A Study of EGF816 and Gefitinib in TKI-naïve EGFR-mutant Non-Small Cell Lung Cancer: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for A Study of EGF816 and Gefitinib in TKI-naïve EGFR-mutant Non-Small Cell Lung Cancer (NCT03292133), a na phase 2 study. The primary outcome is 9 Months Progression Free Rate.

2. Clinical Question

The study asked whether a combination of EGF816 and gefitinib could be evaluated in people with TKI-naïve EGFR-mutant non-small cell lung cancer. Its primary endpoint was the progression-free rate at 9 months: the percentage of participants free from objective disease progression or death at that time after treatment started.

The registry also lists overall response rate, median overall survival, median progression-free survival, and treatment-related adverse events as secondary outcomes. These outcomes could describe tumor response, time-to-event experience, and safety, but their results are not reported in the registry record. The record therefore identifies the clinical question and the intended combination, but does not provide an outcome estimate that answers whether the primary endpoint was met.

3. Trial Design

This was a phase 2, single-group study sponsored by Massachusetts General Hospital. The registry lists enrollment of 11 and describes one treatment group, EGF816 plus gefitinib. There was no separate control arm, and the allocation field is listed as NA. The study was not masked. These design features mean that the registry record does not describe a randomized, blinded comparison between treatment strategies.

The arm description states that all patients would receive gefitinib orally once daily and that EGF816 would also be administered orally once daily. Participants were requested to maintain a medication diary documenting each dose. The record does not report whether all enrolled participants started both drugs, how long treatment continued, or what treatment changes were permitted.

The study start date is 2017-10-31, and the listed primary completion date is 2021-12-31. Its current status is TERMINATED. The reason for termination and the timing of that decision are not reported in the registry record. Termination by itself does not establish why the study stopped or what outcomes were observed.

The primary endpoint was a 9-month progression-free rate, defined by freedom from objective disease progression or death at 9 months after treatment started. Progression was evaluated using RECIST 1.1. Secondary outcomes listed in the registry include overall response rate, median overall survival, median progression-free survival, and treatment-related adverse events. The record does not describe the statistical analysis plan, the planned analysis populations, or how follow-up and endpoint status were handled when data were unavailable.

Because this is a single-group study, any outcome observed in the group would not by itself distinguish a treatment effect from other explanations, such as the course of disease or differences in participant characteristics. The registry record does not supply a comparator-based 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

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 9 Months Progression Free Rate, measured over 9 months.

The primary endpoint is the 9-month progression-free rate. It is a binary endpoint at a specified follow-up time: each participant is classified according to whether they are free from objective disease progression or death at 9 months after treatment begins. The endpoint description defines the reported measure as a percentage of participants meeting that condition.

Progression is assessed using Response Evaluation Criteria in Solid Tumors, version 1.1. The registry defines progressive disease as at least a 20% increase in the sum of target-lesion diameters, relative to the smallest sum on study, together with an absolute increase of at least 5 mm. The appearance of one or more new lesions also counts as progression. These criteria make the progression component depend on specified imaging-based rules rather than an informal judgment alone.

A fixed-time progression-free rate can provide an interpretable snapshot of the proportion meeting the endpoint at a clinically specified follow-up point. Unlike a median time-to-event measure, it focuses on status at the chosen time. Its interpretation depends on complete and appropriately handled follow-up, including how deaths, progression assessments, and missing assessments are classified. Those analysis details are not reported in the registry record.

The record does not report the observed 9-month rate, its denominator, or a confidence interval. The endpoint definition is therefore available, but its numerical result and precision cannot be assessed from the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry identifies the primary outcome as a participant count for a binary endpoint: progression-free status at 9 months. A binary endpoint assigns each participant to one of two categories for the specified assessment, based on whether the endpoint condition is met. The planned summary is a percentage, but the registry record does not report the numerator or denominator used to calculate it, or the resulting percentage.

What does a fixed-time rate describe?

A fixed-time rate describes the proportion of the analyzed group that meets a defined condition at a specified follow-up point. Here, the condition is being free of objective progression or death at 9 months after treatment starts. It is distinct from a time-to-event summary, which uses information about how long participants remain free of an event. Although median progression-free survival is listed as a secondary outcome, no result for that measure is reported.

For a fixed-time rate to be interpretable, the analysis needs a clear rule for deciding which participants are eligible for the denominator and how incomplete follow-up is treated. For example, participants who discontinue treatment or do not have an assessment at the target time may still have relevant follow-up information, but the analysis must specify how such cases are classified. The registry record does not report those rules, the analysis population, or the amount of missing endpoint information.

How is progression defined?

The endpoint uses RECIST 1.1 to assess objective progression. The registry description defines progressive disease using changes in the sum of target-lesion diameters and also treats the appearance of one or more new lesions as progression. A standardized criterion is useful because it sets a common measurement rule for classifying progression. Interpretation still depends on how assessments were scheduled, reviewed, and handled when a scan or measurement was unavailable; those details are not reported in the registry record.

What would a confidence interval add?

In general, a confidence interval expresses the uncertainty around an estimated quantity under a statistical model and its assumptions. For a binary rate, the interval would help readers judge how compatible the observed data are with a range of underlying rates. It does not remove uncertainty or address bias caused by the study design, missing data, or measurement practices. No confidence interval for the primary endpoint is reported in the registry record, so the precision of any rate cannot be assessed.

Why does the design affect interpretation?

The study is listed as single-group, with no separate comparator, and the allocation field is NA. A within-group proportion can describe the participants observed, but it cannot by itself estimate a difference between the combination and another strategy. Randomized comparisons are designed to support such contrasts by creating groups whose allocation is determined by chance. This study's registry description does not include that kind of comparison. The record also says masking was none, so it does not describe blinded assessment; how the endpoint assessments were conducted is not reported.

These design features matter for interpretation, not because a particular result can be assumed, but because they define what conclusions an observed estimate could support. The registry record gives no adjusted or comparative estimate and lists no analyses. It does not report a statistical model for the primary endpoint, a confidence-interval method, or a hypothesis test.

What do the adverse-event counts represent?

The safety record gives group-level counts for participants at risk and affected in serious and other adverse-event categories, along with a death count. Counts describe how many participants are recorded in each category; they do not, on their own, quantify event timing, duration, recurrence, or causation. A serious adverse event is not necessarily treatment-related, and a death count is not evidence that treatment caused the deaths. The registry lists fever and pericardial effusion among the top serious terms with percentages, but does not provide corresponding term-specific counts or the detailed event narratives in the information recorded.

What can planning calculations say?

In general, sample-size planning uses assumptions about the effect to detect, variability, significance level, allocation, and analysis method. A planning illustration based on an observed effect is not the same as an original design justification, and it is not observed power. The registry record does not report the study's sample-size justification or its own statistical design assumptions. It also does not report interim analyses or stopping rules. None of those features should be inferred from the fact that the study was terminated.

In short, the outcome definition is detailed enough to explain what the primary endpoint was intended to measure, while the analysis information needed to reproduce or evaluate an estimate is not reported. The study's single-group design also limits what any within-group outcome can establish about comparative effects.

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("EGF816 + Gefitinib")
n      <- c(11)
events <- c(7)
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  EGF816 + Gefitinib  11  7  63.6  30.8  89.1  35.4  84.8  34.9  84.8

11. Multiplicity, Missing Data and Analysis Populations

The registry lists a primary endpoint and several secondary outcomes: overall response rate, median overall survival, median progression-free survival, and treatment-related adverse events. Considering multiple outcomes raises a general statistical issue: if several tests are conducted, the chance of at least one apparently notable result can increase unless the analysis plan accounts for multiplicity. The registry record does not report whether formal hypothesis tests were planned, whether an adjustment was intended, or whether outcomes were ordered in a testing hierarchy. No such plan should be inferred.

The registry record does not report how missing data were handled for the primary endpoint or secondary outcomes. It does not state how participants without a 9-month assessment were treated, how censoring was defined, or which analysis population was used. These omissions matter because the denominator and classification of participants affect a fixed-time rate. The number enrolled is not necessarily the number included in an endpoint analysis.

The record lists no analyses and does not report whether the analysis was intention-to-treat, per-protocol, or based on another population definition. It also does not describe a method for handling treatment discontinuation, incomplete follow-up, or unavailable outcome assessments. These are unreported analysis details, not evidence that particular methods were or were not used outside the registry record.

Without a reported multiplicity strategy, missing-data rules, and analysis population, readers cannot determine how the listed outcomes were analyzed or how robust any estimate would be to alternative analytic choices. The registry record does not provide outcome analyses with which to assess those issues.

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 0% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: fever (9.1%), pericardial effusion (9.1%).

The serious adverse-event figures list 11 participants at risk and 2 affected in the EGF816 plus gefitinib group. The other adverse-event figures list 11 at risk and 11 affected. The registry also lists 4 deaths. These are descriptive counts recorded for the group; they should not be read as evidence that the drugs caused the events or deaths.

Fever and pericardial effusion are listed as the top serious adverse-event terms, each with a reported percentage of 9.1%. The registry record does not give term-specific counts in the information available, nor does it explain the event-level details behind these percentages. The percentage entries should therefore be reported as listed rather than translated into an inferred number of participants.

The record does not describe the timing of events relative to treatment, duration, recurrence, severity gradations beyond the serious classification, or the assessment of causal relationship. It also does not state how long participants were followed for safety. The “other” adverse-event category should be kept distinct from the serious category unless the registry provides a definition; that definition is not reported. These safety figures provide limited descriptive context, not a comparative safety estimate.

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

The registry record identifies a study of EGF816 plus gefitinib in TKI-naïve EGFR-mutant non-small cell lung cancer and specifies a primary endpoint focused on progression-free status at 9 months. It also describes the study as phase 2, single-group, unmasked, and terminated. These details explain the planned clinical question and the setting in which outcomes were intended to be assessed.

The record does not report the 9-month progression-free rate, an endpoint denominator, or a confidence interval. It also lists no analyses. Therefore, the record cannot show how many participants met the primary endpoint, how uncertain an estimate might be, or whether an observed result differed from a prespecified benchmark. The reason the study was terminated is also not reported.

Even if a numerical outcome for the single group were available, it would describe that group's observed experience. Without a comparator, it would not establish a treatment difference relative to another approach. A single-group study cannot, by design alone, rule out other explanations for an observed outcome. The absence of a comparative result should not be replaced with a causal claim.

The adverse-event counts provide some safety information, but they do not establish treatment causation. The record does not give sufficient event-level detail to assess timing, duration, or attribution. Deaths listed in the safety record should not automatically be interpreted as treatment-related deaths.

Accordingly, the defensible interpretation is limited to the registry's description of the design, endpoint definition, enrollment, status, and recorded safety counts. Claims that the combination improved outcomes, failed to improve outcomes, or caused a particular safety outcome are not supported by the outcome information reported in the registry record.

14. Why This Trial Matters Statistically

This study illustrates the distinction between a well-defined clinical endpoint and a reported result. The registry describes a 9-month progression-free rate and specifies how objective progression was to be assessed using RECIST 1.1. Those details help clarify what the primary outcome was intended to capture. But an endpoint definition does not substitute for the observed rate, its denominator, or a measure of uncertainty.

It also illustrates why design labels matter. A single-group study can describe outcomes among participants receiving the combination, but it does not create a randomized treatment contrast. The absence of a comparator changes the scope of the statistical question: the record cannot provide a randomized estimate of how outcomes differ under another strategy.

The study's termination status adds context but does not explain the missing outcome analyses or identify the reason for stopping. Without a reported statistical analysis plan, readers also cannot judge how missing follow-up, multiple outcomes, or analysis populations were addressed. Those are not minor details for interpreting a fixed-time rate; they help determine what the estimate means and how precisely it represents the intended population.

Finally, safety counts are informative as recorded events, but their interpretation requires restraint. Counts do not establish causality, and term-level percentages without corresponding detailed counts or timing cannot support a full assessment of event patterns. The record is therefore statistically important as an example of how registration details may define a study question while leaving the outcome evidence needed to answer it unreported.

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 most important limitation for interpretation is that the registry record does not report the primary endpoint result. It gives no 9-month progression-free rate, analysis denominator, confidence interval, or statistical test. No analyses are listed, and results for the listed secondary outcomes are not reported. The clinical outcome question therefore remains unanswered by the posted registry information.

The design is single-group, with no separate comparator, and the allocation field is NA. As a result, the record does not provide a randomized comparison or a treatment-effect contrast. Masking is listed as none. The record does not explain how outcome assessments were conducted or whether any review process helped limit assessment bias.

Although enrollment is listed as 11, the registry does not report the number included in the primary endpoint analysis, the amount of missing follow-up, or how missing assessments were handled. The analysis population, treatment exposure, duration of follow-up, and rules for censoring are also not reported. These omissions limit assessment of how representative or precise a potential endpoint estimate would be.

The registry does not report the sample-size justification, statistical analysis plan, multiplicity approach, interim analyses, or stopping rules. The reason for termination is not reported either. The safety information is limited to aggregate counts and selected terms; detailed event timing, attribution, and outcome information are not reported. These limitations constrain both efficacy interpretation and safety assessment, without establishing that a particular result or explanation is absent from other records.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: A Study of EGF816 and Gefitinib in TKI-naïve EGFR-mutant Non-Small Cell Lung Cancer — NCT03292133.
• Registry record last updated 2025-06-10; status last verified 2025-05.
• Results first posted 2025-06-10.
• 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 describes NCT03292133, a phase 2, single-group study of EGF816 plus gefitinib in TKI-naïve EGFR-mutant non-small cell lung cancer. It lists enrollment of 11, no masking, and TERMINATED status. The start date is 2017-10-31, and the primary completion date is 2021-12-31.

The primary outcome is the 9-month progression-free rate, defined as the percentage free from objective progression or death at 9 months after treatment begins, with progression evaluated using RECIST 1.1. Secondary outcomes include response, survival, progression-free survival, and treatment-related adverse events.

The primary endpoint result and secondary outcome results are not reported in the registry record, and no analyses are listed. The record gives serious adverse-event, other adverse-event, and death counts, but does not establish causation. The reason for termination, analysis populations, missing-data methods, and statistical plan are not reported.