Phase II Dasatinib Study in Advanced Breast Cancer: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Phase II Dasatinib Study in Advanced Breast Cancer (NCT00546104), a non-randomized phase 2 study. The primary outcome is Estimation of the Proportion of Progression-free Patients at 16 Wks..

2. Clinical Question

The primary endpoint concerns progression-free status at a specified time, rather than tumor response alone. The registry defines progression using RECIST v1.0: a 20% increase in the sum of the longest diameters of target lesions, a measurable increase in a non-target lesion, the appearance of new lesions, or a similar definition as appropriate. The endpoint description also includes death from any cause as an event, with the first documented progression or death determining the event time.

The registry record identifies 31 patients and describes several participant dispositions around the 16-week assessment. It does not report the estimated proportion progression-free at that time, the confidence interval, or a complete account of how all dispositions entered the final calculation. As a result, the clinical question is clear, but its numerical answer cannot be read from the registry record.

3. Trial Design

This was a phase II trial of dasatinib in women with stage IV or inoperable stage III advanced breast cancer. The registry lists Duke University as the sponsor, records enrollment of 31, and gives the study status as completed. The recorded start was 2007-10 and the primary completion was 2011-05.

The design is described as non-randomized, with a single group and no masking. Participants received dasatinib; the registry describes the dose as 50- 100 mg PO BID. No parallel control arm is recorded. This design can describe outcomes among treated participants, but it does not provide a concurrent group receiving another treatment or no study treatment for a direct comparison.

The primary outcome was estimation of the proportion of participants who were progression-free at 16 weeks. The registry also lists secondary aims concerning response by RECIST criteria, SRC dysregulation at specified assessments, the relationship between SRC findings and response or time to progression, and osteoclastic bone resorption. These aims indicate that the record covered more than the primary endpoint, but detailed outcome estimates for these aims are not reported in the registry record.

Because the study had a single group, results must be interpreted as observations within this enrolled cohort. The registry record does not describe a randomized allocation procedure, a masked assessment process, or a comparator-based analysis. Further details about eligibility criteria, dose modification rules, treatment duration, or the study protocol are not reported in the registry record. The label phase II does not, on its own, establish what sample-size justification or decision criteria were used.

4. Participant Flow and Accounting

The registry reports how participants moved through each stage of the study. All counts below are exactly as posted; missing counts are not inferred from other stages.

Before assignment: Meds which inhibit platelet function/coagulation,potent inhibitors of cytochrome CYP3A, or meds that prolong the QT interval during study require a 7 day wash-out.IV bisphosphonates must be held for 2 wks before/6 wks after trial tx. Subjects must be 3 wks since prior to therapy, 2 wks since surgical bx and 3 wks since major surgery.

Overall Study

Analysis population for the primary outcome, as defined in the registry: 31 patients on this trial, 1 patient was found to have disease progression at 16-weeks, 16 patients had disease progression prior to 16 weeks, 8 patients were taken off-treatment due to toxicity, and 6 patients voluntarily withdrew from treatment. These latter two groups of patients were censored in the analysis of Progression Free Survival.

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 Estimation of the Proportion of Progression-free Patients at 16 Wks., measured over 16 weeks.

The primary endpoint is the proportion of participants progression-free at 16 weeks. It asks whether progression or death had been documented by the specified time after the first day of study-related dasatinib treatment. The registry's event definition treats the first documented progression or death from any cause as the event, whichever came first.

Progression is defined using RECIST v1.0. The listed criteria include a 20% increase in the sum of the longest diameters of target lesions, measurable growth in a non-target lesion, or the appearance of new lesions, with a similar definition allowed as appropriate. This makes the endpoint dependent on disease assessments and the registry's progression rules, not simply on whether a participant remained on treatment.

As a general statistical concept, a fixed-time progression-free proportion gives a snapshot of the fraction of a study population not known to have experienced the endpoint by a chosen time. It differs from a response rate, which concerns whether tumors meet response criteria, and from a time-to-event summary, which uses the timing of events across follow-up. Participants whose event status is not known through the assessment time require a stated rule for censoring or other handling. The registry record says some participants were censored but does not provide a complete account of the calculation or a numerical estimate and confidence interval for the primary endpoint.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

What does a fixed-time proportion describe?

As a general statistical explanation, a proportion at a fixed time classifies participants according to whether an event has occurred by that time. In this trial, the event is progression or death, and the specified assessment point is 16 weeks. The measure is intended to describe the share of the study population who have not had a recorded event by that point, subject to the handling of participants whose event status is incomplete.

This measure differs from a tumor response measure. A response analysis asks whether participants meet response criteria, while the primary endpoint asks whether progression or death has occurred by a designated time. A participant could therefore be progression-free without meeting a response definition. The registry separately lists a secondary aim to measure response by RECIST criteria.

Why does the progression definition matter?

The registry defines progression using RECIST v1.0 criteria, including a 20% increase in the sum of the longest diameters of target lesions, measurable increase in a non-target lesion, or new lesions. The specific rule matters because the endpoint depends on how assessments are classified. The registry also allows a similar definition as appropriate. Detailed assessment schedules, review procedures, and adjudication methods are not reported in the registry record.

As a general principle, the event definition should be applied consistently across participants. Unmasked assessment can be relevant to interpretation because knowledge of treatment may influence some aspects of measurement or reporting. The registry records no masking, but does not describe whether any independent review or other safeguards were used. Such procedures are not reported in the registry record.

What does censoring mean for this endpoint?

In general, censoring records that an event time is not observed in full. For a fixed-time estimate, the analysis needs to establish whether a participant's available follow-up is sufficient to classify their status at the target time or whether their incomplete follow-up must be accounted for through a time-to-event method. The registry description says that participants taken off treatment due to toxicity and participants who voluntarily withdrew were censored. It does not provide the complete sentence describing this handling, the censoring dates, or the method used to obtain the reported proportion.

Stopping treatment and stopping follow-up are not necessarily the same. As a general concept, a participant may discontinue study treatment but still be followed for progression or death. Whether follow-up continued after treatment discontinuation is not reported in the registry record. The record also does not provide a detailed account of missing assessments, deaths contributing to the primary endpoint, or the follow-up status of every participant.

How should a confidence interval be read?

As a general statistical explanation, a confidence interval expresses uncertainty around an estimated quantity under the assumptions of the analysis. A wider interval indicates less precision, while a narrower interval indicates greater precision. The interval does not guarantee that the true value lies within its particular limits, and it does not resolve possible bias from incomplete follow-up, endpoint assessment, or study design.

The primary outcome title specifies a 95% confidence interval, but neither the estimate nor the interval limits are reported in the registry record. Without those values, the size and precision of the primary result cannot be evaluated. The registry record also does not identify the exact statistical method used to calculate the interval.

What can a single-group study estimate?

As a general statistical concept, a single-group study can estimate an outcome within the group that was observed. It cannot directly estimate a treatment contrast against a concurrent control group. Non-randomized allocation also means there is no randomized comparison in this record. The registry explicitly notes that the arms are not a like-for-like control comparison; the study is in fact recorded as a single-group design.

The registry lists planning illustrations based on an observed effect, using a two-sided significance level of 0.05, equal allocation between two hypothetical arms, and a normal approximation. It describes those calculations as planning illustrations rather than the trial's own design. Since this trial has a single group and no randomized comparison, such assumptions do not convert its observed results into a controlled comparison. The numerical illustrations are not reported in the registry record, and the trial's original sample-size justification is not reported in the registry record.

As a general concept, planning calculations depend on assumptions about the effect to detect, variability, allocation, and statistical method. A planning illustration is not observed power and does not show that an analysis had a particular probability of finding a result after the data were collected. The registry does not report the protocol's sample-size rationale or the assumptions used in the original design.

What do the additional aims imply?

The registry lists secondary aims involving response, SRC dysregulation, time to progression, and osteoclastic bone resorption. As a general statistical matter, examining multiple outcomes or relationships raises the possibility of chance findings across analyses. Whether and how to account for that depends on the analysis plan and the role assigned to each outcome. A multiplicity strategy is not reported in the registry record, and the record does not establish which secondary analyses were confirmatory or exploratory.

The registry states that there were two analyses, but detailed model specifications, covariate adjustments, subgroup rules, and analysis populations are not reported in the registry record. The presence of an endpoint definition and an interval label is not enough to reconstruct the statistical analysis. These limitations leave the numerical primary result and the analytic choices behind it unverified from the registry record alone.

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("Dasatinib")
n      <- c(31)
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  Dasatinib  31  0  0.0  0.0  11.2  0.0  11.0  0.1  10.9

11. Multiplicity, Missing Data and Analysis Populations

The registry lists a primary endpoint and several secondary aims, including response by RECIST criteria, SRC dysregulation over time, relationships between SRC findings and response or time to progression, and osteoclastic bone resorption. Multiple outcomes and analyses can increase the chance of at least one apparently notable result arising by chance. As a general statistical principle, multiplicity methods or a clear distinction between confirmatory and exploratory aims can help readers interpret that risk. A multiplicity adjustment or prespecified hierarchy is not reported in the registry record.

The registry describes 8 participants as taken off-treatment due to toxicity and 6 as voluntarily withdrawing, and says these groups were censored. It also reports progression before 16 weeks for 16 patients and progression at 16-weeks for 1 patient. The complete censoring description, follow-up status for every participant, handling of missing assessments, and any sensitivity analysis are not reported in the registry record. No death count for the primary endpoint is reported in the registry record.

The analysis population is not fully specified. The record does not state whether the primary analysis included all enrolled patients under a named analysis-population rule or whether exclusions were made. It also does not report the complete statistical analysis plan, interim analyses, or a sample-size justification. These omissions limit assessment of whether all participants and outcomes were handled according to prespecified rules. The posted description of selected dispositions does not substitute for a full account of missing-data methods or analysis populations.

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 1% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: pleural effusion (9.7%), pain (6.5%), dyspnea (6.5%), pain, back (3.2%), pain, extrimity limb (3.2%).

For the dasatinib group, the registry reports 31 participants at risk for serious adverse events and 10 affected. For other adverse events, it reports 31 at risk and 30 affected. These are separate safety summaries and should not be read as efficacy results. The record does not provide a death count in the adverse event summary; deaths are not reported in the registry record.

The listed serious adverse event terms and percentages are Pleural Effusion, 9.7%; Pain, 6.5%; Dyspnea, 6.5%; Pain, back, 3.2%; Pain, extrimity limb, 3.2%; and Anorexia, 3.2%. These are registry-listed terms, not a substitute for a complete account of event severity, timing, duration, or outcome. The registry record does not give additional context for interpreting the term-level percentages.

As a general statistical point, adverse event summaries describe events observed and reported under the study's recording rules. They do not establish that an event was caused by treatment, and a participant-level count does not describe the full clinical course. The record's figures should therefore be read as safety reporting in this single group, not as a comparison with another treatment.

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

The posted record establishes that this was a completed, non-randomized, single-group phase II study of dasatinib in advanced breast cancer. Its primary question concerned progression-free status at 16 weeks, using progression criteria based on RECIST v1.0 and including death from any cause in the event definition. The registry also supplies selected disposition information and serious adverse event figures.

The record does not report the primary endpoint estimate or its 95% confidence interval. It therefore does not give the numerical proportion progression-free at 16 weeks or the precision of that estimate. The disposition counts alone do not fill this gap, particularly because some participants are described as censored and the full analysis method is not reported.

As a general statistical principle, an observed outcome in a single group describes that group, but cannot by itself show what would have happened under a different treatment or no study treatment. Without a concurrent comparator and random allocation, differences attributable to treatment cannot be separated from other influences through a randomized contrast. The record also does not report enough analysis detail to assess all sources of uncertainty, including missing follow-up and assessment procedures.

The serious adverse event summary reports 10 affected participants among 31 at risk, while the other adverse event summary reports 30 among 31 at risk. The listed serious event terms provide further descriptions, but do not establish causation or allow a comparative safety assessment. No death count is reported in the adverse event summary.

These findings should be understood as registry information about the design, endpoint, selected dispositions, and safety reporting. They do not support a conclusion about treatment benefit or lack of benefit. The principal result needed to quantify the primary endpoint is not reported in the registry record, and several protocol and analysis details are also absent.

14. Why This Trial Matters Statistically

This trial illustrates why the design and the endpoint must be read together. A fixed-time progression-free proportion has an intuitive clinical interpretation, but it depends on a clear event definition, adequate follow-up, and transparent handling of participants whose status is not observed through the target time. The registry gives a RECIST-based progression definition and identifies groups described as censored, while leaving the full censoring account and numerical endpoint estimate unreported.

The single-group, non-randomized design is also central to interpretation. Such a study can document outcomes among treated participants, but it does not create a randomized control comparison. That distinction matters when describing what an observed proportion can establish. The registry's planning illustrations use equal allocation between hypothetical arms, yet those assumptions do not make this trial a two-arm comparison.

The record also shows how a trial can have several scientific aims alongside a primary endpoint. Response, SRC dysregulation, time to progression, and bone resorption appear among the secondary aims. Without a reported multiplicity strategy or a clear classification of analyses, readers cannot determine how the range of aims was reflected in statistical interpretation.

Finally, a named endpoint and a confidence-interval label do not replace the actual estimate, interval limits, or analysis specification. When these are absent, readers can identify the intended question and some relevant participant dispositions but cannot judge the primary result's magnitude or precision. This is a practical lesson in registry reading: design, outcome definition, missing-data handling, and reported numerical results all contribute to the strength of a statistical interpretation.

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 principal limitation of the registry record for interpreting efficacy is that the primary estimate and its 95% confidence interval are not reported. Although the outcome title specifies progression-free status at 16 weeks and the record gives selected progression and withdrawal counts, it does not report the final proportion or the method used to calculate it.

The description of censoring is incomplete. It identifies 8 participants taken off-treatment due to toxicity and 6 who voluntarily withdrew as censored, but the record does not give censoring times, confirm whether follow-up continued after treatment stopped, or explain the full analysis procedure. The primary endpoint includes death from any cause, but a death count for that endpoint is not reported in the registry record.

The design is non-randomized and single-group, with no comparator. This limits the conclusions to outcomes observed in the enrolled group and prevents a direct randomized treatment comparison. The registry records no masking; details of progression assessment, independent review, and other safeguards are not reported in the registry record.

Further limitations include the absence of a reported original sample-size justification, complete statistical analysis plan, multiplicity strategy, interim-analysis details, and fully specified analysis population. The registry lists secondary aims but does not provide their detailed results in the information recorded for this analysis. These gaps prevent a full assessment of precision, selection, missing-data assumptions, and the extent to which analyses followed prespecified plans.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Phase II Dasatinib Study in Advanced Breast Cancer — NCT00546104.
• Registry record last updated 2013-07-17; status last verified 2013-07.
• Results first posted 2013-07-17.
• 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

NCT00546104 is a completed phase II, non-randomized, single-group study sponsored by Duke University. It enrolled 31 patients with advanced breast cancer and evaluated dasatinib, recorded as 50- 100 mg PO BID. The recorded start was 2007-10 and primary completion was 2011-05.

The primary endpoint was the proportion progression-free at 16 weeks, with progression defined using RECIST v1.0 criteria and death from any cause included in the event definition. The registry describes progression, treatment discontinuation, and withdrawal dispositions, but does not report the primary estimate or its confidence interval. It also reports serious and other adverse event counts and selected serious event terms. Detailed censoring methods, the analysis population, multiplicity handling, and the original sample-size justification are not reported in the registry record.