Reversing Hormone Resistance in Advanced Breast Cancer With Pazopanib: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Reversing Hormone Resistance in Advanced Breast Cancer With Pazopanib (NCT01466972), a na phase 2 study. The primary outcome is Number of Participants With Clinical Benefit (CB).

2. Clinical Question

The clinical question concerns activity after progression on an NSAI, assessed by a combined endpoint that includes response and stable disease. It is not a question about whether the combination outperformed another treatment: the design has no control arm. The record states that an overall response rate of 20% was considered clinically meaningful, while the primary endpoint is described as clinical benefit. Those are distinct endpoint descriptions in the record, and it does not explain how the stated threshold was related to the clinical-benefit endpoint. The registry record also does not report the rationale for the threshold.

3. Trial Design

This was a phase 2, single-group study of pazopanib in combination with a non-steroidal aromatase inhibitor for advanced breast cancer. The record describes the treatment as non-randomized and open label; masking was none. It lists an enrollment of 30. The study status is completed, with a start date of 2012-04-27 and a primary completion date of 2015-12-07.

Participants had hormone receptor positive advanced breast cancer progressing on the same NSAI hormone therapy. The combination used an NSAI, identified as letrozole or anastrozole, with pazopanib. The record does not report how many participants received each NSAI, whether treatment doses were modified, or how long participants remained on treatment.

The primary endpoint was the number of participants with clinical benefit at 12 weeks. The endpoint definition counted complete response, partial response, or stable disease under RECIST version 1.1. The record says all participants who took at least two weeks of study drug and the NSAI were evaluated for toxicity and efficacy, and identifies 28 patients who met that minimum for the primary endpoint.

Progression-free survival and the number of participants experiencing any treatment-related adverse events are listed as secondary outcomes. The record lists three outcome measures but reports zero analyses. It does not provide a randomized comparison, a control-group outcome, or a statistical analysis plan. The rationale for the enrollment target, eligibility details beyond the stated disease and treatment context, and handling of participants who did not meet the minimum treatment duration 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

Analysis population for the primary outcome, as defined in the registry: Twenty-eight patients met the 2 weeks of treatment minimum needed to be considered evaluable for this endpoint.

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 Number of Participants With Clinical Benefit (CB), measured over 12 weeks.

The primary endpoint is the count of participants with clinical benefit at 12 weeks. Clinical benefit was defined as having a complete response, partial response, or stable disease at that assessment according to RECIST version 1.1. The endpoint therefore includes both tumor shrinkage categories and disease stability; it is broader than an endpoint counting only complete or partial responses.

The registry record identifies 28 patients who met the minimum two weeks of treatment needed to be considered evaluable for this endpoint. It does not report how many of those patients had clinical benefit, nor does it report an accompanying proportion, confidence interval, or test result. The count and its precision therefore cannot be interpreted from the registry record.

In general, a fixed-time clinical-benefit endpoint can describe the fraction of an evaluable group meeting a prespecified disease-status definition at a particular assessment. It gives a direct summary at that time point, but does not by itself describe how long benefit lasts or what happened between assessments. Progression-free survival is listed separately as a secondary outcome. The record does not provide its result or the method used to analyze it.

The record says an overall response rate of 20% was considered clinically meaningful. Because the primary endpoint is clinical benefit, which also includes stable disease, that statement should not be treated as a reported threshold for the primary endpoint without further clarification. That clarification is not reported in the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

What does a count endpoint represent?

The primary outcome is a count of participants meeting the clinical-benefit definition at 12 weeks. In general, a count is the number of people satisfying a defined outcome, while a proportion relates that count to the number assessed. The record supplies the evaluable population size of 28 but not the clinical-benefit count. Without both pieces, no observed proportion can be described. No recalculated estimate is available from the posted information.

In general, binary outcomes such as meeting or not meeting a definition can be analyzed using methods for proportions. The estimated proportion is subject to sampling uncertainty: results in a study group can vary from one sample to another even when the underlying chance of the outcome is unchanged. A confidence interval is commonly used to express this uncertainty. The registry record does not report a confidence interval or the method that would have been used to calculate one.

What does the single-group design allow?

The study is described as single group, non-randomized, and open label. In general, randomization helps create comparable groups for estimating a treatment contrast, while a concurrent control group provides a reference for interpreting outcomes over the same period. Neither is reported for this study. The observed endpoint, if reported, would describe the study group receiving pazopanib with an NSAI; it would not by itself quantify a difference from a control treatment.

Open-label treatment means the study was not masked. In general, knowledge of treatment assignment can affect reporting, care decisions, or outcome assessment, depending on how outcomes are collected. The primary outcome uses RECIST version 1.1, but the record does not describe the assessment procedures or whether assessments were reviewed independently. No further inference about those processes is warranted.

How should planning illustrations be read?

In general, sample-size calculations are planning tools: they describe the number of participants or events that a hypothetical design might need under stated assumptions. The record describes planning illustrations using a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation, with effects expressed as fractions of an observed effect. For time-to-event outcomes, it describes total event counts; for other outcomes, it describes participants per arm.

These are planning assumptions, not the design of this single-group trial. The record does not report a two-arm randomized comparison, and it does not provide the observed primary endpoint effect needed to interpret an illustration based on fractions of that effect. Planning illustrations are not observed power and cannot substitute for the trial’s outcome estimate or uncertainty. No actual participant-per-arm or event-count planning values are reported in the registry record.

What can be said about statistical significance?

In general, a p-value summarizes how compatible data are with a specified statistical model and null hypothesis; it is not a measure of clinical importance and does not give the probability that a treatment works. A significance level is a design convention for interpreting a test, not a result. The planning description includes a two-sided significance level of 0.05, but the registry record lists zero analyses and reports no p-value for the primary endpoint. The planning assumption must not be mistaken for a test result.

For a single-group binary endpoint, an analysis might compare an observed proportion with a prespecified reference value, but the registry record does not report such a test or a statistical plan. The stated 20% threshold refers to overall response rate, whereas the primary endpoint counts clinical benefit including stable disease. The record does not specify a formal null value for the primary endpoint or explain how that threshold was to be applied.

Why is endpoint precision important?

In general, precision depends in part on how many participants contribute outcome information and how the outcome is distributed. A point estimate without an uncertainty measure can appear more definitive than the data warrant. In this record, 28 patients are said to meet the minimum treatment duration for endpoint evaluation, but the number with benefit and the interval around any estimate are not reported. The result’s magnitude and precision cannot be assessed.

Over-dispersion is a general issue for count data when variability exceeds what a simple model expects. The primary endpoint is a participant count with a binary classification, not a rate of recurrent events, and the record reports no dispersion estimate. Over-dispersion should not be presumed to be relevant to this outcome. The registry record also does not describe model-based adjustment, covariates, or subgroup analyses.

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("Pazopanib in Combination With a NSAI")
n      <- c(28)
events <- c(13)
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  Pazopanib in Combination With a NSAI  28  13  46.4  27.5  66.1  29.5  64.2  29.4  64.3

11. Multiplicity, Missing Data and Analysis Populations

The registry record lists three outcome measures, including the 12-week clinical-benefit endpoint, progression-free survival, and treatment-related adverse events. It lists zero analyses. No testing hierarchy, multiplicity adjustment, or plan for selecting among outcomes is reported in the registry record. In general, testing several outcomes can increase the chance of at least one apparently notable result, so prespecified priorities and interpretation rules matter. No such rules can be inferred from this record.

The record identifies 28 patients who met the minimum treatment duration for the primary endpoint and states that all participants taking at least two weeks of study drug and the NSAI were evaluated for toxicity and efficacy. It does not explain the endpoint handling for participants who took less than two weeks, provide a participant flow, or describe imputation or other missing-data procedures. Missing outcome values and their possible influence on an estimate therefore cannot be assessed.

The number enrolled is 30, while the number identified as evaluable for the primary endpoint is 28. These figures refer to different populations in the record and should not be interchanged. No intention-to-treat analysis population, per-protocol definition, or sensitivity analysis is reported. The registry record also does not report whether evaluability was determined before outcome review.

In general, missing data can affect an estimate when participants without recorded outcomes differ systematically from those with outcomes. The direction and extent of any such effect depend on the missingness pattern and assumptions used in analysis. Because the record does not describe the missing outcomes or the analytic approach, no adjustment or sensitivity assessment is available.

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: back pain (3.3%), hypotension (3.3%), thromboembolic event (3.3%), rash maculo-papular (3.3%), fever (3.3%).

The safety record lists 30 participants at risk for the pazopanib-plus-NSAI group. It reports 8 participants affected in the serious adverse-event field, 27 in the other adverse-event field, and 2 deaths. The registry record does not provide event-level timing, participant-level overlap between categories, or details about the deaths. These counts should not be added together, because the record does not establish that the categories are mutually exclusive.

The listed serious-event terms are Back Pain, Hypotension, Thromboembolic event, Rash maculo-papular, Fever, and Aspartate aminotransferase increased, each reported as 3.3%. The record does not provide further detail about severity grades, duration, outcomes, or whether each listed term occurred in a different participant. It also does not establish from these figures alone whether an event was caused by treatment.

In general, an adverse event is an event observed during a study, while attribution to treatment is a separate judgment. The record lists a secondary outcome concerning treatment-related adverse events, but does not report an analysis of that outcome. The counts and terms should therefore be read as the recorded safety information, not as a comparative safety estimate or proof of causation.

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

The registry record describes a completed phase 2 study of pazopanib added to an NSAI in patients with hormone receptor positive advanced breast cancer progressing on the same NSAI therapy. It defines clinical benefit at 12 weeks as complete response, partial response, or stable disease under RECIST version 1.1. It also identifies 28 patients as evaluable after meeting the minimum two-week treatment duration.

The key efficacy result is not reported in the registry record: there is no count of participants with clinical benefit, no estimate of the corresponding proportion, and no uncertainty interval. The available information therefore cannot establish the observed level of clinical benefit or the precision of any estimate. The stated 20% threshold concerns overall response rate and is not itself a study result; the relationship between that threshold and the broader clinical-benefit endpoint is not explained.

Even if a single-group endpoint result were available, it would describe outcomes in the treated study group. Because the record reports no control arm or randomization, it would not establish how outcomes compare with another treatment or what would have occurred without the combination. Differences in patient characteristics, disease course, and other factors could not be separated from treatment effects using a single group alone.

Safety counts are reported, including serious adverse events and deaths, but these do not determine whether treatment caused an event. The record does not give the details needed to interpret the timing, overlap, or circumstances of those events. It also does not report the secondary outcome analyses. Overall, the record supports a careful account of the study design and recorded safety counts, but not a conclusion about comparative efficacy, endpoint success, or causal treatment effects.

14. Why This Trial Matters Statistically

This trial illustrates why an endpoint definition and an endpoint result are different kinds of information. The registry record clearly defines 12-week clinical benefit using complete response, partial response, and stable disease under RECIST version 1.1, and identifies the evaluable population. Yet it does not report the number meeting that definition. Without the outcome count, neither the magnitude of the observed result nor its statistical precision can be assessed.

It also illustrates the interpretive limits of a single-group design. An outcome observed in people receiving a treatment combination does not, on its own, quantify the outcome difference that would have occurred under a different treatment. Randomization and a comparison group are tools for estimating such contrasts; they are not reported in this study. This is particularly important when an endpoint is intended to indicate clinical benefit, because a descriptive count and a comparative treatment effect answer different questions.

Finally, the record distinguishes enrollment from endpoint evaluability: it lists 30 enrolled participants and 28 patients meeting the minimum treatment duration for the primary endpoint. It also reports safety counts but no analyses. These details show why statistical interpretation depends not only on the endpoint definition, but also on who contributed outcome data, what analyses were conducted, and how uncertainty and missing outcomes were handled. Several of those analytic details are not reported 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.

The principal limitation for interpreting efficacy is that the registry record does not report the primary endpoint count. Although it defines clinical benefit and identifies 28 evaluable patients, the result itself, an estimate of its precision, and a statistical test are absent. The listed zero analyses also leave no reported analysis of the primary or secondary outcomes to interpret.

The single-group, non-randomized design does not provide a concurrent control comparison. Any observed outcome would be descriptive of the treated group and could not by itself isolate a treatment effect from other influences. Open-label treatment is reported, but the record does not describe the outcome-assessment procedures or whether assessments were independently reviewed.

The record gives 30 as the enrollment and identifies 28 patients as evaluable for the primary endpoint, but does not provide a detailed participant flow or the endpoint status of those not identified as evaluable. It does not report missing-data methods, an analysis-population definition beyond endpoint evaluability, or sensitivity analyses. These omissions prevent assessment of how exclusions or missing outcomes might affect an endpoint estimate.

The endpoint description also refers to a 20% threshold for overall response rate, while the primary endpoint is clinical benefit and includes stable disease. The registry record does not clarify the connection between the threshold and the primary outcome. Finally, details for progression-free survival and treatment-related adverse events are not reported as analyses, and the safety counts lack timing, overlap, and event-level context. These limitations restrict both efficacy and safety interpretation.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Reversing Hormone Resistance in Advanced Breast Cancer With Pazopanib — NCT01466972.
• Registry record last updated 2020-07-08; status last verified 2020-07.
• Results first posted 2020-06-16.
• 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 NCT01466972, a completed phase 2, open-label, non-randomized single-group study enrolling 30 patients. It evaluated pazopanib added to letrozole or anastrozole in hormone receptor positive advanced breast cancer progressing on the same NSAI therapy.

The primary endpoint was the number of participants with clinical benefit at 12 weeks, defined as complete response, partial response, or stable disease under RECIST version 1.1. The record identifies 28 patients as meeting the minimum treatment duration for endpoint evaluation but does not report the clinical-benefit count or a statistical analysis. Progression-free survival and treatment-related adverse events are listed as secondary outcomes, with zero analyses reported.

Safety entries include 8 participants affected in the serious adverse-event field, 27 in the other adverse-event field, and 2 deaths among 30 at risk. The record provides no randomized comparator and does not report the statistical plan, missing-data methods, or the primary endpoint result.