and missing-data sensitivity analyses are also not reported in the registry record.
11. Safety Results
The registry reports serious adverse events as affected participants divided by participants at risk.
| Arm | Participants with serious adverse events | Participants at risk | Percentage |
|---|---|---|---|
| Pembrolizumab | 6 | 6 | 100.0% |
Deaths
| Arm | Deaths (participants affected of at risk) |
|---|---|
| Pembrolizumab | 5 of 6 |
Other (non-serious) adverse events
Participants with at least one non-serious event at or above the registry's 0% reporting threshold.
| Arm | Participants affected of at risk |
|---|---|
| Pembrolizumab | 6 of 6 |
Most frequent serious adverse event terms
| Event term | Organ system | Pembrolizumab |
|---|---|---|
| Neoplasm, other - disease progression | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | 5 of 6 |
| Dyspnea | Respiratory, thoracic and mediastinal disorders | 3 of 6 |
| Mucositis, oral | Gastrointestinal disorders | 2 of 6 |
| Rash | General disorders | 2 of 6 |
| Respiratory failure | Respiratory, thoracic and mediastinal disorders | 2 of 6 |
| Leukocytosis | Blood and lymphatic system disorders | 1 of 6 |
| Pain | General disorders | 1 of 6 |
| Parietal mass, right front | Nervous system disorders | 1 of 6 |
| Pneumonia | Respiratory, thoracic and mediastinal disorders | 1 of 6 |
| Pneumonia, aspiration | Respiratory, thoracic and mediastinal disorders | 1 of 6 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Pembrolizumab |
|---|---|---|
| Fatigue | General disorders | 6 of 6 |
| Hypertension | Vascular disorders | 6 of 6 |
| Shortness of breath | Respiratory, thoracic and mediastinal disorders | 5 of 6 |
| Anemia | Blood and lymphatic system disorders | 4 of 6 |
| Trouble swallowing | Gastrointestinal disorders | 4 of 6 |
| Cough | Respiratory, thoracic and mediastinal disorders | 4 of 6 |
| Leg swelling | General disorders | 3 of 6 |
| Bruising | Injury, poisoning and procedural complications | 3 of 6 |
| Arthritis (joint inflamation) | Musculoskeletal and connective tissue disorders | 3 of 6 |
| Back Pain | Musculoskeletal and connective tissue disorders | 3 of 6 |
Serious events with the highest arm-level rate: neoplasm, other - disease progression (83.3%), dyspnea (50.0%), mucositis, oral (33.3%), rash (33.3%), respiratory failure (33.3%).
The registry safety information lists 6 participants at risk and 6 affected for serious adverse events. It also lists 6 at risk and 6 affected for other adverse events. The serious-event terms include neoplasm, other—disease progression at 83.3%, dyspnea at 50.0%, mucositis, oral at 33.3%, rash at 33.3%, respiratory failure at 33.3%, and leukocytosis at 16.7%. The record lists 5 deaths.
These are safety counts and listed term frequencies for the pembrolizumab group. The record does not give event timing, duration, severity details for each event, or a breakdown of the listed terms by participant. Terms may describe overlapping events or participants; the record does not explain this in the safety summary. The percentages should therefore be read as recorded frequencies, not added together or treated as mutually exclusive categories.
General statistical explanation: adverse events observed during a trial do not automatically establish that the study treatment caused them. The record does not provide a control group for comparison, and the safety counts alone cannot separate treatment-related events from events due to the disease or other causes. The listed death count does not identify causes or establish treatment attribution.
12. What the Result Does, and Does Not, Mean
The record identifies an important statistical question: how many participants in this single-group study met the prespecified definition of overall response, and how uncertain is that estimate? The posted registry information does not include a numerical response result, so neither the response frequency nor its precision can be described. The time window is also not consistently stated, and response assessment data were not obtained for all participants.
The safety summary documents participants affected by serious and other adverse events and lists selected serious-event terms. It also records 5 deaths. These observations are relevant to describing what occurred in the group, but they do not establish that pembrolizumab caused any particular event or death. There is no randomized comparator in the recorded design, and the safety summary does not provide timing or cause-of-death details.
The absence of a comparator is a central limit on interpretation. Even if a response count were available, a single-group result would not show how outcomes would have differed under another treatment or no study treatment. The record also does not report numerical progression-free survival or overall survival results, despite listing them as secondary outcomes.
Accordingly, the registry record describes the trial question, endpoint definitions, design, and selected safety counts, but it does not provide enough outcome information to quantify the primary response result or compare treatment effects. These statements characterize the information recorded; they are not advice about treatment.
13. Why This Trial Matters Statistically
The trial concerns anaplastic thyroid cancer, and the registry summary describes an urgent need for treatment approaches and trials designed for this condition. Statistically, the record illustrates the challenge of interpreting evidence from a small, single-group study when the primary result is not numerically reported. The enrollment was 6, and response assessments were not obtained for all participants. Those details make clarity about the endpoint denominator and missing-data handling particularly important.
The endpoint definition is specific: overall response combines complete and partial response under RECIST v1.1. Clear criteria help define what counts as a response, but they do not resolve uncertainty about the time window. The registry uses both 18 months and 6 months in describing the outcome. Reporting the assessment period and the number of participants evaluated would be needed to interpret a response count in context.
The design also matters. A single-group study can describe outcomes in its participants, but it cannot make a randomized comparison or directly separate treatment effects from other causes. That limitation applies to both response and safety interpretation. The listed serious adverse-event frequencies and death count are useful descriptive observations, not comparative estimates of risk or proof of causation.
The record names secondary outcomes but provides no analyses and no numerical results for the primary or secondary endpoints. This makes the difference between a planned outcome and a reported result especially important: an endpoint definition alone does not establish what happened. In this case, the registry record leaves the central response estimate and its precision unavailable.
14. 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 endpoint limitation is that a numerical overall-response result is not reported in the registry record. The response outcome is described with two different assessment periods: up to 18 months and within 6 months. The record does not clarify which period applies to the cumulative count. It also states that response assessment data were not obtained for all participants, but does not report how many were assessed, why data were missing, or how missing assessments were handled.
The study is recorded as a single-group trial with no comparator and no masking. This design does not permit a randomized comparison. Enrollment was 6, and the record lists no analyses. Numerical results for progression-free survival and overall survival are not reported in the registry record, although both are named as secondary outcomes.
The safety summary gives affected-participant counts, listed serious-event percentages, and a death count, but does not report event timing or causes of death. It does not establish that events were caused by pembrolizumab. The record also does not report the trial’s sample-size justification, interim analyses, or statistical analysis plan. These omissions limit assessment of how outcomes were planned, analyzed, and interpreted; they should not be filled in by assumption.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Pembrolizumab in Anaplastic/Undifferentiated Thyroid Cancer — NCT02688608.
- Registry record last updated 2022-02-10; status last verified 2022-02.
- Results first posted 2022-02-10.
- 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.
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18. Record Summary
This completed Phase II study enrolled 6 participants with metastatic or locally advanced anaplastic/undifferentiated thyroid cancer in a single pembrolizumab group. The treatment description specifies 200 milligrams intravenously every 3 weeks. Allocation is listed as not applicable, and masking as none. The recorded start date is 2016-10 and the primary completion date is 2020-10.
The primary outcome was overall response by RECIST v1.1, combining complete and partial response. Its timing is described as both within 18 months and within 6 months. The record states that response assessment data were not obtained for all participants, but does not report a numerical response count. Progression-free survival, adverse events associated with pembrolizumab, and overall survival are listed as secondary outcomes, with no analyses recorded.
The safety summary lists 6 participants affected by serious adverse events, 6 affected by other adverse events, selected serious-event term frequencies, and 5 deaths. These are descriptive registry entries and do not establish causation. A comparator, numerical primary result, and numerical secondary outcome results are not reported in the registry record.