Open Label Study Of SU011248 In Combination With Trastuzumab For Patients With Metastatic Breast Cancer: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Open Label Study Of SU011248 In Combination With Trastuzumab For Patients With Metastatic Breast Cancer (NCT00243503), a non-randomized phase 2 study. The primary outcome is Percentage of Participants With Overall Confirmed Objective Disease Response.

2. Clinical Question

The study also set out to evaluate safety and tolerability, duration of tumor control and survival, patient-reported outcomes, and pharmacokinetics in combination with trastuzumab. Listed secondary outcomes include duration of response, clinical benefit, progression-free survival, time to progression, overall survival, survival probability at one year, and two EORTC quality-of-life measures. These aims provide context for the trial, but the registry record does not report numerical results for the primary response endpoint or these secondary outcomes.

The design means the central question is descriptive: how often was a confirmed response recorded among the treated participants? Without a control group, the study cannot estimate a comparative treatment effect against another therapy or against no treatment. Its registry entry also does not state a causal question that can be answered by comparing randomized groups. The study is therefore best read as an account of outcomes observed in one treated group, with the endpoint definitions and limitations kept in view.

3. Trial Design

This was a phase 2, open-label, non-randomized, single-group study. Its title describes SU011248 in combination with trastuzumab for metastatic breast cancer; the registry intervention and primary-population description also use the name sunitinib. The condition is listed as breast neoplasms, and the study status is completed. The record lists enrollment as 60.

The study began in 2006-02, with primary completion in 2009-04. The registry gives the primary endpoint timeframe as from the start of treatment through 18 months. It does not report a separate treatment duration or follow-up schedule in the information. The listed intervention is the combination of trastuzumab and SU011248. Dose, administration schedule, and treatment modification rules are not reported in the registry record.

Open-label means that masking was not used, according to the record. The single-group and non-randomized design means participants were not assigned through randomization to a treatment and control arm in this study. Accordingly, there is no internal concurrent control group against which to compare the response percentage or adverse-event frequency. A comparison with outcomes from other populations would require information and assumptions not reported in this record.

The registry describes the primary analysis population as the intent-to-treat population, defined there as all enrolled participants who were treated with the combination. That wording is important: the record does not provide a separate count for participants enrolled but not treated, nor a participant flow account that would clarify exclusions or missing assessments. The design and stated population define who the primary endpoint was intended to describe, but the outcome estimate itself is not reported in the registry record.

The study objectives included overall response, safety and tolerability, duration of tumor control and survival, patient-reported outcomes, and pharmacokinetics. The record names secondary outcomes covering response duration, clinical benefit, progression-free survival, time to progression, overall survival, one-year survival probability, and EORTC QLQ-C30 and QLQ-BR23. Although the registry lists 12 outcome measures, the number of analyses is listed as 0. The statistical analysis plan and any protocol-level rationale for the design or enrollment are not reported in the registry record.

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

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: The intent-to-treat (ITT) population included all enrolled participants who were treated with the combination (trastuzumab and sunitinib).

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 Percentage of Participants With Overall Confirmed Objective Disease Response, measured over From start of treatment through 18 months.

The primary endpoint is the percentage of participants with an overall confirmed objective disease response from treatment start through 18 months. The registry defines an objective response as a confirmed complete response or partial response according to RECIST. A complete response is defined as disappearance of all target and non-target lesions. A partial response is defined using a 30% or greater decrease in the sum of the longest dimensions of target lesions relative to baseline, with non-target disease required to be non-progressive.

This endpoint reduces several tumor-assessment outcomes to a binary classification for each participant: a confirmed response is either recorded or not recorded within the stated timeframe. Reporting the percentage expresses how common that classification was in the treated group. The confirmation requirement and the stated response criteria help specify what counts as an event, rather than treating any change in tumor measurements as a response.

As a general statistical point, a response percentage can be useful for describing activity in a single-group study, while it does not by itself establish that the treatment caused the observed responses. Interpretation also depends on the assessment process, the eligible population, the timeframe, and how participants without an evaluable assessment are handled. The registry record does not report the observed percentage, its confidence interval, or the handling of missing response assessments. Therefore, the endpoint definition is available, but its numerical result and precision cannot be evaluated from the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The primary endpoint is a binary participant-level outcome: a confirmed objective response within the specified timeframe is counted as an event, and absence of a qualifying response is not. The registry reports the endpoint as a percentage of participants, with a 95% confidence interval. The registry record does not include the percentage or confidence interval limits, so the statistical method can be explained, but the estimate itself cannot be interpreted.

What does a response percentage describe?

In general, a percentage for a binary endpoint is a way to summarize the share of an analysis population meeting a prespecified definition. Here, that definition is a confirmed complete or partial response under RECIST, assessed from treatment start through 18 months. The response criteria specify the tumor findings required for classification. A participant-level percentage is not a measure of the amount of tumor change across all participants; it summarizes whether each participant crossed the response threshold and satisfied the confirmation rule.

For a single-group study, the response percentage is descriptive of the treated population included in the analysis. It is not a comparison of two randomized groups. A percentage alone also does not communicate uncertainty: the confidence interval is needed to understand the statistical precision of the estimate. In general, confidence intervals are affected by the amount of available information and the variability inherent in the outcome. No interval bounds are reported for this endpoint, so the degree of precision cannot be judged.

Why does the design matter for interpretation?

Randomization is a method for creating groups that can support a fair comparison, because allocation is not chosen according to participant characteristics or clinical decisions. This study is explicitly listed as non-randomized and single-group, so there is no randomized allocation and no internal control arm. The primary endpoint can still be described as an observed response percentage, but it cannot by itself estimate a contrast between the combination and an alternative. Differences between this group and an external group would be vulnerable to differences in eligibility, assessment, follow-up, and other factors; the registry does not report any such comparison.

The study is open-label, with masking listed as none. In general, knowledge of treatment assignment may influence care, participant reporting, or outcome assessment, depending on the outcome and how it is measured. RECIST-based tumor assessment offers an explicit response framework, but the registry record does not describe independent review, assessment blinding, or other procedures intended to limit assessment bias. These details are not reported in the registry record and should not be assumed.

How should the endpoint definition be read?

The complete-response definition requires disappearance of all target and non-target lesions. The partial-response definition uses a 30% or greater decrease in the sum of the longest dimensions of target lesions relative to baseline, with non-target disease described as non-progressive. Confirmation is part of the endpoint definition. These criteria help determine which participants count as responders, but they do not reveal how many met the criteria. The timeframe also matters: the primary outcome concerns response from treatment start through 18 months, not response at an unspecified point or response after that period.

As a general concept, outcome definitions and observation windows should be read together. A response classification can depend on when assessments occur, whether confirmation is required, and how incomplete follow-up is handled. The registry defines the window and response categories but does not report assessment timing, the number of evaluations, or missing-assessment rules. Those omissions limit interpretation of the measurement process.

What can be concluded from the safety counts?

The registry gives one adverse-event group and records participants affected by serious adverse events and other adverse events. These counts are useful descriptions of the events recorded in that group. The listed serious adverse-event terms have percentages, but the record does not give individual event counts for every term, event timing, recurrent-event counts, or attribution to a particular study treatment. In general, participant counts and event counts are not interchangeable: one participant may experience more than one event. The registry information does not clarify overlap among the listed terms or whether the term percentages use a different event-level convention.

The record lists 25 participants with serious adverse events and 59 with other adverse events among 60 at risk in the corresponding entries. These figures should be read as the registry’s recorded counts, rather than as a complete characterization of clinical severity or causality. The record does not report deaths in the adverse-event entry. It also does not provide an event-by-event account from which to assess duration or resolution.

What statistical details remain unavailable?

The record identifies a 95% confidence interval for the primary endpoint, but does not give its limits or the response estimate. It lists 12 outcome measures and a set of secondary outcomes, but the number of analyses is listed as 0. A detailed statistical analysis plan, including any approach to multiplicity, missing data, or analysis-set deviations, is not reported in the registry record. It is therefore not possible to determine whether analyses were planned or performed beyond the registry information, or to reconstruct the sponsor’s statistical approach.

General statistical interpretation also depends on knowing the analysis population and the denominator used for each outcome. The registry describes the primary population as enrolled participants who were treated with the combination, but does not report a participant flow account or missing-data handling. The enrollment figure alone does not show whether every participant had an evaluable primary endpoint. Consequently, it should not be used to infer a response denominator that the registry does not state.

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("Trastuzumab + Sunitinib")
n      <- c(57)
events <- c(21)
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  Trastuzumab + Sunitinib  57  21  36.8  24.4  50.7  25.5  49.8  25.5  49.9

11. Multiplicity, Missing Data and Analysis Populations

The registry lists several secondary outcomes in addition to the primary response endpoint. These include duration of response, clinical benefit, progression-free survival, time to progression, overall survival, probability of survival at one year, and EORTC QLQ-C30 and QLQ-BR23. It also reports 12 outcome measures overall. The number of analyses is listed as 0, and numerical results for the secondary outcomes are not reported in the registry record.

When a study evaluates multiple outcomes, the chance of finding at least one apparently notable result can be affected by how many comparisons are examined. As a general statistical practice, an analysis plan may specify which outcome is primary, how secondary findings will be interpreted, and whether any adjustment or hierarchy will be used. The registry record does not report a multiplicity strategy or a detailed statistical analysis plan. It is therefore not possible to determine whether or how the listed outcomes were prioritized for inference. No adjustment should be assumed.

The primary population is described as all enrolled participants who were treated with the combination. The registry does not report how many were eligible for each outcome, whether any endpoint assessments were missing, how missing observations were handled, or whether participants were excluded from a particular analysis. Those details matter because percentages and time-to-event summaries depend on which participants and observations contribute to each estimate. Enrollment is not, by itself, evidence that every participant had complete outcome data.

The record names an intent-to-treat population but defines it using treated participants. It does not report an additional analysis population or explain how participants who did not receive treatment, if any, were addressed. The participant flow and missing-data procedures are not reported in the registry record. These gaps prevent assessment of the robustness of the endpoint analyses and make it inappropriate to infer an analysis denominator beyond the stated population description.

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 5% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: thrombocytopenia (5.0%), febrile neutropenia (3.3%), pancreatitis (3.3%), vomiting (3.3%), asthenia (3.3%).

The adverse-event entry lists a single trastuzumab-plus-sunitinib group. It records 60 participants at risk for serious adverse events, with 25 affected, and 60 at risk for other adverse events, with 59 affected. The listed serious adverse-event terms are thrombocytopenia at 5.0%, febrile neutropenia at 3.3%, pancreatitis at 3.3%, vomiting at 3.3%, asthenia at 3.3%, and epistaxis at 3.3%.

These numbers describe what the registry records; they should not be read as a comparison with another treatment because there is no control group. The terms are selected serious adverse-event entries, not a full narrative of every event. The record does not report whether participants experienced more than one listed event, the timing or duration of events, or the basis for attributing an event to treatment. It also does not report deaths in this adverse-event entry.

In general, participant counts and event counts answer different questions: a participant may experience multiple events, while a participant-level count records whether a person was affected. The registry does not supply enough detail to reconstruct event totals or overlap. These safety figures therefore describe the recorded affected participants and selected terms, but do not establish comparative risk or a complete safety profile.

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

The record establishes that a completed phase 2 study evaluated the combination of trastuzumab and SU011248 in metastatic or locally recurrent breast cancer. It defines a primary endpoint based on confirmed complete or partial response under RECIST, assessed from treatment start through 18 months, and identifies a 95% confidence interval as the dispersion measure. It also records selected adverse-event counts for the treated group.

However, the registry record does not report the primary response percentage or its confidence interval. Without those values, the frequency of confirmed response and its precision cannot be described quantitatively. The record also does not report numerical findings for the listed survival, response-duration, clinical-benefit, or patient-reported outcomes. The endpoint definitions and study objectives are not substitutes for outcome estimates.

The non-randomized, single-group design has a further implication. Even if the response estimate were available, it would describe outcomes in the studied group rather than establish a causal difference compared with another treatment. There is no randomized comparator in this study. The design cannot separate the effects of the combination from other possible influences on observed outcomes, and it does not support a like-for-like treatment comparison.

The adverse-event figures provide some information about participants recorded as affected and selected serious-event terms. They do not offer a randomized safety comparison or a complete account of causality, timing, severity beyond the registry classification, or event overlap. The missing details about participant flow and missing outcome data also limit assessment of how completely the analysis population represents those enrolled.

As a result, the registry entry is useful for understanding the question asked, the response definition, the study design, and selected safety counts. It does not support a numerical conclusion about primary efficacy, the precision of the response estimate, or comparative efficacy. It also does not provide the statistical details needed to evaluate multiplicity, missing-data handling, or the full analysis process. These boundaries are important when distinguishing what the record documents from what it cannot establish.

14. Why This Trial Matters Statistically

This study illustrates why an endpoint definition and a numerical result are both necessary for statistical interpretation. The registry specifies what counted as a confirmed objective response and the timeframe in which it was assessed. It also identifies a confidence interval as the measure of uncertainty. But without the response percentage and interval limits, readers cannot judge either the observed response frequency or the precision of the estimate.

The design also makes clear the difference between describing outcomes and estimating a comparative effect. A single-group, non-randomized study can report what happened among participants receiving the combination, but it has no randomized control group for an internal comparison. Statistical methods cannot remove that design limitation after the fact. This is a useful example of why a response percentage, even when available, should not automatically be interpreted as evidence that treatment caused the outcome.

The registry also lists multiple secondary outcomes, including survival, response duration, and quality-of-life measures. Without reported results and a stated multiplicity plan, readers cannot tell how those outcomes were analyzed or how to interpret any individual finding. The record’s lack of reported missing-data procedures and participant flow further underscores that analysis population details are part of the evidence, not administrative extras.

Finally, the safety entry shows why adverse-event summaries need careful reading. Participant counts and selected event terms offer useful descriptive information, but they do not alone describe event overlap, timing, attribution, or comparative risk. The study therefore highlights a broader statistical lesson: results need to be read alongside their definitions, design, uncertainty, analysis population, and reporting limitations.

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 main limitation of the registry entry for interpreting the primary endpoint is that it defines the outcome but does not report the response percentage or the confidence interval. The study timeframe and RECIST response categories are stated, yet the numerical estimate and its precision are unavailable. Numerical results for the named secondary outcomes are also not reported in the registry record.

The single-group, non-randomized design has no concurrent randomized comparator. Any observed outcomes would therefore be descriptive for the treated participants and could not establish a comparative treatment effect from this study alone. The open-label design is another consideration. The record does not describe whether tumor assessments were independently reviewed or blinded, so the safeguards around outcome assessment are not reported in the registry record.

The registry states that the primary population included enrolled participants who were treated with the combination, but does not provide a participant flow account. It does not report whether any participants were untreated, how many had evaluable response assessments, or how missing outcomes were handled. The enrollment figure should not be treated as the endpoint denominator without an explicit reported denominator.

Other details needed to assess the analysis are also absent. The statistical analysis plan, rationale for enrollment, multiplicity approach, and methods for missing data are not reported in the registry record. The adverse-event entry gives affected-participant counts and selected terms, but not event timing, duration, attribution, overlap, or deaths. These limitations do not negate the information that is recorded, but they constrain what can be inferred from it.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Open Label Study Of SU011248 In Combination With Trastuzumab For Patients With Metastatic Breast Cancer — NCT00243503.
• Registry record last updated 2011-07-22; status last verified 2011-07.
• Results first posted 2010-05-19.
• Data retrieved from ClinicalTrials.gov on 2026-11-09.
• Group sizes, means, event counts and sponsor-reported p-values are reproduced as posted. Effect estimates, confidence intervals and p-values not attributed to the sponsor are independently calculated from the posted summary statistics.

19. Record Summary

The registry record describes a completed phase 2, open-label, non-randomized, single-group study of trastuzumab with SU011248 in metastatic or locally recurrent breast cancer. Enrollment was 60. The study began in 2006-02 and primary completion was 2009-04.

The primary endpoint was the percentage of treated participants with confirmed complete or partial objective response from treatment start through 18 months, using RECIST. A 95% confidence interval was specified, but the response estimate and interval are not reported in the registry record. Secondary outcomes include response duration, clinical benefit, progression-free survival, time to progression, overall survival, one-year survival probability, and EORTC quality-of-life measures.

For the listed combination group, the registry records 25 of 60 participants with serious adverse events and 59 of 60 with other adverse events. Selected serious-event terms and percentages are reported. The record does not provide a randomized comparison, numerical primary efficacy result, detailed analysis plan, or missing-data procedures.