Ponatinib for Patients Whose Advanced Solid Tumor Cancer Has Activating Mutations Involving the Following Genes: FGFR1, FGFR2, FGFR3, FGFR4, RET, KIT.: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Ponatinib for Patients Whose Advanced Solid Tumor Cancer Has Activating Mutations Involving the Following Genes: FGFR1, FGFR2, FGFR3, FGFR4, RET, KIT. (NCT02272998), a na phase 2 study. The primary outcome is Overall Response, Defined as the Number of Patients Who Achieve Any Response According to Disease Type in the First 6 Courses of Treatment.

2. Clinical Question

In practical terms, this was an investigation of response in a selected, molecularly described population, rather than a randomized comparison of ponatinib with another treatment or with no study treatment. The study summary says that the cancer had spread, had failed previous treatment, and had one of several DNA alterations. The titles name FGFR1, FGFR2, FGFR3, FGFR4, RET, and KIT; the official title also names PDGFRα, FLT3, and ABL1. The detailed eligibility criteria and the way these alterations were distributed across participants are not reported in the registry record.

The clinical question is narrower than whether ponatinib has an effect across all advanced cancers. It concerns whether responses were observed in the enrolled participants, under the study’s response definition and assessment window. Because the primary response result is not reported, the registry record does not establish the observed response frequency or its precision. A single-group study can describe outcomes in its enrolled population, but it cannot separate treatment effects from other explanations as a controlled comparison can.

3. Trial Design

This was a phase II study with a single-group design. The registry reports enrollment of 22 and lists the study as completed. The start date was 2015-02-24, and the primary completion date was 2022-11-17. The sponsor is Sameek Roychowdhuri. Allocation is listed as not applicable, and masking as none. These details describe the registered design; they do not establish how many participants ultimately received treatment or contributed data to each outcome.

The treatment arm received ponatinib hydrochloride by mouth once daily on days 1-28. Courses were to repeat every 28 days unless disease progression or unacceptable toxicity occurred. Laboratory biomarker analysis was also listed. The registry summary describes the target population as patients with metastatic, refractory cancer and one of several genomic alterations. The titles list overlapping but not identical sets of alterations. How the study applied those targets in eligibility decisions is not reported in the registry record.

The primary endpoint was overall response, defined as the number of participants who achieved any response according to disease type in the first 6 courses. The registry gives a timeframe of up to 6 months and describes partial or complete response by RECIST 1.1, assessed with computed tomography scans. It states that the response proportion for the decision rule would use all eligible patients who received any treatment. It also states that 95% binomial confidence intervals would be calculated, assuming responses followed a binomial distribution.

Secondary outcomes listed in the record include adverse events judged possibly, probably, or definitely related to study treatment under National Cancer Institute Common Terminology Criteria for Adverse Events Version 4.0; dose modifications or delays; overall survival; progression-free survival; and clinical benefit rate. The registry identifies 7 outcome measures, but outcome results and detailed analytic methods for these measures are not reported in the registry record. The protocol, sample-size justification, interim analyses, and full statistical analysis plan are also not reported in the registry record. The single-group design means the study does not offer a randomized or masked control comparison.

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 Overall Response, Defined as the Number of Patients Who Achieve Any Response According to Disease Type in the First 6 Courses of Treatment, measured over Up to 6 months.

The primary endpoint counts participants who achieved any response according to disease type during the first 6 courses of treatment. The registry describes response as a partial or complete response under RECIST 1.1, assessed using computed tomography scans. The stated timeframe is up to 6 months. The planned response proportion was to use eligible participants who received any treatment as its denominator.

This endpoint is useful because it defines a clinically interpretable tumor outcome within a specified assessment framework and period. In general, a binary response endpoint classifies each assessed participant according to whether the defined response occurred. The resulting proportion describes how often that outcome was observed in the analyzed population; it does not, by itself, show what would have happened to the same participants under a different treatment. In this single-group study, there is no randomized comparator for that contrast.

The registry describes a planned binomial estimate and 95% binomial confidence intervals. In general, a confidence interval communicates uncertainty about an estimated proportion: a wider interval indicates less precision, while a narrower interval indicates greater precision under the method’s assumptions. The response count, denominator, estimated proportion, and interval are not reported in the registry record. Enrollment of 22 should not be substituted for the endpoint denominator, because the stated denominator is eligible participants who received any treatment and the number meeting that description is not reported.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The primary response analysis was described as a proportion with a binomial model and a 95% binomial confidence interval. The registry says that the response count for the decision rule would be calculated among eligible participants who received any treatment. It defines a response as partial or complete response by RECIST 1.1, assessed using computed tomography scans. The timeframe was the first 6 courses, up to 6 months. The observed response data are not reported in the registry record, so the planned method can be explained but its numerical result cannot be interpreted.

What does a binomial model mean?

In general, a binomial model describes a count of participants with a specified event out of a defined group, when each participant is classified according to whether the event occurred. For this endpoint, the event is the defined tumor response. The corresponding proportion is the event count divided by the relevant analysis population. A binomial model is an assumption about how that count is represented statistically; it does not demonstrate that the assumptions fit the data. The registry’s stated population is eligible participants who received any treatment. The number in that population and the response count are not reported.

In general, a confidence interval expresses uncertainty around an estimate under the selected statistical method. A 95% binomial confidence interval is the interval method identified in the registry for the response proportion. It is not a guarantee that the true response proportion lies in a particular interval, nor does it address every source of uncertainty, such as selection into the study or differences among cancer types. The registry does not report an interval for the primary endpoint. Without its endpoints and the estimate, the precision of the response result cannot be assessed.

Why does the denominator matter?

General statistical interpretation depends on matching the numerator and denominator to the analysis question. The registered primary denominator excludes people who were not eligible or did not receive treatment, according to the stated analysis description. Enrollment is 22, but the record does not state that every enrolled participant was eligible, treated, or evaluated for response. It would therefore be inappropriate to use enrollment as the response denominator without further information. The number assessed, any exclusions, and the handling of participants without evaluable scans are not reported in the registry record.

The response definition also matters. The record specifies partial or complete response according to RECIST 1.1 and computed tomography scans. In general, a consistent assessment rule supports comparability of classifications, while the timing and completeness of assessments affect which outcomes can be counted. The registry does not report scan schedules, independent review procedures, adjudication, or missing-assessment rules. No assumptions about those procedures can be made from the endpoint definition alone.

How should the single-group design be understood?

In general, a single-group study estimates outcomes in the participants who receive the intervention, rather than estimating a randomized contrast between intervention and comparator. This study is listed as single-group, with allocation not applicable and no masking. Its outcome descriptions can therefore be read as observations in the enrolled study population, if results are reported, but not as a controlled comparison. Differences between enrolled participants and a broader population can also limit how widely a single-group result applies. The registry record does not report a comparator or a method for adjusting a treatment effect against an external group.

The record lists ponatinib hydrochloride by mouth once daily on days 1-28, with courses repeating every 28 days in the absence of progression or unacceptable toxicity. In general, treatment interruptions, discontinuations, or changes can affect exposure and interpretation of outcomes. Dose modifications or delays were registered as a tolerability measure, but their results and the analytic handling of treatment changes are not reported. The record also lists laboratory biomarker analysis; it does not report how biomarker findings were incorporated into the primary response analysis.

What can be inferred from the analysis record?

The registry indicates that 7 outcome measures were registered and 0 analyses are listed. This describes what appears in the registry record; it does not establish that no analyses were conducted outside the record. The detailed statistical plan, prespecified subgroup analyses, interim analyses, and sample-size justification are not reported in the registry record. No unreported analysis method or design rationale should be inferred.

General statistical practice distinguishes planning assumptions from observed results. The record’s planning description refers to a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation for sample-size illustrations. Those are assumptions for planning illustrations, not evidence of the actual single-group design or a calculation of observed power. The registered study itself has no comparator arm. The illustration outputs and a study-specific sample-size justification are not reported in the registry record. Any sample-size illustration should be understood as a hypothetical planning calculation, not as a measure of the probability that this completed study detected an effect.

More broadly, statistical methods answer defined questions under specified assumptions. The response endpoint and binomial interval describe a planned approach, but the absence of reported results prevents assessment of the estimate, its precision, and the model’s practical adequacy. Important details concerning missing assessments, analysis populations, outcome review, and multiplicity are likewise not reported 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("Participants With Genomic Alterations in FGFR", "Participants With Genomic Alterations in Rare Geno")
n      <- c(17, 5)
events <- c(1, 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  Participants With Genomic Alterations in FGFR  17  1  5.9  0.1  28.7  1.0  27.0  1.4  27.3
ARM  Participants With Genomic Alterations in Rare Geno  5  0  0.0  0.0  52.2  0.0  43.4  0.4  45.9

11. Multiplicity, Missing Data and Analysis Populations

The registry identifies 7 outcome measures. The listed secondary outcomes include treatment-related adverse events, dose modifications or delays, overall survival, progression-free survival, and clinical benefit rate, in addition to the primary response endpoint. The record does not report a multiplicity strategy, such as a method for controlling the chance of false-positive findings across multiple outcomes or analyses. In general, when several outcomes are examined, the chance of at least one apparently notable result can increase unless the analysis plan addresses that issue. This is a general statistical concern, not a claim that any particular finding in this study is false.

The registry states that the response proportion would be based on eligible participants who received any treatment. Other analysis populations, including the populations used for the secondary outcomes, are not reported in the registry record. The number of participants eligible, treated, assessed, or included in each analysis is not reported. Those populations should not be assumed to match the overall enrollment of 22.

Missing-data methods are not reported in the registry record. In general, missing outcome assessments can affect an estimated proportion if participants with unavailable assessments differ from those with observed outcomes. The registry does not specify how missing scans, withdrawal, treatment discontinuation, or incomplete follow-up would be handled for response or other endpoints.

The registry record does not report interim analyses, subgroup analysis plans, or a detailed statistical analysis plan. It also does not report a sample-size justification. These absences limit assessment of how outcomes and analyses were prespecified and how multiplicity or missing data were addressed. They do not establish that such procedures were absent outside 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: abdominal pain (4.5%), anorexia (4.5%), ascites (4.5%), thromboembolic event (4.5%).

The safety figures describe participants in the treatment group. The registry reports 3 affected by serious adverse events among 22 at risk, and 22 affected by other adverse events among 22 at risk. It lists abdominal pain, anorexia, ascites, and thromboembolic event among the serious terms, each at 4.5%. The record also reports 16 deaths. These are separate descriptive safety counts; they should not be treated as evidence about the primary response endpoint.

The secondary safety outcome is defined as the percentage of participants with adverse events classified as possibly, probably, or definitely related to study treatment under National Cancer Institute Common Terminology Criteria for Adverse Events Version 4.0. The registry does not report the result for that defined treatment-related outcome. The serious-event terms and the affected-participant counts alone do not indicate whether each event was considered related to treatment, how severe each event was, or when it occurred. The relationship of the reported deaths to treatment is also not stated.

In general, safety counts need context about event definitions, observation time, attribution, and whether the figures refer to participants or event episodes. The registry labels these as participants affected and identifies participants at risk, but does not give event timing or duration. The counts should be read as the safety information recorded, not as a complete causal assessment.

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

The registry describes a completed phase II, single-group study of ponatinib hydrochloride in advanced cancers with selected genomic alterations. It provides a primary response definition and the method planned for estimating a response proportion, but the observed response count, proportion, and confidence interval are not reported in the registry record. The primary efficacy result therefore cannot be characterized from this record.

Even if a response estimate were available, a single-group study would describe outcomes among the treated participants rather than establish a randomized difference from another treatment. In general, causal comparisons require a credible basis for distinguishing the effects of treatment from other factors. This registry lists no comparator, no allocation, and no masking. Its design cannot answer a controlled comparative question.

The record reports safety counts, including 3 participants affected by serious adverse events among 22 at risk, 22 affected by other adverse events among 22 at risk, and 16 deaths. It also lists four serious-event terms at 4.5% each. These registry entries describe the posted safety information but do not establish event attribution, timing, or cause. The defined secondary outcome for treatment-related adverse events and the other registered secondary outcome results are not reported in the registry record.

The intended population is selected by advanced cancer and genomic alterations. The titles name several potential targets, but participant counts by tumor type or alteration are not reported. In general, results from a mixed population may not apply equally to each disease or molecular subgroup, especially when subgroup-specific estimates are unavailable. Here, no subgroup response results are reported.

Accordingly, the record supports an account of the study’s design, planned response method, and posted safety counts. It does not supply the response result, a comparative treatment effect, or enough detail to assess survival outcomes, subgroup outcomes, or all safety questions. These limits concern what can be interpreted from the registry record and should not be replaced with assumptions about unreported results.

14. Why This Trial Matters Statistically

Statistically, the study is notable for asking a response question in a population selected by genomic alterations while using a single-group design. The endpoint is clearly framed as a count of participants with partial or complete response during the first 6 courses, with the response proportion and 95% binomial confidence interval planned for eligible participants who received any treatment. That framing identifies the intended outcome and analysis population, even though the resulting estimate is not reported in the registry record.

The design also illustrates the distinction between describing an outcome and estimating a comparative treatment effect. A single-group proportion can summarize what was observed in participants receiving the regimen, but without a control group it cannot by itself show how outcomes compare with another treatment or with an alternative course. This matters when interpreting claims based on response frequency, because the design does not isolate treatment effects from other influences.

The registry’s molecular focus raises a further statistical issue: broad eligibility across multiple genomic targets and cancer types can encompass clinically different groups. In general, an overall estimate may obscure variation among subgroups. Participant distributions and subgroup-specific response results are not reported, so the degree of such variation cannot be assessed.

Finally, the record separates a planned endpoint method from reported results. It includes a binomial confidence-interval plan and safety counts, yet does not report the primary response estimate or results for the listed secondary outcomes. The study is therefore a useful example of why interpretation requires both a clear endpoint definition and the actual numerator, denominator, and uncertainty estimate. Without the primary outcome data, the central response question remains unanswered in the registry record.

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.

A key limitation for interpretation is that the primary response result is not reported in the registry record. The endpoint definition and planned confidence-interval method are available, but the observed response count, denominator, proportion, and interval are not. Enrollment of 22 does not establish the number eligible, treated, or assessed for response, and those counts are not reported.

The single-group design has no concurrent comparator. Allocation is listed as not applicable and masking as none, so the registry does not support a randomized comparison. The study summary describes metastatic, refractory cancers with selected genomic alterations, while the titles list multiple targets. The number of participants by cancer type or alteration, and subgroup-specific outcomes, are not reported. This limits assessment of how an overall result might vary across the enrolled population.

Other limitations arise from the detail available in the registry. The sample-size justification, detailed statistical analysis plan, interim analyses, multiplicity approach, missing-data rules, and analysis populations beyond the stated primary denominator are not reported in the registry record. The record does not specify how incomplete response assessments were handled or provide results for the registered survival, clinical benefit, and tolerability outcomes.

The safety information is also limited in detail. Counts and serious-event terms are reported, but event timing, attribution, and causes of death are not. These gaps do not prove that the study lacked further analyses or information; they mean those details cannot be assessed from the registry record. No result should be inferred from the absence of a posted outcome.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Ponatinib for Patients Whose Advanced Solid Tumor Cancer Has Activating Mutations Involving the Following Genes: FGFR1, FGFR2, FGFR3, FGFR4, RET, KIT. — NCT02272998.
• Registry record last updated 2025-03-24; status last verified 2025-03.
• Results first posted 2025-03-24.
• 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

NCT02272998 is a completed phase II, single-group study of ponatinib hydrochloride in advanced cancers with selected genomic alterations. The registry reports enrollment of 22, a start date of 2015-02-24, and a primary completion date of 2022-11-17. Treatment was scheduled by mouth once daily on days 1-28, with courses repeating every 28 days in the absence of progression or unacceptable toxicity.

The primary endpoint was overall response in the first 6 courses, defined as partial or complete response by RECIST 1.1 using computed tomography scans. A binomial response proportion and 95% confidence interval were planned. The primary response result is not reported in the registry record. Safety counts include 3 participants affected by serious adverse events among 22 at risk, 22 affected by other adverse events among 22 at risk, and 16 deaths. The record does not report the results for the other registered outcomes or the detailed statistical plan.