Pazopanib in Patients With Relapsed or Refractory Small Cell Lung Cancer: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Pazopanib in Patients With Relapsed or Refractory Small Cell Lung Cancer (NCT01253369), a na phase 2 study. The primary outcome is 8-Week Progression-Free Rate.

2. Clinical Question

3. Trial Design

This was a phase II, single-group study of pazopanib in patients with relapsed or refractory SCLC. The registry lists an enrollment of 33 and identifies Dana-Farber Cancer Institute as the sponsor. The study status is completed. Its recorded start was 2010-06, and primary completion was 2012-09.

There was no randomized allocation, and masking was listed as none. A single-group design can describe outcomes observed among participants receiving the study treatment, but it does not create a concurrent control group. Differences from outcomes in other settings cannot be attributed to treatment by a direct randomized comparison within this study.

Pazopanib was given orally at 800 mg once per day in 28 day cycles (+/- 3 days). Treatment continued as long as patients were receiving clinical benefit; the criteria used to determine that benefit are not reported in the registry record. The recorded treatment duration was a median of 3 cycles, with a range of 1-20. This describes treatment duration among the reported study participants; it does not establish why treatment ended for any particular participant.

The primary endpoint was the 8-week progression-free rate, defined using complete response, partial response, or stable disease at the first assessment. The secondary outcome listed was Objective Response Rate. The registry record lists 2 outcome measures but no analysis records. It does not report a protocol-level statistical plan, sample-size justification, interim-analysis plan, or details of how the secondary outcome was analyzed. These omissions prevent a fuller reconstruction of the planned and conducted statistical analyses.

The study population for the response endpoint was not necessarily all 33 enrolled participants. The record defines evaluable patients as those with measurable disease at baseline, at least 1 cycle of therapy, and a disease re-evaluation. The number meeting those conditions is not reported in the registry record. This distinction matters because an enrolled-participant count alone does not specify the denominator used for a response estimate.

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 analysis dataset is comprised of evaluable patients. Patients who had measurable disease at baseline, received at least 1 cycle of therapy and had their disease re-evaluated were considered evaluable for response.

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 8-Week Progression-Free Rate, measured over For this endpoint, disease was evaluated radiologically at baseline and week 8 on treatment; Treatment continued until disease progression or unacceptable toxicity. Treatment duration was a median of 3 cycles range (1-20)..

The primary endpoint, the 8-week progression-free rate, describes the proportion of evaluable patients whose disease was classified as complete response, partial response, or stable disease by the first radiological assessment at 8 weeks. It combines response and disease stability into a binary outcome: each evaluable patient either meets that endpoint definition or does not. The endpoint is not the same as objective response rate, because stable disease is included in the progression-free definition but is not itself a complete or partial response.

The registry describes assessment at baseline and week 8 using RECIST 1.1. For target lesions, complete response means disappearance of all target lesions. Partial response requires at least a 30% decrease in the sum of longest diameters, relative to the baseline sum. Stable disease means neither enough decrease for partial response nor enough increase for progressive disease. Progressive disease requires at least a 20% increase from the smallest sum on study, with at least 5 mm of absolute increase. Response needed confirmation within 4 weeks. For non-target lesions, progression-free status requires no new lesions and no unequivocal progression of existing non-target lesions.

General statistical context: a fixed-time endpoint gives a status at a specified assessment, rather than describing the full timing of progression over follow-up. It can be clinically interpretable as a proportion, but its meaning depends on the assessment schedule, endpoint rules, and analysis population. The registry record does not report the observed 8-week rate, its 80% confidence interval, or the evaluable denominator. Therefore, the endpoint definition is available, but the numerical result and its precision are not reported in the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The statistical information in the registry record is incomplete for reconstructing the endpoint analysis. It identifies a binary percentage outcome, describes the endpoint criteria, and specifies that an 80% confidence interval is the dispersion measure. However, the observed estimate, confidence limits, analysis denominator, and analysis records are not reported in the registry record. The statistical concepts below explain how such an endpoint is generally interpreted, without assuming which calculation was used in this study.

What does a binary percentage represent?

General statistical context: a binary outcome places each participant into one of two categories for the endpoint, such as meeting or not meeting a prespecified definition. The percentage is the number of participants meeting the definition relative to the participants included in the analysis. The denominator is essential: the same count can yield different percentages under different analysis populations. Here, the record says that response-evaluable patients had measurable disease at baseline, received at least 1 cycle, and underwent disease re-evaluation, but it does not report how many participants satisfied those conditions or the resulting endpoint percentage.

For this endpoint, the success category is defined broadly as complete response, partial response, or stable disease by the 8-week assessment. This makes the outcome a classification at a specified time. It does not mean that all participants in the success category had tumor shrinkage, since stable disease is included. Nor does the classification by itself describe the duration of disease control after the assessment.

What does the confidence interval communicate?

General statistical context: a confidence interval is an uncertainty summary around an estimated quantity. Its width depends on factors such as the amount of information in the analysis and the variability of the observed data, as well as the method used to construct the interval. A narrower interval indicates greater precision under that method; a wider interval indicates less precision. The registry identifies an 80% confidence interval for the primary endpoint, but does not report its limits or the interval-construction method. The estimate and its precision therefore cannot be assessed from the registry record.

A confidence interval is not a guarantee that an estimate is close to a particular value, and it does not remove design limitations. In particular, an interval around a single-group proportion would quantify uncertainty for that proportion under its analysis assumptions; it would not create a control group or correct for the absence of randomization.

How do RECIST criteria define endpoint status?

The outcome uses RECIST 1.1 classifications based on radiological assessment. For target lesions, complete response is disappearance of all target lesions. Partial response is a decrease of at least 30% in the sum of longest diameters compared with the baseline sum. Stable disease is neither a sufficient decrease for partial response nor a sufficient increase for progressive disease. Progressive disease is an increase of at least 20% from the smallest sum on study, together with at least 5 mm of absolute increase. Response needed confirmation within 4 weeks. For non-target lesions, progression-free status requires no new lesions and no unequivocal progression on existing non-target lesions.

These rules make the endpoint dependent on assessment timing and classification. The record states that disease was evaluated radiologically at baseline and week 8 for this endpoint. It does not provide details about any deviations from that schedule, how missing or indeterminate assessments were handled, or whether assessments underwent independent review. Such details are not reported in the registry record and should not be inferred.

Why does the analysis population matter?

General statistical context: an analysis population defines which participants contribute to an estimate. The recorded evaluability definition requires measurable disease at baseline, at least 1 cycle of therapy, and disease re-evaluation. Participants who did not meet one or more conditions may not contribute under that definition, but the record does not report their number or the handling of their data. It also does not identify a separate intention-to-treat analysis for this endpoint.

When participants are excluded from a response analysis because they lack an assessment, the resulting estimate can describe the assessed group rather than everyone enrolled. The implications depend on why assessments are missing and how missing outcomes relate to disease status. Those reasons and the missing-data method are not reported in the registry record. Thus, the analysis-population rule is known in general terms, but the extent and potential influence of exclusions cannot be evaluated.

What can a single-group analysis establish?

General statistical context: a single-group proportion describes the outcome frequency observed under the study conditions. Without a randomized comparator, it does not directly estimate a contrast between treatment strategies. In a randomized comparison, the groups can support a between-group treatment estimate under the design and analysis assumptions; in a single-group study, there is no such concurrent contrast. Historical comparisons, if made elsewhere, would require information about comparability and are not reported in the registry record.

The registry lists no analysis records. It does not report a statistical model, hypothesis test, covariate adjustment, confidence-interval construction method, or interim-analysis procedure. These methods should not be presumed. General explanations of proportions and intervals cannot identify which specific analytic choices were made.

What do planning calculations mean?

General statistical context: a sample-size planning illustration estimates the number of participants that might be needed under stated assumptions, including a target effect and a significance level. Such an illustration is not an observed trial result and is not observed power. A calculation based on a fraction of an observed effect is conditional on that effect and on the assumptions used for the calculation. It does not show that the study had a particular probability of detecting an effect after the data were collected.

The registry record does not report the trial's own sample-size justification or statistical plan. Any planning illustration should therefore be read as a separate hypothetical calculation, not as evidence about what the investigators planned or what the study demonstrated. The missing observed endpoint estimate also prevents evaluation of how any such illustration relates to the primary outcome.

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")
n      <- c(30)
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  Pazopanib  30  0  0.0  0.0  11.6  0.0  11.4  0.1  11.2

11. Multiplicity, Missing Data and Analysis Populations

The registry lists the 8-week progression-free rate as the primary endpoint and Objective Response Rate as a secondary outcome. It also lists 2 outcome measures, but no analysis records. The registry record does not report whether formal hypothesis tests were conducted, whether outcomes were analyzed in a prespecified order, or whether any adjustment for multiple comparisons was planned or used. Multiplicity methods should not be inferred from the presence of more than one outcome.

General statistical context: when several outcomes or comparisons are tested, the chance of at least one apparently notable result can increase if each is assessed separately without accounting for the multiplicity. Adjustment methods and hierarchical testing strategies can address this issue, but their use depends on a prespecified analysis plan. Because the relevant plan is not reported in the registry record, the handling of multiplicity cannot be assessed.

The response-analysis population is described as evaluable patients: those with measurable disease at baseline, at least 1 cycle of therapy, and disease re-evaluation. The number of participants meeting that definition is not reported in the registry record. The record does not report how missing assessments, unevaluable patients, or incomplete outcome data were handled, nor does it describe sensitivity analyses for missing data.

These omissions matter because a percentage depends on its denominator and on the rules for classifying participants without an assessment. General statistical context: excluding participants with missing outcomes can yield an estimate for those assessed, while counting missing outcomes as failures or using another method targets a different quantity. No such handling rule should be assumed. The record also does not report whether an intention-to-treat population or another analysis population was used for the primary endpoint. Consequently, neither the impact of missingness nor the exact analysis population can be determined from the registry record.

12. Safety Results

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

Other (non-serious) adverse events

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

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: ventricular arrhythmia (15.2%), cardiac disorders - other, specify (12.1%), hepatobiliary disorders - other, specify (9.1%), nausea (6.1%), fatigue (6.1%).

The registry lists 33 participants at risk in the pazopanib group for both serious and other adverse events. It records 12 participants affected by serious adverse events and 26 affected by other adverse events. These are participant counts, not event totals, and the registry record does not give the definitions used for these categories or clarify whether participants could contribute to both categories.

The listed serious adverse-event terms and percentages are ventricular arrhythmia, 15.2%; cardiac disorders - Other, specify, 12.1%; hepatobiliary disorders - Other, specify, 9.1%; nausea, 6.1%; fatigue, 6.1%; and lipase increased, 6.1%. These are registry-listed terms and percentages. The record does not specify in this listing whether the terms are mutually exclusive, whether a participant could have more than one listed event, or the detailed event-collection and attribution rules. They should not be added together to form a total.

General statistical context: adverse-event counts describe observations in the study population and are not, by themselves, comparative estimates of excess risk. In a single-group study, there is no randomized control group for a direct safety comparison. The death count is not reported in the registry record. The listed counts also do not establish causality, severity beyond the serious-event categorization, or how risks compare across treatments.

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

The record establishes that a completed phase II, single-group study evaluated pazopanib in patients with relapsed or refractory SCLC. It provides the primary endpoint definition, the timing and RECIST 1.1 basis of the assessment, the response-evaluability rule, and selected safety counts and terms. These details describe what the study was designed to assess and some of the recorded safety information.

The primary endpoint result itself is not reported in the registry record. The observed 8-week progression-free rate, its 80% confidence interval, and the evaluable denominator are absent. Therefore, the primary endpoint's magnitude and precision cannot be described. The secondary outcome, Objective Response Rate, is listed, but its numerical result is also not reported in the registry record. A completed status does not fill this gap.

The endpoint definition combines complete response, partial response, and stable disease at 8 weeks. It should not be treated as a measure of tumor shrinkage alone, nor as a description of how long any classification persisted. The recorded assessment is tied to a particular time point and to the stated criteria. The record does not report later endpoint values or the full course of disease assessments.

The design does not include a randomized comparator. Thus, observations in the pazopanib group cannot be interpreted as a randomized treatment difference. The study record does not establish what would have happened to a comparable group receiving another treatment or no study treatment. Any cross-study comparison would require careful consideration of differences in patients, assessment, and study conduct, and such a comparison is not reported.

The adverse-event figures describe affected participants and selected terms within the study group. They do not by themselves establish that pazopanib caused the events or show how the frequency compares with another treatment. The absence of a reported death count, event definitions, and detailed event attribution further limits safety interpretation.

In general, a registry record can support a clear account of design and outcome definitions even when numerical results or analysis details are missing. In this case, the missing primary estimate, interval, denominator, and analysis methods mean that the record does not support a numerical conclusion about the primary endpoint or a comparative efficacy claim. No treatment recommendation follows from these registry entries.

14. Why This Trial Matters Statistically

This study illustrates why endpoint definitions and analysis populations need to be read together. The primary outcome is called an 8-week progression-free rate, but its operational definition includes complete response, partial response, and stable disease at the first assessment. Those categories have distinct meanings. A participant classified as having stable disease contributes to the endpoint, even though that category does not require the decrease in lesion size specified for partial response.

The endpoint also depends on the assessment schedule and RECIST 1.1 rules. A status at week 8 is a fixed-time outcome, not a full description of the timing or duration of disease control. The record specifies radiological evaluation at baseline and week 8 for this endpoint, but does not provide the observed result or describe handling of absent assessments. The evaluability definition further makes the analysis denominator important: enrollment was 33, while the number meeting the response-analysis criteria is not reported in the registry record.

The design offers a useful statistical contrast with randomized trials. This was a single-group study with no randomized allocation or masking. It can characterize outcomes and adverse-event reports within the enrolled study group, but it does not estimate a randomized between-group difference. That distinction is central when interpreting any observed percentage or safety count.

The registry also demonstrates the limits of interpreting an incomplete results record. A named endpoint and a stated confidence-interval level do not reveal the actual estimate or its precision. Likewise, a completed status and a listed secondary outcome do not supply the missing numerical results. Transparent reporting of denominators, estimates, uncertainty, analysis populations, missing-data rules, and multiplicity methods is needed to assess results fully. Where those details are absent, the scientifically appropriate interpretation is limited to what the record states, rather than filling gaps with assumptions.

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.

Several limitations specific to this study record constrain interpretation. The most consequential is that the registry does not report the observed primary endpoint value, its 80% confidence interval, or the number of evaluable participants. Although enrollment was 33, the response population was defined by measurable baseline disease, receipt of at least 1 cycle, and disease re-evaluation. The record does not give the count meeting those criteria, so the endpoint denominator cannot be verified.

The single-group design provides no randomized comparator. Differences between the observed outcomes and results from other groups or studies cannot be interpreted as a treatment contrast without additional evidence about comparability. Masking was listed as none, and no allocation to multiple groups was recorded.

The endpoint is assessed at 8 weeks and includes stable disease as well as complete and partial response. It therefore does not summarize only objective tumor response or the duration of disease control. The record gives the classification criteria but does not report whether independent review was used, how missing or indeterminate assessments were treated, or whether assessment deviations occurred.

The registry lists Objective Response Rate as a secondary outcome, but its result is not reported. It lists 2 outcome measures and no analysis records; the statistical plan, sample-size justification, interim-analysis procedures, multiplicity handling, and missing-data methods are not reported in the registry record. The listed adverse-event information also lacks detailed definitions and attribution rules, and the death count is not reported. These gaps prevent a complete assessment of efficacy, precision, analysis choices, and comparative safety.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Pazopanib in Patients With Relapsed or Refractory Small Cell Lung Cancer — NCT01253369.
• Registry record last updated 2019-04-23; status last verified 2019-04.
• Results first posted 2016-01-12.
• 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

This completed phase II study enrolled 33 participants with relapsed or refractory SCLC and evaluated pazopanib in a single group. Pazopanib was given orally at 800 mg once per day in 28 day cycles (+/- 3 days), with treatment continuing while participants were receiving clinical benefit. The recorded treatment duration was a median of 3 cycles, range 1-20.

The primary endpoint was the 8-week progression-free rate, defined by complete response, partial response, or stable disease under RECIST 1.1. The response-analysis population was defined as evaluable patients with measurable disease at baseline, at least 1 cycle of therapy, and disease re-evaluation. The registry record does not report the observed primary estimate, its 80% confidence interval, or the evaluable denominator. Objective Response Rate was listed as a secondary outcome, but its numerical result is not reported in the registry record.

The record lists 12 participants affected by serious adverse events and 26 by other adverse events, with 33 at risk in each category. No randomized comparator or analysis records are listed. Statistical-plan details, missing-data handling, and multiplicity procedures are not reported in the registry record.