Efficacy, Safety, Tolerability of Gefitinib as 1st Line in Caucasian Patients With EGFR Mutation Positive Advanced NSCLC: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Efficacy, Safety, Tolerability of Gefitinib as 1st Line in Caucasian Patients With EGFR Mutation Positive Advanced NSCLC (NCT01203917), a na phase 4 study. The primary outcome is Objective Response Rate (ORR) (Investigator).

2. Clinical Question

3. Trial Design

This was a Phase 4, open-label, multicentre, single-arm study of gefitinib as first-line treatment. The registry record lists enrollment of 1060 and identifies AstraZeneca as the sponsor. The listed start was 2010-09, primary completion was 2012-08, and the study status is COMPLETED.

Because the study had a single group, participants were not allocated between gefitinib and a control treatment. Allocation is listed as NA, and masking as NONE. There is consequently no randomized, concurrent control group against which to compare the response or safety observations. The design can describe outcomes among participants receiving gefitinib, but it cannot isolate a treatment contrast from differences in patient characteristics, disease course, assessment, or other influences.

The intervention was gefitinib 250 mg, described as a tablet. The study focused on Caucasian patients with EGFR mutation-positive locally advanced or metastatic non-small cell lung cancer. The primary endpoint population is described more narrowly as the Full analysis set of EGFR M+ patients who had taken at least 1 dose. The registry record does not explain the relationship between the total enrollment and the size of this analysis population.

The primary endpoint was investigator-assessed ORR. Secondary outcomes listed in the record were investigator-assessed Disease Control Rate (DCR), investigator-assessed Progression-Free Survival (PFS), and Overall Survival (OS). Although the registry lists seven outcome measures, numerical results for the primary endpoint and the listed secondary outcomes are not reported in the registry record. Details of the study’s statistical analysis plan are also 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: Full analysis set, EGFR M+ patients who had taken at least 1 dose of gefitinib

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.

Population: This is a subset of all the screened patients who are found to be EGFR M+ and who have taken at least one dose of study medication (i.e. EGFR M+ patients are those who have activating sensitising EGFR mutation eligible for the study).

6. Primary Endpoint

The registry lists the primary outcome as Objective Response Rate (ORR) (Investigator), measured over Scans taken at baseline and then follow up assessments taken every 6 weeks until progression, or last evaluable assessment in the absence of progression, assessed up to 23 months.

Objective Response Rate measures the percentage of participants whose cancer met the specified criteria for complete response or partial response. In this study, the assessment was made by the investigator using measurements at the site and RECIST 1.1. A complete response required disappearance of all target and non-target lesions. A partial response required at least 30% decrease in the sum of target-lesion diameters compared with baseline, with no evidence of progression, stable non-target lesions, and no new lesions.

A response counted for the primary endpoint only if repeat imaging confirmed it at least 4 weeks later and there was no evidence of progression between confirmation visits. The stated assessment schedule began with scans at baseline, followed by assessments every 6 weeks until progression or the last evaluable assessment in the absence of progression, assessed up to 23 months.

ORR is used to describe the fraction of an analysis population meeting a defined response criterion. Requiring confirmation helps distinguish a sustained response from a change that is not confirmed on subsequent imaging. The endpoint is an investigator assessment, not an independent central review, according to the registry description. The numerical ORR result, its uncertainty, and the numbers of complete and partial responses are not reported in the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

What does a single-arm response proportion describe?

In general, a response rate is a proportion: the number of people meeting the response definition relative to the number included in the endpoint analysis. It describes the observed frequency in the specified population. The endpoint population and the rule for classifying response are essential to interpreting that proportion. Here, the registry record defines the population as the Full analysis set of EGFR M+ patients who had taken at least 1 dose, and it defines response using investigator assessments under RECIST 1.1 with confirmation by repeat imaging.

A single-arm proportion does not estimate a randomized difference between treatments. Without a concurrent control group, the outcome in the gefitinib group cannot be compared under the same trial conditions with an outcome in a group assigned to another treatment or no treatment. Comparisons with other studies, if made, would be indirect and could reflect differences in populations, outcome assessment, or study conduct. No such comparison is reported in the registry record.

How should precision be assessed?

In general, a confidence interval expresses the statistical uncertainty around an estimate under a stated method. A narrower interval indicates greater precision, while a wider interval indicates less precision. The interval does not remove limitations in the design or guarantee that the estimate applies beyond the studied population. For a response proportion, the estimate and its interval are interpreted together with the numerator, denominator, outcome definition, and analysis population.

The registry record does not report a numerical ORR, response count, endpoint denominator, or confidence interval. Precision therefore cannot be assessed from the registry record. No confidence-interval method or other inferential procedure for the primary outcome is reported in the registry record.

What do endpoint confirmation and assessment timing contribute?

In general, confirming a response requires that the finding persist on a later assessment rather than being counted from a single observation alone. The registry definition required repeat imaging at least 4 weeks later, with no evidence of progression between confirmation visits. The stated schedule was baseline imaging followed by assessments every 6 weeks until progression or the last evaluable assessment in the absence of progression, assessed up to 23 months. These rules specify how response observations were intended to be collected and classified. They do not indicate how missing or unevaluable scans were handled.

The record identifies the investigator as the assessor. In general, an open-label setting means treatment assignment is not masked, and investigator assessment can involve judgment in measurement or classification. The record does not report whether independent review, adjudication, or other procedures were used to check assessments.

What can the safety summaries tell readers?

In general, an adverse-event count describes reported events or participants with events in a defined group; it does not establish that the treatment caused an event. A serious adverse event category is distinct from a measure of treatment benefit. The registry lists serious-event and other-event counts for the Gefitinib 250 mg group and gives percentages for several serious-event terms. The relationship between those safety denominators and the overall enrollment is not explained in the registry record. Event definitions, follow-up duration, and any causal attribution rules are not reported in the registry record.

How do planning illustrations differ from trial results?

In general, a sample-size calculation describes a planning scenario, not an outcome observed in a trial. The registry’s stated planning assumptions describe illustrations computed from the observed effect, using a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation; the effect to detect is the stated fraction of the observed effect. For time-to-event illustrations, the stated quantity is the total number of events; for other illustrations, it is participants per arm. Those assumptions describe a hypothetical two-arm planning exercise, not the design of this single-arm study. The registry record does not report the trial’s own sample-size justification or numerical planning results. Planning illustrations should not be read as observed power or as evidence that a study had a particular probability of detecting an effect.

The registry record does not report the statistical methods used for the trial’s primary or secondary outcome analyses. In particular, it does not state a model, a confidence-interval procedure, or a strategy for handling incomplete outcome data. These omissions mean that an analysis method should not be inferred from the endpoint definition alone.

10. Multiplicity, Missing Data and Analysis Populations

The registry record lists seven outcome measures. It identifies investigator-assessed ORR as the primary outcome and lists investigator-assessed DCR, investigator-assessed PFS, and OS as secondary outcomes. It does not report a testing hierarchy, a multiplicity adjustment, or a rule for interpreting several outcomes together. Whether or how multiplicity was addressed is not reported in the registry record.

Multiplicity matters in general when several outcomes or several comparisons are tested, because interpreting each result separately can increase the chance of a chance-positive finding across a family of tests. This is a general statistical consideration, not a description of a procedure used in this study. No specific procedure can be attributed to the trial from the registry information.

The primary endpoint description identifies the Full analysis set as EGFR M+ patients who had taken at least 1 dose of gefitinib. The registry record does not report the number in that set, how participants without evaluable scans were treated, or whether any imputation or sensitivity analysis was used. It also does not state how missing response assessments, withdrawals, or incomplete follow-up affected the primary analysis. Those rules are important because the classification of participants without adequate outcome data can affect a response proportion.

The registry record lists zero analyses, and numerical results for the primary and secondary outcomes are not reported in the registry record. Thus, the analysis populations beyond the stated Full analysis set definition, missing-data handling, and multiplicity strategy cannot be evaluated from the registry record.

11. 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: vomiting (2.8%), pneumonia (2.8%), cardiac failure (1.9%), diarrhoea (1.9%), pleural effusion (1.9%).

The registry record lists a Gefitinib 250 mg safety group with 107 participants at risk for serious adverse events and 21 affected. It separately lists 107 at risk for other adverse events and 87 affected. These are recorded as participant counts, not estimates of treatment effect. The record does not explain how the safety group relates to the enrollment of 1060 or define the distinction between the serious and other-event categories in further detail.

The most frequent serious-event terms listed are VOMITING and PNEUMONIA, each at 2.8%. CARDIAC FAILURE, DIARRHOEA, PLEURAL EFFUSION, and HYPERTENSION are each listed at 1.9%. These are the percentages stated in the registry record. They should be read as event-term summaries, not as a complete account of all safety outcomes or as proof that gefitinib caused the events. The record does not report the number of deaths in the safety summary; that information is not reported in the registry record.

In general, safety counts require context about definitions, observation time, exposure, and whether participants can appear in more than one event category. The registry record does not provide those details for these summaries. The counts and percentages alone cannot describe the timing, duration, severity beyond the serious classification, or causal attribution of each event.

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

The registry record establishes that this was a Phase 4, open-label, multicentre, single-arm study of first-line gefitinib in Caucasian patients with EGFR mutation-positive locally advanced or metastatic non-small cell lung cancer. It also defines the primary endpoint as investigator-assessed confirmed ORR under RECIST 1.1 in the stated Full analysis set. These design and endpoint details explain what the study set out to characterize.

However, the numerical result for ORR is not reported in the registry record. The response count, endpoint denominator, percentage, and uncertainty are not available there. The listed secondary outcomes—DCR, PFS, and OS—also have no numerical results reported in the registry record. It is therefore not possible to describe the size or precision of the observed efficacy outcomes from the registry information.

Even if a response proportion were available, a single-arm study would describe outcomes observed among participants in that group, rather than an unbiased randomized comparison with another treatment. There is no control arm in this design. The open-label investigator assessment and the absence of reported analysis details also matter when judging how outcomes were classified and analyzed.

The safety summaries report affected-participant counts and selected serious-event percentages, but those summaries do not alone establish causation or provide a full account of safety over time. The relationship between the listed safety population and total enrollment is not explained in the registry record.

Accordingly, the registry information supports understanding the study design, population description, endpoint criteria, and selected safety summaries. It does not support a conclusion about the magnitude of the primary outcome, its precision, comparative benefit, or a causal treatment effect. Such conclusions would require outcome results and analysis details not reported in the registry record.

13. Why This Trial Matters Statistically

This study is statistically informative as an example of the difference between defining an outcome and reporting an outcome. The registry record gives a detailed operational definition for investigator-assessed ORR, including the RECIST 1.1 response criteria, confirmation on repeat imaging, and the intended assessment schedule. Those details make clear what would count as a response. But without the numerical result, endpoint denominator, and uncertainty estimate, readers cannot assess the observed response frequency or its precision.

The single-arm design also illustrates the limits of descriptive evidence. A proportion observed in one treated group can characterize that group, but it does not provide a randomized contrast. Without a comparator, statistical precision around a response proportion would not resolve the separate question of what outcomes would have occurred under another treatment or in the absence of the study intervention.

The record distinguishes an overall enrollment figure from a defined Full analysis set and separate safety counts. Because it does not explain how these populations relate, readers cannot assume they share the same denominator. This underscores why outcome-specific population definitions and participant flow are central to interpretation.

Finally, the listed outcome measures and safety summaries do not substitute for a reported analysis plan. Details about multiplicity, missing data, and analysis methods are not reported in the registry record. Their absence limits reproducibility and makes it difficult to evaluate how the endpoint definitions were translated into final estimates. The record therefore highlights a general principle: a well-described endpoint is useful, but interpretation also depends on transparent results, analysis populations, and uncertainty.

14. 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 numerical results are not reported in the registry record. The primary ORR estimate, its denominator, response counts, and a measure of precision are unavailable. Numerical results for the listed secondary outcomes are also not reported in the registry record, so those outcomes cannot be assessed.

The study has no comparator arm. As a single-group study, it cannot estimate a randomized difference between gefitinib and another treatment. The open-label design and investigator-based response assessment are additional features readers should consider; the registry record does not report independent central review or adjudication procedures.

The registry lists enrollment of 1060, while the safety summary lists 107 at risk for serious events and 107 at risk for other events. The relationship between those counts and the endpoint Full analysis set is not reported in the registry record. The number included in the primary analysis is not reported in the registry record either.

Several analysis details are absent. Missing-data rules, handling of unevaluable scans, analysis methods, multiplicity procedures, and the trial’s sample-size justification are not reported in the registry record. The available safety summary also does not state the observation duration, provide further event definitions, or report the number of deaths. These limits constrain interpretation of efficacy and safety and prevent a fuller assessment of the analyses.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Efficacy, Safety, Tolerability of Gefitinib as 1st Line in Caucasian Patients With EGFR Mutation Positive Advanced NSCLC — NCT01203917.
• Registry record last updated 2017-01-02; status last verified 2016-11.
• Results first posted 2013-10-14.
• 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.

18. Record Summary

The registry record describes NCT01203917, a completed Phase 4, open-label, multicentre, single-arm study sponsored by AstraZeneca. It lists enrollment of 1060, a start of 2010-09, and primary completion in 2012-08. The study evaluated gefitinib 250 mg as first-line treatment in Caucasian patients with EGFR mutation-positive locally advanced or metastatic non-small cell lung cancer.

The primary outcome was investigator-assessed confirmed ORR in the Full analysis set of EGFR M+ patients who had taken at least 1 dose. Secondary outcomes included DCR, PFS, and OS. Numerical efficacy results and analysis details are not reported in the registry record. Selected serious-event counts and percentages are listed, but the relationship between safety denominators and enrollment is not explained.