AZD0530 to Treat Recurrent Stage IIIB/IV NSCLC Previously Treated With Combination Chemotherapy: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for AZD0530 to Treat Recurrent Stage IIIB/IV NSCLC Previously Treated With Combination Chemotherapy (NCT00638937), a na phase 2 study. The primary outcome is Rate of Disease Control (Freedom From Disease Progression).

2. Clinical Question

The study asks whether patients with recurrent stage IIIB or stage IV non-small cell lung cancer, previously treated with platinum-based combination chemotherapy, experience disease control during treatment with saracatinib. Disease control was defined using objective response or stable disease, with the response assessed under RECIST 1.0. The primary endpoint required the response or stable disease to persist for at least 4 cycles (16 weeks) of therapy, with the stated timeframe of 112 days.

The question is descriptive for the treated group, rather than a comparison of saracatinib with another treatment or with a control group. The registry record lists enrollment of 37, but does not report the number included in the primary endpoint analysis or a numerical primary endpoint result. It therefore does not show how many participants met the disease-control definition or how uncertain an estimated rate might be.

3. Trial Design

The registry identifies this as a phase 2 study with a single-group model. Allocation is listed as not applicable, and masking is listed as none. The record describes one treatment group receiving saracatinib; it does not identify a placebo group or another active treatment group. This design can describe outcomes among participants receiving the study treatment, but it does not provide a concurrent comparison for separating treatment effects from other explanations for observed outcomes.

The population was patients with recurrent, advanced non-small cell lung cancer who had previously received combination chemotherapy that included cisplatin or carboplatin. The conditions listed include recurrent non-small cell lung cancer and stage IIIB and stage IV non-small cell lung cancer. The treatment description specifies saracatinib by mouth, 175 mg once daily on days 1-28, with courses repeated every 28 days in the absence of unacceptable toxicity or disease progression. The registry lists enrollment of 37.

The primary outcome was the rate of disease control, defined as complete response, partial response, or stable disease, with disease control required to last at least 4 cycles (16 weeks) of therapy. The stated outcome timeframe is 112 days. Secondary outcomes include objective response rate, stable disease rate, duration of response or stable disease, median progression-free survival, progression-free survival, median overall survival, and overall survival. Although these outcomes are named in the record, numerical results for them are not reported in the registry record.

The study is marked completed. Its recorded start was 2008-02 and its primary completion was 2013-06. The registry names the National Cancer Institute as sponsor. The record does not report a randomized comparison, a control group, or masking, so the design should be read as an account of outcomes in a treated group rather than as a controlled estimate of comparative benefit.

4. Participant Flow and Accounting

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

Overall Study

5. Baseline Characteristics

The table reproduces the baseline characteristics posted in the registry, which describe the participants analysed at baseline and help show whether the randomized groups were comparable.

6. Primary Endpoint

The registry lists the primary outcome as Rate of Disease Control (Freedom From Disease Progression), measured over 112 days.

The primary endpoint is the rate of disease control, described as freedom from disease progression. It combines complete response, partial response, and stable disease under RECIST 1.0, with the response or stable disease required to persist for at least 4 cycles (16 weeks) of therapy. The registry gives 112 days as the timeframe. A complete response is described as disappearance of all target lesions, while a partial response is described as at least 30% decrease in the sum of the longest diameters of target lesions.

This endpoint combines tumor shrinkage with a period of stable disease. In general, a composite endpoint can summarize more than one clinically relevant type of outcome, but its interpretation depends on the components and the duration requirement. Here, a participant could meet the definition through complete response, partial response, or stable disease; the record does not report the component-specific results. Consequently, even a reported combined rate would not by itself show how much each response category contributed.

The endpoint is intended to characterize disease control over a specified treatment period, not to establish a comparative treatment effect. The registry describes standard descriptive statistics and says that 95% confidence intervals would be provided for estimates where possible. However, a numerical disease-control result and its confidence interval are not reported in the registry record. The endpoint definition is available, but its observed rate and precision cannot be assessed from this record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The methods description in the registry record is limited. It states that standard descriptive statistics, such as the mean, median, range, and proportion, would be used to summarize the patient sample and estimate parameters of interest. It also states that 95% confidence intervals would be provided for estimates where possible. Detailed analysis procedures, model specifications, and numerical analysis results are not reported in the registry record.

What does a disease-control rate represent?

A rate is a proportion: it relates the number of participants meeting a specified outcome definition to an analysis population. For this study, the definition combines complete response, partial response, and stable disease lasting at least 4 cycles (16 weeks). To interpret a rate, readers need both the outcome definition and the population used as its denominator. The record gives the definition and enrollment of 37, but does not report the denominator used for the primary analysis or the number meeting the endpoint. A rate cannot be reconstructed from the definition or enrollment alone.

The endpoint is composite because participants can qualify through different response categories. In general, a combined measure can be useful when its components each represent an outcome of interest, but the total can conceal differences among those components. A combined disease-control result would not tell readers whether participants had complete response, partial response, or stable disease unless those component results were reported separately. The registry lists objective response rate and stable disease rate as secondary outcomes, but does not report their numerical results.

What does a confidence interval add?

In general, a confidence interval describes the sampling uncertainty around an estimated quantity, given the method and its assumptions. A narrower interval indicates greater statistical precision than a wider interval, but neither width nor coverage can be judged without the actual estimate and interval. The registry says 95% confidence intervals would be provided where possible; it does not report the interval for the primary endpoint. The intended use of an interval is not evidence that a result was precise, nor does an interval address all possible biases in a study.

For a single-group study, a confidence interval around a disease-control rate would describe uncertainty about that group’s rate under the analysis assumptions. It would not estimate a contrast with an untreated or differently treated group. General statistical uncertainty and the limitations of the design are separate issues: an estimate can have a calculable interval while still lacking a causal comparison.

What can descriptive statistics tell readers?

Descriptive statistics characterize the observed data. A mean or median summarizes a distribution in different ways; a range describes its observed extremes; and a proportion describes the share meeting a definition. These summaries do not, by themselves, explain why an outcome occurred. Which summary is useful depends on the type and distribution of the data. The registry does not report the actual summary values for the primary outcome or the listed secondary outcomes.

The study lists time-to-event outcomes, including progression-free survival and overall survival, as secondary measures. In general, time-to-event analysis concerns both the time until an event and whether that event was observed during follow-up. Participants whose event time is not observed may contribute incomplete follow-up information, depending on the method. The record does not report the analysis method, censoring rules, follow-up details, or numerical survival estimates. It is therefore not possible to assess how those issues were handled.

How should the planning illustrations be read?

The planning illustrations are statistical illustrations, not observed power. Their stated assumptions are a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation, with the effect to detect expressed as a fraction of the observed effect. The record also distinguishes illustrations for time-to-event outcomes, which use a total event count, from other illustrations, which use participants per arm. These assumptions do not describe the trial’s design: the study itself is single-group, with no randomized comparison. The registry record does not report that these planning assumptions were the study’s design rationale, and the illustrations should not be interpreted as actual trial results or as evidence that the study had a particular probability of detecting an effect.

Over-dispersion is a general statistical concern when outcome variability exceeds what a chosen model assumes. If it is not accounted for, standard errors and confidence intervals can be misleading. The registry record does not identify a model for the primary endpoint or report whether over-dispersion was assessed. It would be inappropriate to assume that any particular model or correction was used.

Likewise, the record does not report an interim-analysis plan, stopping boundaries, covariate adjustment, or a prespecified statistical analysis plan. Those details should not be inferred from the phase designation, outcome list, or descriptive-statistics statement. In the absence of a numerical result and fuller methods, the defensible interpretation is restricted to what the registry explicitly states: a single-group design, the outcome definitions, and an intended descriptive approach with confidence intervals where possible.

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("Treatment (Saracatinib)")
n      <- c(37)
events <- c(4)
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  Treatment (Saracatinib)  37  4  10.8  3.0  25.4  4.3  24.7  4.4  24.8

11. Multiplicity, Missing Data and Analysis Populations

The registry lists a primary disease-control outcome and secondary outcomes covering response, stable disease, duration of disease control, progression-free survival, and overall survival. When several outcomes are assessed, general statistical interpretation must consider multiplicity: the chance of at least one apparently unusual result can increase when many hypotheses are tested. The registry record does not report a multiplicity adjustment, a hierarchy among secondary outcomes, or a plan for interpreting multiple tests. It also reports no analyses or numerical results for these outcomes. No claim about statistical significance across outcomes can therefore be assessed from this record.

Missing-data handling is not reported in the registry record. The record does not specify how participants without an evaluable response assessment, incomplete follow-up, treatment discontinuation, or missing outcome measurements were handled. These details matter because the analyzed population and the treatment of missing observations can affect a reported estimate. The enrollment figure of 37 should not be assumed to be the denominator for every outcome.

The primary outcome description gives no population field, and the registry record does not define an intention-to-treat, per-protocol, safety, or other analysis population. It does not report how many participants entered each analysis. Consequently, readers cannot determine whether the primary endpoint used all enrolled participants or a subset, or how the analysis set differed across outcomes.

In general, multiplicity procedures, missing-data rules, and analysis-population definitions help clarify how estimates and tests should be interpreted. Their absence from the registry record does not establish that such procedures were not used in study conduct; it means they are not reported in 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 5% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: death nos (5.4%), hypoxia (5.4%), thromboembolic event (5.4%), fever (5.4%), lower gastrointestinal hemorrhage (2.7%).

The registry lists 37 at risk and 10 affected in the serious-adverse-event group for saracatinib. It also lists serious-event terms with percentages: Death NOS, hypoxia, thromboembolic event, and fever are each reported as 5.4%; lower gastrointestinal hemorrhage and increased INR are each reported as 2.7%. The record does not provide a count alongside each term in this listing, so those percentages should be read as reported rather than converted into counts.

The separate other-adverse-event group lists 37 at risk and 37 affected. These group-level figures do not explain the severity, duration, timing, or relationship to treatment of each event. A participant may have more than one event; the registry listing does not establish a one-to-one correspondence between affected participants and event terms.

In general, an adverse event recorded during a study is not necessarily caused by the study treatment. The registry record does not report causal attribution for the listed serious-event terms. Nor does the listing alone provide a comparative safety estimate, because the study has no concurrent control group. These entries describe the safety information recorded, not a causal conclusion.

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

The record establishes that a phase 2, single-group study of saracatinib was conducted in patients with recurrent, advanced non-small cell lung cancer previously treated with platinum-based combination chemotherapy. It specifies the treatment regimen and a primary endpoint based on complete response, partial response, or stable disease sustained for at least 4 cycles (16 weeks). It also identifies secondary outcomes and reports that the study is completed.

Those details do not establish the observed disease-control rate. The numerical primary result, its confidence interval, and the numerical secondary results are not reported in the registry record. The record therefore does not show how many participants met the primary endpoint, how precisely any endpoint was estimated, or what the progression-free or overall survival results were. The outcome definitions cannot stand in for outcome results.

The design also limits what a result could mean. In general, a single-group study can describe outcomes among people who received a treatment, but it cannot provide a direct randomized comparison against another treatment or no treatment. Even if a group’s outcome rate were available, the design would not by itself show that the treatment caused that rate. Other influences on outcomes cannot be separated from treatment effects through a concurrent control comparison in this study.

The safety entries have a similarly bounded interpretation. They report affected participants and listed serious-event terms, but do not establish that saracatinib caused those events or show how safety compares with another treatment. The registry record also does not report the analysis populations or missing-data procedures needed to assess how incomplete observations affected endpoint estimates.

In general, a statistical result can describe an observed outcome and its uncertainty without answering every causal or clinical question. Here, the record supplies design and endpoint definitions but no numerical efficacy results. It therefore supports neither a conclusion that saracatinib did nor did not improve outcomes. It supports a narrower reading: the study intended to measure disease control and other outcomes in a treated group, while the posted registry record does not report those outcome estimates.

14. Why This Trial Matters Statistically

This trial illustrates why a clearly defined endpoint and a reported endpoint result are different things. The registry describes disease control in terms of response categories, RECIST 1.0, a duration requirement of at least 4 cycles (16 weeks), and a timeframe of 112 days. These details help readers understand what the intended measure means. Without the observed rate, however, the endpoint definition cannot answer how often disease control occurred in the study.

It also illustrates the interpretive boundary of a single-group design. Such a study can describe outcomes among participants who receive the treatment, but a treatment effect is fundamentally comparative: it concerns how outcomes differ from what would occur under an alternative. Without a concurrent comparator, differences attributable to treatment cannot be isolated by the study design alone. This is a design limitation, not a question resolved by a larger or smaller confidence interval.

The record also names multiple secondary outcomes and states an intention to use descriptive statistics and confidence intervals where possible. That information shows why analysis methods matter: outcome definitions, uncertainty, analysis populations, missing-data rules, and multiplicity plans all influence what readers can conclude. Several of those details and all numerical endpoint results are not reported in the registry record.

Finally, the safety listing demonstrates the distinction between observing an event and attributing it to treatment. A registry can report affected participants and event terms without establishing causation or a comparative risk. Reading those entries with appropriate limits is part of sound 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.

Several limitations are specific to the information recorded for this study. The design is single-group, with allocation listed as not applicable and masking listed as none. There is no concurrent control group for a like-for-like comparison, so the record cannot provide a randomized estimate of relative treatment effect. The enrollment figure is 37, but the registry does not state the primary endpoint analysis denominator or the number of participants evaluable for each outcome.

The primary endpoint combines complete response, partial response, and stable disease sustained for at least 4 cycles (16 weeks). The record does not report a numerical result for the combined endpoint or separate numerical results for its components. The endpoint description gives 112 days as the timeframe. How outcome assessments were scheduled, how missing assessments were handled, and how the timeframe related to participant-level follow-up are not reported in the registry record.

Although the record lists response and survival outcomes, it does not report their numerical results, confidence intervals, or detailed analytic methods. It does not report the analysis populations, censoring rules for time-to-event outcomes, multiplicity procedures, or a statistical analysis plan. The registry’s statement that confidence intervals would be provided where possible does not establish that every interval was calculated or that any particular result was precise.

The safety listing reports affected participants and serious-event terms but does not report causal attribution for those terms or provide a concurrent safety comparison. The registry record also does not report an interim-analysis plan or a sample-size justification for the actual single-group design. Planning illustrations with equal allocation between two arms should not be mistaken for the design of this study or its observed power.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: AZD0530 to Treat Recurrent Stage IIIB/IV NSCLC Previously Treated With Combination Chemotherapy — NCT00638937.
• Registry record last updated 2018-08-29; status last verified 2018-07.
• Results first posted 2015-07-14.
• 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, single-group study sponsored by the National Cancer Institute. It lists enrollment of 37 and evaluates saracatinib in recurrent stage IIIB or stage IV non-small cell lung cancer after platinum-based combination chemotherapy. The recorded start was 2008-02, and primary completion was 2013-06.

Saracatinib was given by mouth at 175 mg once daily on days 1-28, with courses repeating every 28 days unless unacceptable toxicity or disease progression occurred. The primary endpoint was disease control, defined as complete response, partial response, or stable disease lasting at least 4 cycles (16 weeks), with a stated timeframe of 112 days.

The registry record does not report numerical primary or secondary outcome results, detailed analysis populations, or missing-data methods. It lists serious-adverse-event information, including 10 affected among 37 at risk, and serious-event terms with percentages. The single-group design does not provide a concurrent treatment comparison.