BIBW 2992 and BSC Versus Placebo and BSC in Non-small Cell Lung Cancer Patients Failing Erlotinib or Gefitinib (LUX-LUNG 1): Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for BIBW 2992 and BSC Versus Placebo and BSC in Non-small Cell Lung Cancer Patients Failing Erlotinib or Gefitinib (LUX-LUNG 1) (NCT00656136), a randomized phase 3 study. The primary outcome is Overall Survival.

2. Clinical Question

The registry describes a population whose cancer had progressed following prior targeted treatment with erlotinib or gefitinib and prior cytotoxic chemotherapy. The primary question is thus specific to that treatment history and should not be generalized to patients with other treatment histories based on this record alone. The trial was randomized and double-blind, which are design features intended to support a fair comparison and limit the influence of knowledge of assignment. They do not, by themselves, establish the size or precision of any treatment difference.

The posted record gives an enrollment of 585 and lists overall survival as the primary outcome. It also names progression-free survival and objective response rate as secondary outcomes. Numerical results for these endpoints are not reported in the registry record. The clinical question can therefore be described from the design, but the direction and magnitude of the observed survival comparison cannot be stated from the available outcome information.

3. Trial Design

The record identifies LUX-LUNG 1 as a randomized, double-blind, parallel-group Phase 3 trial. Its official title describes it as a Phase IIb/III trial. The stated enrollment is 585, and the registry status is completed. The study began in 2008-04, and primary completion is listed as 2013-10.

Eligible patients had non-small-cell lung cancer and had received one or two lines of cytotoxic chemotherapy, at least one of which contained platinum. They also had to have received gefitinib or erlotinib for at least 12 weeks and then experienced progression. Both groups received best supportive care. One group received BIBW 2992 tablets once daily; the other received placebo once daily. The registry describes treatment and follow-up as continuing until death or loss to follow-up.

Random allocation is intended to balance prognostic characteristics across groups on average, while double masking is intended to reduce the influence of treatment knowledge on care and assessment. These design features help frame the comparison, but the registry record does not describe the allocation procedure or the specific masking arrangements. Further details of these procedures are not reported in the registry record.

The primary endpoint was overall survival. The timeframe is described as randomization until death or the last patient out date, with an average of 12 months. The record separately describes an analysis cutoff of 08 July 2010 for the primary analysis and 04 October 2013 for the final analysis. It reports that 11 patients were lost to follow-up for the primary analysis and 13 for the final analysis, with those patients censored at their last contact when known to be alive.

The registry does not report the planned sample-size justification, the allocation ratio, or a detailed statistical analysis plan. The reported enrollment alone does not establish how the planned study size was chosen or how precisely the primary comparison was expected to be estimated.

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.

Before assignment: Two-arm, randomised (2:1 ratio), double-blind , placebo-controlled, multi-centre trial. 585 patients were randomised. All patients randomized received at least one dose of study medication.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: Randomized set was all patients who were randomized and for this study all of these patients received at least one dose of study medication.

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: Randomized Set (RS) included all patients randomised to receive treatment

6. Primary Endpoint

The registry lists the primary outcome as Overall Survival, measured over From randomization until death or the last patient out date, an average of 12 months.

Overall survival measures the time from randomization until death. In this trial, the registry says that patients who were alive were censored at their last contact date before database lock. This endpoint captures the duration of survival after assignment to a study group, rather than a change in a laboratory measure or a tumor response at a single assessment.

Time-to-event endpoints are useful when participants may have different lengths of follow-up or when some are still alive at the analysis cutoff. Censoring records that a participant was known to be alive up to a particular contact, without treating that contact as a death or asserting what happened afterward. Interpretation relies on the event-time analysis accounting appropriately for such censoring. The registry describes the censoring dates and the number lost to follow-up for the primary and final analyses, but does not provide enough information to evaluate all assumptions used in the analysis.

The registry specifies the endpoint as a median with a 95% confidence interval. In general, a median survival estimate is the time by which half the analyzed group has experienced the event, under the time-to-event estimate. A confidence interval expresses uncertainty around that estimate; it is not a range containing a known fixed proportion of individual survival times. Neither group’s median nor its confidence interval is reported in the registry record.

Overall survival is the primary outcome named in the record, with progression-free survival and objective response rate listed as secondary outcomes. The posted information does not give numerical estimates for these outcomes, so it does not allow the size or precision of the survival comparison to be characterized.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

Overall survival is a time-to-event endpoint. Each participant contributes a duration from randomization until death or, if death is not observed, until the last known contact while alive. The registry says living participants were censored at their last contact date before database lock. Censoring is not the same as assigning a survival time equal to the last contact or assuming that the participant died then. It indicates that the event was not observed during the known follow-up period.

What does a median survival estimate describe?

In general, the median is the point at which the estimated survival probability reaches one half. It is a summary of the estimated time-to-event distribution, not an average survival time and not a statement that every participant experiences the event by that time. Its interpretation depends on the observed event and censoring pattern. The registry names the median as the primary endpoint parameter, but does not report the group medians.

What does a confidence interval add?

A confidence interval describes statistical uncertainty in an estimate under the method’s assumptions. A narrower interval generally indicates greater precision than a wider one, while neither interval width nor an estimate alone says whether an outcome is clinically important. The registry specifies a 95% confidence interval for the median, but the interval limits are not reported in the registry record. There is therefore no reported interval with which to assess the precision of either group’s median.

How should hazard ratios be understood?

In general, a hazard ratio compares the event rates between groups over time, as represented by a time-to-event model. It is not a ratio of median survival times, and it does not directly state how many months an individual gains or loses. Its interpretation depends on the model and on whether the relative event rate is adequately represented over follow-up. The registry record does not report a sponsor hazard ratio or describe the model used to estimate one. No hazard ratio should be inferred from the endpoint definition.

Why does censoring matter?

Time-to-event methods can use information from participants who have not experienced the event by the analysis cutoff, rather than discarding them outright. Their follow-up contributes up to the time they were last known to be alive. This approach relies on assumptions about censoring and follow-up; for example, the censoring process should not make the remaining observed participants systematically unrepresentative in ways unaccounted for by the analysis. This is a general statistical consideration, not a claim about whether the trial met that assumption. The record reports censoring for patients lost to follow-up, but does not describe diagnostic checks or sensitivity analyses.

What can be concluded from the analysis dates?

The primary analysis cutoff is listed as 08 July 2010, and the final analysis cutoff as 04 October 2013. A later cutoff can allow additional follow-up and events to accrue, but the dates alone do not show how the estimates changed. The record notes 11 patients lost to follow-up for the primary analysis and 13 for the final analysis. It does not state the total deaths, event distribution, or survival estimates at either cutoff.

How should study size be interpreted?

Enrollment is not a measure of observed statistical power. In time-to-event studies, information for the comparison depends importantly on the number and timing of events, as well as follow-up and analysis choices. The registry record gives enrollment but does not report a sample-size justification, planned event target, or power calculation. Any sample-size illustration based on an observed effect would be a planning exercise, not evidence that the trial had a particular observed power. Such an illustration also cannot supply missing outcome estimates.

The registry does not report the statistical test, model specification, handling of ties, covariate adjustment, or any assumption checks for the primary analysis. These details are not established merely by a median endpoint and confidence interval being named. General statistical descriptions above explain common concepts; they do not identify the methods actually used in this trial.

10. Multiplicity, Missing Data and Analysis Populations

The registry names overall survival as the primary outcome and lists progression-free survival and objective response rate as secondary outcomes. It also records 3 outcome measures and 4 analyses, but does not explain how those analyses map to endpoints, time points, or analysis populations. The statistical plan for handling multiple endpoints or multiple analyses is not reported in the registry record.

Multiplicity is a general concern when several statistical comparisons are made: the chance of at least one apparently notable result can increase unless the analysis plan accounts for the set of comparisons. The record does not state whether any adjustment, hierarchical testing procedure, or prespecified ordering was used. It is therefore not possible to determine how multiplicity was addressed or how it should affect interpretation of any secondary results.

For missing survival follow-up, the record says that patients known to be alive were censored at their last contact. It reports 11 patients lost to follow-up in the primary analysis and 13 in the final analysis. The record does not describe additional methods for missing data, sensitivity analyses, or assessment of the assumptions underlying censoring. The reported numbers should not be treated as deaths.

The primary analysis population is described as the randomized set, consisting of all randomized patients; for this study, all received at least one dose of study medication. The record does not describe other analysis populations or explain whether analyses used different inclusion rules. It also does not report how protocol deviations, withdrawals, or other missing information were handled beyond the stated censoring approach.

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: diarrhoea (4.6%), malignant neoplasm progression (4.1%), pleural effusion (3.6%), metastases to central nervous system (2.8%), pneumonia (2.6%).

The registry lists adverse-event groups titled Placebo and Afatinib 50 mg/Day. The treatment description elsewhere names BIBW 2992; the safety group label is reproduced as written in the record, without assuming an explanation for the difference in wording. The listed numbers at risk for serious adverse events are 195 for Placebo and 390 for Afatinib 50 mg/Day. The numbers affected are 36 and 136, respectively. For other adverse events, the numbers at risk are 195 and 390, and the numbers affected are 167 and 383, respectively.

These are counts, not adjusted comparisons. The registry does not provide a statistical contrast or uncertainty interval for these figures, and the counts alone do not establish that treatment caused an event. The listed top serious adverse-event terms and percentages are diarrhoea, 4.6%; malignant neoplasm progression, 4.1%; pleural effusion, 3.6%; metastases to central nervous system, 2.8%; pneumonia, 2.6%; and respiratory failure, 2.3%. The record does not explain further how these terms were selected or provide additional detail about event timing or severity grades.

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

The record establishes the question the trial was designed to address: overall survival following randomization to BIBW 2992 plus best supportive care or placebo plus best supportive care in patients with non-small-cell lung cancer after progression on erlotinib or gefitinib. It also describes the randomized, double-blind, parallel-group design, the eligibility context, and the censoring approach for survival follow-up.

It does not provide the primary outcome estimates. Without the median survival values, confidence intervals, or sponsor-reported hazard ratio, the posted information does not show the direction or size of the observed survival contrast or its precision. The same limitation applies to the secondary outcomes, for which numerical estimates are not reported in the registry record. The completed status and enrollment figure do not fill this gap.

Even when endpoint estimates are available, statistical evidence and clinical importance are different questions. A confidence interval expresses uncertainty under the analysis assumptions; it does not by itself determine whether an effect matters to patients. A hazard ratio summarizes relative event experience, not an individual prediction or a direct measure of time gained. These are general principles and cannot be used to infer the missing trial results.

The safety counts describe the numbers affected in the listed groups, and the serious-event terms have associated percentages. They should be read as descriptive registry figures, not as proof of causation or as a complete safety comparison. The record does not give enough information to make a full assessment of safety outcomes.

Accordingly, the registry information supports an account of the trial’s design and endpoints, but not a conclusion about whether the observed primary or secondary outcomes favored either group. A complete interpretation would require the numerical results and relevant analysis details, none of which should be reconstructed from the design description alone.

13. Why This Trial Matters Statistically

This trial illustrates the distinction between a clearly specified clinical question and a reportable statistical result. The record describes randomization, masking, parallel groups, the target population, and an overall-survival endpoint. Those details show what comparison was planned, but the absence of endpoint estimates prevents an assessment of the observed effect and its precision.

For time-to-event outcomes, follow-up and censoring are central to interpretation. The record identifies when patients were censored and gives the number lost to follow-up at the primary and final analyses. These details help readers understand how incomplete observation was represented, while leaving important questions unanswered about the total event experience and the assumptions used in analysis.

The distinction between enrollment and event information is also important. A trial may enroll many participants yet still have limited information for a survival contrast if the number or timing of observed events is insufficient; conversely, enrollment alone cannot establish the amount of statistical information. The record does not report an event target or sample-size justification, so its enrollment should not be interpreted as evidence about planned or achieved power.

Finally, the listed secondary outcomes and analyses raise questions about multiplicity and analysis choices. The record does not describe how multiple outcomes or analyses were handled. This trial therefore provides a useful example of why statistical interpretation depends on more than design labels: estimates, uncertainty, analysis methods, missing-data handling, and the relationship among outcomes all contribute to understanding what the evidence shows.

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 primary limitation for interpreting the clinical result is that the registry record does not report the primary survival estimates or their uncertainty. Group-specific medians, 95% confidence intervals, sponsor hazard ratio, and a primary outcome p-value are not reported in the registry record. Numerical results for the listed secondary outcomes are also absent. This prevents a description of the observed efficacy comparison.

The record gives two analysis cutoff dates and reports different counts of patients lost to follow-up for the primary and final analyses. It does not provide the number of deaths, the amount of follow-up by group, or an account of how the survival estimates changed between analyses. It also does not describe sensitivity analyses for loss to follow-up or evaluate the assumptions behind censoring.

Several analysis details are not reported in the registry record, including the statistical test or model, covariate adjustments, planned event target, sample-size justification, and multiplicity procedure. The record also does not explain the mapping of the 4 analyses to the 3 outcome measures. These omissions limit assessment of prespecification and the statistical properties of any comparisons.

The safety information is likewise limited to group counts and selected serious adverse-event terms with percentages. Further details about event definitions, timing, grading, and statistical comparisons are not reported in the registry record. In addition, the safety group title Afatinib 50 mg/Day differs from the intervention name BIBW 2992 elsewhere in the record; the record does not explain this labeling difference.

Finally, the eligibility description defines a specific treatment-history population. The registry information does not support extending conclusions to populations with different disease or treatment histories.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: BIBW 2992 and BSC Versus Placebo and BSC in Non-small Cell Lung Cancer Patients Failing Erlotinib or Gefitinib (LUX-LUNG 1) — NCT00656136.
• Registry record last updated 2016-07-26; status last verified 2016-06.
• Results first posted 2013-11-27.
• 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

LUX-LUNG 1 is described as a randomized, double-blind, parallel-group Phase 3 study; the official title calls it a Phase IIb/III trial. The registry lists 585 participants and compares once-daily BIBW 2992 plus best supportive care with once-daily placebo plus best supportive care in non-small-cell lung cancer after progression on gefitinib or erlotinib.

Overall survival is the primary endpoint, measured from randomization until death and summarized as a median with a 95% confidence interval. The record describes censoring of participants known to be alive at their last contact and lists primary and final analysis cutoff dates. Progression-free survival and objective response rate are secondary outcomes.

Numerical efficacy estimates and key analysis details are not reported in the registry record. The available information therefore describes the design and outcome definitions but does not establish the observed treatment effect or its precision.