Study of Vandetanib Combined With Chemotherapy to Treat Advanced Non-small Cell Lung Cancer: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Study of Vandetanib Combined With Chemotherapy to Treat Advanced Non-small Cell Lung Cancer (NCT00687297), a randomized phase 2 study. The primary outcome is Progression-free Survival.

2. Clinical Question

3. Trial Design

This was a randomized, phase II, parallel-group study. The registry classifies masking as quadruple, but does not report which study roles were masked or how masking was maintained. The sponsor was PrECOG, LLC. The study is recorded as completed, with enrollment of 162 participants. Its recorded start was 2008-04 and primary completion was 2011-01.

The official study title describes vandetanib in combination with docetaxel and carboplatin, followed by placebo or vandetanib maintenance, in patients with IIIb, IV, or recurrent non-small cell lung cancer. Both arm descriptions specify the same induction treatment: docetaxel and carboplatin on day 1, alongside daily vandetanib on days 1 through 21, in a 28-day cycle for four cycles. Participants without progression after those cycles received their assigned maintenance treatment daily until progression.

This sequence matters when interpreting the randomized contrast. The maintenance assignment distinguishes the strategies after induction; the record does not describe a randomized comparison of vandetanib induction against induction without vandetanib. The primary endpoint population is identified as all randomized patients. The record does not describe the randomization procedure, allocation ratio, stratification factors, or the number randomized to each arm. It also does not explain how participants who progressed during induction contributed to each treatment comparison.

The registry lists objective response rate and progression-free survival among the secondary outcomes, in addition to identifying progression-free survival as primary. It records three outcome measures and two analyses, but gives no further details about the analyses in the available information. Comparative results for the primary endpoint are 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.

Randomization

Reasons for not completing this period:

Induction

Reasons for not completing this period:

Maintenance

Analysis population for the primary outcome, as defined in the registry: All randomized patients were included.

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 Progression-free Survival, measured over Assessed every 2 cycles (1 cycle = 3 weeks during induction and 4 weeks during maintenance)).

Progression-free survival measures the time from randomization, before induction, to the first evidence of disease progression or death without progression. A participant who remained alive without documented progression was censored at the date of the last disease evaluation. The endpoint was assessed every two cycles; the registry describes a cycle as 3 weeks during induction and 4 weeks during maintenance.

As a time-to-event endpoint, progression-free survival uses both the timing of events and information from participants who have not had an event by their last assessment. Censoring allows those participants to contribute information up to the time their status was last evaluated, rather than treating their follow-up as if an event had occurred. In general, this approach is useful when follow-up duration differs among participants and the event of interest may occur at different times.

The primary outcome is summarized in the record as a median with a 95% confidence interval, and the stated population is all randomized patients. In general, the median describes the time by which half the population has experienced the event under the endpoint definition. A confidence interval conveys statistical uncertainty around an estimate; it does not by itself show whether a treatment difference is clinically important. The registry record does not report the arm-specific medians, confidence intervals, or a comparative estimate, so the size and precision of any difference cannot be assessed from the recorded information.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The statistical methods can be understood from the endpoint definition and the types of information the registry does and does not report. The endpoint is time to progression or death without prior progression, with censoring for participants alive and progression-free at their last disease evaluation. The record summarizes the primary endpoint using a median and a 95% confidence interval. It does not provide the values for either randomized group, or a comparative estimate.

What does a median time-to-event estimate describe?

In general, a median time-to-event estimate identifies the time at which the estimated event-free proportion reaches the halfway point. It uses the ordering of event times and the follow-up information contributed by participants who are censored. It is different from a simple average of observed times: censoring means that the eventual event time is unknown for some participants, and their recorded follow-up cannot be treated as a complete event time.

A median is one summary of the time-to-event pattern. It does not describe every feature of the pattern, and two groups can have different event-time distributions even if their medians are similar. For that reason, comparative analyses may use an additional measure, such as a hazard ratio, but the registry record does not report a hazard ratio for this study. No assumptions about the analysis model or its adequacy can be assessed from the available information.

What does censoring contribute?

According to the endpoint description, participants alive without progression were censored at their last disease evaluation. In general, censoring retains information that a participant was event-free up to that evaluation; it does not mean that the participant had no later progression. Standard time-to-event methods rely on assumptions about how censoring relates to the future event process. The registry record does not describe censoring patterns, follow-up completeness, or checks of those assumptions.

Assessment was scheduled every two cycles, with cycle duration described as 3 weeks during induction and 4 weeks during maintenance. The record does not report the number or timing of actual assessments, missed assessments, or any rules for handling progression dates between evaluations. Those details would help readers understand how event timing was recorded and how incomplete follow-up affected the analysis.

How should confidence intervals be read?

In general, a confidence interval expresses uncertainty around an estimated quantity under the statistical procedure used. A narrower interval indicates greater precision than a wider interval, while the interval's location describes the range of values compatible with the estimate under that procedure. A confidence interval is not a guarantee about the true value, and it does not answer questions about clinical importance by itself. The registry identifies a 95% confidence interval for the primary endpoint but does not report its endpoints, so neither precision nor compatibility with particular treatment effects can be evaluated.

Why is a hazard ratio not interchangeable with a median?

In general, a median summarizes an event-time distribution at a particular point, whereas a hazard ratio compares event rates over follow-up under a model. These measures answer related but distinct questions and can yield different impressions when the event patterns change over time. Interpreting a hazard ratio also depends on modeling assumptions. The registry record's general description of time-to-event calculations says that only sponsor-reported hazard ratios are used, but it contains no hazard ratio result for this trial. No recalculated estimate can therefore be interpreted from the available information.

What can planning calculations say?

In general, sample-size planning illustrations describe how many participants or events might be needed under stated assumptions about an effect, significance level, allocation, and statistical approximation. Such illustrations are conditional planning exercises, not results from the trial and not observed power. The record describes an illustration based on a fraction of the observed effect, with a two-sided significance level of 0.05, equal allocation, and a normal approximation. It does not give the resulting planning values or the observed effect in the information. The trial's own sample-size justification is not reported in the registry record.

These methods concepts explain how a time-to-event analysis is usually interpreted, but they do not fill in missing trial results. Without the observed estimates, confidence intervals, comparative test results, and analysis details, no conclusion about the direction, magnitude, or precision of the primary comparison is justified.

10. Multiplicity, Missing Data and Analysis Populations

The registry identifies progression-free survival as the primary outcome and also lists progression-free survival and objective response rate among secondary outcomes. It records three outcome measures and two analyses. The available information does not identify all outcome measures, explain how the listed analyses relate to each outcome, or specify whether any analysis was primary, secondary, exploratory, or adjusted.

When a study tests several outcomes or comparisons, the chance of at least one apparently notable result can increase. In general, multiplicity procedures can control or describe that issue by specifying which comparisons are confirmatory and how statistical error is managed. The registry record does not report a multiplicity strategy, a hierarchy of tests, an adjustment method, or an interim-analysis plan. None should be inferred from the phase, design, or number of analyses recorded.

The primary endpoint description states that all randomized patients were included. This identifies the intended primary population in the record, but the number randomized in each arm and the analysis details are not reported. The safety summaries separately give treated counts for induction and maintenance; those treatment counts should not be assumed to define the primary efficacy population. The registry does not explain how treatment discontinuation, progression during induction, or other post-randomization events were handled in the efficacy analysis.

The endpoint definition specifies censoring of participants alive without progression at their last disease evaluation. That is the only stated handling of incomplete time-to-event observation in the available description. Other missing-data methods, rules for missing assessments, sensitivity analyses, and the amount of missing outcome information are not reported in the registry record. The record also does not explain whether any participants were excluded from particular analyses or how such exclusions were handled.

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: neutrophil count decreased (41.4%), leukocytes increased (15.9%), rash/desquamation (15.6%), diarrhea w/o prior colostomy (9.4%), dyspnea (9.4%).

The safety information gives separate counts for participants treated during induction and those treated on each maintenance regimen. In the all-treated induction group, 157 were at risk for the reported summaries; 111 were recorded as affected by serious adverse events and 145 by other adverse events. In the vandetanib maintenance group, the corresponding at-risk count was 32, with 22 affected by serious events and 29 by other events. In the placebo maintenance group, the at-risk count was 26, with 11 affected by serious events and 22 by other events.

These are counts from differently defined treatment groups and periods. The induction group and maintenance groups should not be combined: maintenance groups follow the induction period, and the available record does not provide a common denominator or analysis for a combined comparison. The counts alone do not describe event timing, duration, severity beyond the serious-event classification, or whether an individual experienced more than one event. Death counts are not reported in the registry record.

The registry lists serious-event terms with percentages, including neutrophil count decreased at 41.4%, leukocytes increased at 15.9%, rash/desquamation at 15.6%, diarrhea w/o prior colostomy at 9.4%, dyspnea at 9.4%, and pruritus/itching at 9.4%. The record does not specify the denominator for these percentages in the available information. These figures should therefore be read as reported term frequencies, not as a basis for calculating comparative risks or drawing causal conclusions.

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

This randomized phase II study addresses a specific treatment sequence for patients with IIIb, IV, or recurrent non-small cell lung cancer. Both described groups received induction with vandetanib, docetaxel, and carboplatin. For participants without progression after four cycles, the assigned maintenance was either vandetanib or placebo. The primary outcome was progression-free survival from randomization before induction to progression or death without progression.

The record does not report the primary outcome estimates or a between-group comparison. It therefore does not show whether the maintenance strategies differed, in which direction a difference might lie, or how precisely an effect was estimated. It also does not report objective response rate results. A missing result cannot be interpreted as a null result, and the record does not demonstrate equivalence or lack of difference.

The safety summaries report affected-participant counts for the treated groups and selected serious adverse-event terms with percentages. Those figures describe the reported summaries but do not, on their own, establish that a treatment caused an event. The groups have different denominators and represent different treatment periods; a direct comparison would require appropriate outcome definitions, denominators, and analysis details. The record also does not give a death count.

More generally, a trial result must be read in light of the randomized comparison, endpoint definition, analysis population, missing follow-up, precision, and potential multiplicity. Several of these details are not reported in the registry record, and the comparative results are absent. The study description alone supports understanding what was planned and how the endpoint was defined, not a conclusion about treatment effects. No medical decision should be based on these incomplete registry entries alone.

13. Why This Trial Matters Statistically

This study illustrates why the treatment contrast must be identified from the full treatment sequence. Both groups received vandetanib during induction with docetaxel and carboplatin. The randomized distinction described in the arms is maintenance with vandetanib or placebo for participants free of progression after induction. Describing the comparison simply as vandetanib versus no vandetanib would obscure that shared induction exposure and misstate the question.

It also shows why outcome definitions and analysis populations matter. Progression-free survival begins at randomization, before induction, and includes progression or death without progression as events. The primary population is stated to include all randomized patients, while the safety summaries use treated groups and separate induction from maintenance. Those populations answer different descriptive questions and should not be treated as interchangeable.

For time-to-event outcomes, censoring and follow-up contribute to the estimate alongside observed events. The registry gives a censoring rule and a schedule for assessment, but does not report arm-specific estimates, confidence intervals, or comparative results. Without those statistics, neither the magnitude nor precision of the randomized comparison can be evaluated. That limitation is substantive: design information identifies the question, but it cannot substitute for outcome evidence.

Finally, the record identifies multiple outcome measures and analyses without detailing the analysis plan or multiplicity handling. This makes it difficult to determine how the reported analyses were prioritized or how uncertainty across outcomes was managed. The trial is therefore statistically informative as an example of a maintenance comparison after common induction, while the available record is insufficient to assess its primary comparative result.

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 main limitation of the available registry information is the absence of comparative primary-outcome results. Arm-specific progression-free survival medians, confidence intervals, and a treatment comparison are not reported in the registry record. Objective response rate results are also absent. Without these values, the effect's direction, magnitude, and precision cannot be assessed.

The record states that all randomized patients were included in the primary population but does not report the number randomized to each group, the allocation procedure, or the analysis details. The enrollment total is 162, while the safety summaries include 157 treated during induction and smaller treated maintenance groups. The information does not explain the relationship between these counts or how participants who did not reach maintenance were represented in efficacy analyses.

Details that could inform interpretation are not reported, including a sample-size justification for the trial, the full statistical analysis plan, handling of multiplicity, interim analyses, missing-data procedures beyond the stated censoring rule, and sensitivity analyses. The schedule for assessment is given, but actual follow-up completeness and missed assessments are not described.

Safety summaries provide group counts and selected serious-event terms, but the available record does not specify the percentage denominators, event timing, or detailed methods for comparing groups. Death counts are not reported. The registry information therefore supports only a limited descriptive reading of safety and design; it does not support a full comparative assessment of efficacy or safety.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Study of Vandetanib Combined With Chemotherapy to Treat Advanced Non-small Cell Lung Cancer — NCT00687297.
• Registry record last updated 2018-05-30; status last verified 2018-04.
• Results first posted 2012-07-10.
• 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.

18. Record Summary

NCT00687297 is a completed randomized phase II parallel-group study sponsored by PrECOG, LLC. The registry reports enrollment of 162 participants, a start date of 2008-04, and primary completion in 2011-01. The study enrolled patients with IIIb, IV, or recurrent non-small cell lung cancer and compared maintenance strategies after a shared induction regimen of vandetanib, docetaxel, and carboplatin.

The primary outcome was progression-free survival, defined from randomization before induction to progression or death without progression, with censoring at the last disease evaluation for participants alive without progression. All randomized patients were identified as the primary population. The record lists objective response rate and progression-free survival among secondary outcomes.

Comparative primary-outcome estimates and objective response results are not reported in the registry record. Safety summaries describe treated induction and maintenance groups and selected serious adverse-event terms. The available information is insufficient to assess the magnitude or precision of the randomized efficacy comparison.