Ponatinib for Squamous Cell Lung and Head and Neck Cancers: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Ponatinib for Squamous Cell Lung and Head and Neck Cancers (NCT01761747), a na phase 2, phase 3 study. The primary outcome is Response Rate of Patients With Lung or Head and Neck SCC Treated With Ponatinib.

2. Clinical Question

The clinical question is about tumor response in a selected population, not about ponatinib in all people with lung or head and neck cancer. Eligibility depended on an experimental tumor test finding a required FGFR kinase alteration. The study also listed secondary questions about FGFR alteration prevalence, progression-free survival, overall survival, disease control, toxicities, and correlations between tumor alterations and participant characteristics. Those questions do not replace the primary response-rate question, and their results are not reported in the registry record.

3. Trial Design

The registry record describes a single-group study of ponatinib for advanced lung and head and neck cancers with FGFR kinase alterations. It lists the study phase as Phase II and Phase III. The allocation field is not applicable, masking is none, and the recorded model is single group. No concurrent control group or randomized treatment allocation is described.

The intervention was ponatinib taken by mouth daily. The study description says participants needed a tumor with a required FGFR kinase alteration, identified using an experimental test on tumor tissue. The record reports enrollment of 3. Its status is terminated; the recorded start was 2013-01, and primary completion was 2014-06. The reason for termination is not reported in the registry record.

The primary outcome was the response rate among people with previously treated lung or head and neck SCC. Response was defined as an investigator-assessed confirmed complete response or partial response under RECIST v1.0, with the outcome timeframe listed as 2 years. Secondary outcomes included prevalence of specific FGFR amplifications or mutations, progression-free survival, overall survival, disease control, toxicities, and associations involving participant characteristics and tumor alterations. Although these outcomes are listed, their numerical results are not reported in the registry record.

A single-group design can describe what was observed among treated participants, but it cannot directly estimate a treatment contrast against a concurrent control group. The record does not report a statistical analysis plan, details of outcome assessment beyond the primary endpoint description, or the reason the study stopped. The phase labels alone do not establish what analyses were planned or completed.

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 Response Rate of Patients With Lung or Head and Neck SCC Treated With Ponatinib, measured over 2 years.

The primary endpoint is the response rate: the percentage of participants with an investigator-assessed confirmed complete response (CR) or partial response (PR). Under the RECIST v1.0 description, a CR means disappearance of all target lesions. A PR means a >=30% decrease in the sum of the longest diameters of target lesions. Overall response is defined as CR plus PR. The registry record says the assessment used MRI and gives a timeframe of 2 years.

A response endpoint provides a way to summarize whether tumors met prespecified imaging criteria during the stated assessment period. Combining complete and partial responses into an overall response measure can capture more than disappearance of all target lesions alone. The endpoint is defined using both a measurement rule and an assessment process: investigators assess target lesions and classify whether the criteria for confirmed CR or PR are met.

The record does not report how many participants had a confirmed response, the number assessed for response, or the resulting percentage. It also does not provide confidence intervals or a statistical test for the primary endpoint. As a result, the endpoint definition can be explained, but the observed response rate and its precision cannot be evaluated from the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

General: A clinical endpoint is the outcome chosen to answer a study question. Here, the primary endpoint is a response proportion based on the number of participants classified as having a confirmed complete response or partial response. A proportion is interpretable only when the numerator, the number meeting the response definition, and the denominator, the group evaluated for response, are both clear. The registry record defines the endpoint but does not report either the response count or the response-rate estimate.

What does a response definition contribute?

General: A prespecified response definition makes outcome classification more consistent. RECIST v1.0 specifies criteria for classifying changes in target lesions. In this record, complete response means disappearance of all target lesions, and partial response means a >=30% decrease in the sum of the longest diameters of target lesions. The record defines overall response as CR plus PR and describes investigator assessment using MRI. A clear rule can reduce ambiguity about what counts as response, but it does not by itself show how consistently assessments were conducted or whether all participants had evaluable imaging. Those details are not reported in the registry record.

How should uncertainty be understood?

General: A confidence interval describes the range of estimates compatible with the observed data under a statistical method and its assumptions. It communicates precision as well as the point estimate. In small studies, estimates can be imprecise because each participant’s outcome has a large influence on the proportion. No confidence interval for the primary response rate is reported in the registry record, and no response rate is reported from which a reader could evaluate precision. The number enrolled is 3, but that alone does not provide the missing endpoint denominator: the record does not state how many participants were assessed for the primary outcome.

General: A hypothesis test and a confidence interval answer related but different questions. A test evaluates data relative to a specified null hypothesis, while an interval describes uncertainty around an estimate. Neither can be reconstructed responsibly without the outcome data and a specified analysis approach. The registry record lists no analyses. The statistical plan, including any testing procedure for the primary outcome, is not reported in the registry record.

What does the study design imply?

General: A single-group study can estimate outcomes among the participants treated under the study conditions. Without a control group, it does not directly estimate how those outcomes would compare with outcomes under another treatment or no study treatment. A randomized comparison is one approach to making treatment groups more comparable with respect to measured and unmeasured factors; this study is not described as randomized and has no listed comparator. Accordingly, a response proportion from this design would be descriptive rather than a randomized estimate of a treatment contrast.

General: Enrollment and analysis populations can differ. Some enrolled participants may not have a recorded outcome for a particular endpoint, and a registry may report an outcome using a specified analysis population. The record does not report the primary endpoint population, missing outcome counts, or how missing response assessments were handled. The enrollment figure should not be assumed to equal the endpoint denominator.

How should planning illustrations be read?

General: Sample-size planning asks how much information a future study might need to detect a chosen effect under stated assumptions. A planning calculation depends on the target effect, significance level, power target, allocation, and statistical model. Such a calculation is not a measurement of the current study’s success and is not observed power. The stated planning assumptions for illustrations associated with the results are a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation; the effect to detect is described as a fraction of the observed effect. Time-to-event illustrations are described as totals of events, while other illustrations are described as participants per arm. These assumptions do not match the recorded single-group design, and the illustrations should not be interpreted as the trial’s actual design or as evidence about the primary result.

General: Over-dispersion is variation greater than a simple statistical model expects. When present, standard errors based on an under-dispersed model can be too small, making intervals appear too precise and tests overly optimistic. The registry record does not report a model for the primary response outcome, a dispersion estimate, or a reason to apply an over-dispersion adjustment. It would therefore be inappropriate to claim that such an adjustment was used or needed in this analysis.

What analyses are documented?

The registry record lists no statistical analyses. It does not report a primary response estimate, confidence interval, p-value, model, covariate adjustment, or interim analysis. Whether these methods were planned or used is not reported in the registry record. The absence of those details prevents an assessment of how the primary response question was analyzed. General statistical explanations describe methods that may be relevant to clinical studies; they should not be mistaken for methods documented for this trial.

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("Ponatinib Treatment Arm")
n      <- c(3)
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  Ponatinib Treatment Arm  3  0  0.0  0.0  70.8  0.0  56.1  0.6  60.2

11. Multiplicity, Missing Data and Analysis Populations

The registry record lists a primary response-rate outcome and multiple secondary outcomes, including FGFR alteration prevalence, progression-free survival, overall survival, disease control, toxicities, and correlations involving participant characteristics and FGFR alterations. It does not report a statistical analysis plan, a hierarchy for testing outcomes, or any adjustment for multiple comparisons. Whether multiplicity procedures were planned or used is not reported in the registry record.

General: When a study examines many outcomes or subgroup relationships, the chance of at least one apparently unusual result can increase if each is evaluated independently. A prespecified testing strategy can help clarify which questions are confirmatory and how evidence across outcomes should be interpreted. Without a reported plan or analysis, the listed secondary outcomes should be treated as questions the study intended to examine, not as findings.

The registry record does not report missing primary outcome data, the number assessed for response, or an analysis population. It also does not describe whether participants without an evaluable assessment were excluded, classified in another way, or handled using a missing-data method. These omissions matter because the response proportion depends on both the outcome count and the denominator used.

Enrollment was 3, but that figure cannot establish the number included in any specific outcome analysis. No results are reported for the listed secondary outcomes, and no analyses are listed. Accordingly, missing-data handling, multiplicity control, and the extent to which any planned outcome analyses were completed are not reported in the registry record.

12. Safety Results

The registry reports serious adverse events as affected participants divided by participants at risk.

Other (non-serious) adverse events

Participants with at least one non-serious event at or above the registry's 0% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: pancreatits (50.0%).

The adverse-event record lists a Ponatinib Treatment Arm with 2 participants at risk for serious adverse events and 1 affected. For other adverse events, it lists 2 at risk and 2 affected. The top serious adverse term is recorded as “Pancreatits” at 50.0%. These figures describe the entries in this registry record; they do not provide a detailed account of event timing, severity grades, duration, recurrence, or the method used to decide whether an event was related to ponatinib.

The affected counts should not be added together to infer the number of participants with any adverse event, because the record does not say whether the categories overlap. The term and percentage also do not establish the number of events or the denominator used for that particular term beyond what the registry record states. With enrollment of 3 and only 2 listed at risk in each adverse-event category, these safety entries are limited and do not give a precise estimate of event frequency in a broader population.

Deaths are not reported in the adverse-event field. That is different from a report of no deaths. The record does not provide further safety analysis or an explanation of the termination status.

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

The record establishes that a study of ponatinib was registered for people with previously treated lung or head and neck SCC with a required FGFR kinase alteration. It describes a daily oral intervention, a single-group design, enrollment of 3, and a primary endpoint based on confirmed complete or partial response under RECIST v1.0. It also provides limited adverse-event counts and a serious adverse term.

It does not establish the observed response rate. The primary result is not reported in the registry record, and the response count, analysis denominator, and uncertainty interval are absent. The absence of a reported response result does not mean that no participant responded; it means the record does not state the outcome. Results for the secondary outcomes are also not reported.

Even if a response proportion were available, the single-group design would describe outcomes among treated participants rather than compare ponatinib with a control condition. The registry record does not describe randomized allocation or a comparator. A descriptive outcome in this design cannot, by itself, establish what would have happened to similar participants under another treatment or without ponatinib.

The adverse-event entries should also be read narrowly. They are counts from the registry record, not precise risk estimates for a wider population. The record does not explain the reason for termination, report deaths in the adverse-event field, or provide details needed to interpret event timing or attribution. Therefore, the posted information supports a description of the study and its limited recorded outcomes, but not a conclusion about the magnitude or reliability of a treatment effect or the full safety profile.

14. Why This Trial Matters Statistically

This trial is statistically notable for the gap between a clearly defined primary endpoint and the absence of a reported primary result. The registry record specifies response criteria and an assessment timeframe, but it does not provide the response numerator, denominator, estimate, or uncertainty interval. This illustrates why endpoint definitions alone are not enough to evaluate a clinical finding: the observed data and analysis population are also needed.

The study’s single-group structure is important for interpretation. A response proportion can describe outcomes among treated participants, but without a comparator it does not directly quantify a contrast between treatments. The record’s limited enrollment of 3 further means that any participant-level outcome could have a large influence on a descriptive estimate, although no estimate is posted for this endpoint.

The termination status and absence of reported analyses also leave questions unresolved. The reason for termination, missing-outcome handling, and whether planned secondary analyses were completed are not reported in the registry record. These are not details that can be inferred from the endpoint labels or safety counts.

Finally, the record emphasizes a statistical distinction between observed results and planning scenarios. Sample-size illustrations based on assumptions are not observed power, and assumptions for equal allocation between two arms do not describe the recorded single-group design. Separating those concepts helps prevent planning calculations from being mistaken for evidence about the outcome of this study.

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 important trial-specific limitation in interpreting the posted results is that the registry record does not report the primary response result. Although the endpoint is defined, there is no response count, rate, endpoint denominator, or confidence interval. The reason for termination is also not reported, so the study status cannot explain why the results are incomplete.

Enrollment was 3, and the record describes a single-group design with no comparator. This limits the information available for estimating response in the broader eligible population and means that the design cannot directly estimate a treatment contrast. The enrollment count should not be treated as the number evaluated for every endpoint; the analysis population and missing outcome information are not reported.

The record lists multiple secondary outcomes but does not report their results or a statistical analysis plan. It does not say whether multiplicity was addressed, whether outcome analyses were adjusted, or whether any interim analyses occurred. These matters are not reported in the registry record.

Safety information is also limited. The listed at-risk and affected counts do not include enough context to establish event timing, severity, attribution, overlap between event categories, or the denominator for every reported term. The record does not report deaths in the adverse-event field; this should not be read as confirmation that none occurred. Finally, the study description’s experimental tumor test and eligibility requirements define a selected population, so the registry record does not describe outcomes for people without the required alteration.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Ponatinib for Squamous Cell Lung and Head and Neck Cancers — NCT01761747.
• Registry record last updated 2014-12-23; status last verified 2014-12.
• Results first posted 2014-12-23.
• 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

NCT01761747 is a terminated study of ponatinib in advanced lung and head and neck cancers with FGFR kinase alterations. The registry record lists Phase II and Phase III, a single-group model, no masking, and enrollment of 3. The intervention was ponatinib taken by mouth daily. The recorded start was 2013-01, and primary completion was 2014-06.

The primary endpoint was the response rate, defined as the proportion with investigator-assessed confirmed complete or partial response under RECIST v1.0, with a timeframe of 2 years. The registry record does not report the primary response result or results for the listed secondary outcomes. It lists limited adverse-event counts and “Pancreatits” at 50.0% among top serious adverse terms. The reason for termination, statistical analysis plan, and missing-data handling are not reported in the registry record.