A Study of Pemetrexed and Cisplatin, in Non Small Cell Lung Cancer: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for A Study of Pemetrexed and Cisplatin, in Non Small Cell Lung Cancer (NCT01000480), a na phase 2 study. The primary outcome is 1 Year Progression Free Survival.

2. Clinical Question

3. Trial Design

This completed Phase 2 study evaluated a treatment sequence for participants with locally advanced, unresectable, Stage III, nonsquamous non-small cell lung cancer. Pemetrexed and cisplatin were given as induction therapy, followed by pemetrexed and cisplatin with concurrent thoracic radiotherapy. The registry record reports enrollment of 90 participants and identifies the design as single-group, with allocation listed as not applicable and masking listed as none.

Because the study has a single group, its outcome data describe participants treated under the study regimen. They do not, by themselves, estimate how outcomes would compare with a separate control treatment or with no treatment. The record explicitly cautions that the arms are not a like-for-like control comparison; no randomized comparison is described.

The primary outcome was 1-year progression-free survival, expressed as a percentage of participants. The stated time frame describes assessment from the date of first dose through objectively determined progressive disease or death, with assessments every cycle up to 4 cycles and then every 3 months up to 1 year; a cycle is stated to be 21 days. Overall survival and the number of participants with an objective tumor response are listed as secondary outcomes.

The registry record identifies Eli Lilly and Company as sponsor and gives the study status as completed. It does not report the observed primary outcome value, its confidence interval, or details of a statistical analysis plan. The results therefore support a description of the recorded design and outcome definitions, but not an estimate of comparative treatment effects.

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: Study treatment had 2 phases and follow-up. Induction phase: 2 cycles of pemetrexed-cisplatin. Then, if eligible, the concurrent phase: 2 more cycles of pemetrexed-cisplatin and thoracic radiotherapy. Follow-up period: Started when treatment discontinued or completed, and lasted up to 2 years after first dose of pemetrexed.

Induction Phase

Reasons for not completing this period:

Concurrent Therapy Phase

Reasons for not completing this period:

Follow-Up Period

Analysis population for the primary outcome, as defined in the registry: Intent-to-treat population: participants who received at least 1 dose of either study drug (pemetrexed or cisplatin). The number of participants censored was 35.

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: Intent-to-treat population: participants who received at least 1 dose of study drug (pemetrexed or cisplatin).

6. Primary Endpoint

The registry lists the primary outcome as 1 Year Progression Free Survival, measured over Date of first dose to date of objectively determined PD or death [every cycle up to 4 cycles and then every 3 months up to 1 year (1 cycle=21 days)].

The primary endpoint is 1-year progression-free survival, reported as a percentage of participants. Progression-free survival is the time from study enrollment until the first observation of progressive disease or death from any cause. The endpoint asks what proportion of the defined study population remained alive without documented progression through the stated 1-year time point.

Progression-free survival is used in oncology studies to describe disease control over time while incorporating death as an event. It differs from an endpoint based only on tumor response: a response assessment concerns whether a tumor meets criteria for objective response, whereas progression-free survival also reflects how long participants remain free of progression or death. The registry record lists objective tumor response and overall survival as secondary outcomes.

The registry record describes rules for censoring participants without a recorded progression or death, those who began subsequent systemic anticancer therapy before documented progression or death, and those without a complete baseline disease assessment. These rules affect how follow-up contributes to the endpoint. The number of participants censored was 35.

The primary endpoint is named, but its observed percentage and 95% confidence interval are not reported in the registry record. As a result, the endpoint definition can be explained, but the magnitude and precision of the study's 1-year progression-free survival result cannot be assessed from the record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The study is identified as Phase 2 and single-group. These labels describe the recorded study design; they do not supply a detailed statistical analysis plan. Allocation is listed as not applicable, and masking is listed as none. The registry record does not describe random assignment or a comparator group. The reported outcomes should therefore be understood as observations in the study group, rather than as a randomized treatment contrast.

What does the primary endpoint measure?

The primary endpoint is the percentage of participants with progression-free survival at 1 year. The record defines progression-free survival as time from enrollment to the first observation of progressive disease or death from any cause. This time-to-event definition combines disease progression and death into the event of interest. The endpoint is expressed as a percentage at a specified time point, rather than as a mean duration.

The stated assessment schedule is every cycle up to 4 cycles and then every 3 months up to 1 year. The record states that a cycle is 21 days. In general, scheduled assessments determine when progression can be documented; the true onset of progression may fall between assessments. The registry record does not provide further detail about how assessment timing was incorporated into the analysis.

Why does censoring matter?

Censoring means that a participant's observed follow-up ends without the event being documented during that observed period. The participant's available follow-up still contributes information up to the censoring time, but does not establish what happened afterward. In general, time-to-event methods use such partial follow-up rather than treating every participant without a recorded event as event-free indefinitely.

The registry record specifies censoring rules for participants not known to have died and without objective progression, participants who began subsequent systemic anticancer therapy before documented progression or death, and participants without a complete baseline disease assessment. It reports 35 participants censored. The registry record does not report the timing of censoring or further details about the distribution of follow-up.

In general, valid interpretation of a time-to-event estimate depends on how censoring relates to the chance of experiencing the event. If the reasons for ending observation are associated with future risk, that can affect interpretation. The registry record gives operational rules but does not report an assessment of this assumption.

What does a confidence interval contribute?

The primary outcome specifies a 95% confidence interval. In general, a confidence interval expresses statistical uncertainty around an estimated quantity under the method's assumptions. It is not a guarantee that the true value lies within the interval, nor does it measure the importance of the outcome. A narrow interval indicates greater precision than a wide interval, all else being equal.

Neither the primary estimate nor its confidence interval limits are reported in the registry record. Thus, neither the endpoint's estimated level nor its statistical precision can be assessed. The confidence-interval label alone does not convey a numerical result.

What can the single-group design establish?

A single-group study records outcomes among participants receiving the study regimen. In general, those observations can describe the treatment experience in the enrolled population, but without a concurrent comparison group they do not directly estimate what would have occurred under another treatment. Differences between a study group and an external population may reflect differences in participant characteristics, follow-up, or other aspects of care. The registry record does not specify an external comparison.

The record lists 90 participants as enrolled and defines the primary-outcome population as participants who received at least 1 dose of either study drug. It does not give further detail about exclusions or the number contributing to the primary estimate. The reported enrollment figure should not be taken as a substitute for an analysis denominator that is not stated.

What statistical details remain unavailable?

The registry record lists 3 outcome measures and 1 analysis. It does not report the statistical method used to estimate 1-year progression-free survival, the approach used to calculate its confidence interval, or whether any adjustment was made. It also does not report a statistical plan, a sample-size justification, interim analyses, or a multiplicity procedure. These details should not be inferred from the study phase or outcome labels.

Overall survival and objective tumor response are listed as secondary outcomes, but their numerical results and analysis details are not reported in the registry record. In general, secondary outcomes can provide complementary information, but their interpretation depends on their definitions, analysis methods, and uncertainty estimates. Without those details and results, no further statistical conclusions are warranted.

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("Pemetrexed, Cisplatin, and Thoracic Radiotherapy")
n      <- c(90)
events <- c(48)
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  Pemetrexed, Cisplatin, and Thoracic Radiotherapy  90  48  53.3  42.5  63.9  43.1  63.3  43.1  63.3

11. Multiplicity, Missing Data and Analysis Populations

The registry record lists 3 outcome measures, with 1 analysis. The primary outcome is 1-year progression-free survival; overall survival and the number of participants with an objective tumor response are identified as secondary outcomes. The record does not describe whether the outcomes were tested using a prespecified hierarchy, whether any adjustment for multiple comparisons was planned, or how results across outcomes were to be interpreted. A multiplicity strategy is therefore not reported in the registry record.

In general, evaluating multiple outcomes can increase the chance of finding an apparently notable result by chance if each is examined separately. A prespecified strategy helps clarify which results are confirmatory and how uncertainty should be interpreted. This general concern does not establish that a particular error occurred in this study; the relevant analysis plan is not reported.

The registry record defines the primary-outcome population as participants who received at least 1 dose of either study drug. It states that 35 participants were censored for the progression-free survival endpoint and gives rules for censoring in specified circumstances. It does not report the number included in the primary estimate, the amount of missing outcome information, or any imputation method. The record also does not describe sensitivity analyses for missing or censored data.

The definition says participants without a complete baseline disease assessment were censored at enrollment, regardless of whether progression or death had been observed. This is a stated endpoint rule; the registry record does not explain its rationale or report how many participants were affected. Without outcome estimates, analysis details, and additional missing-data information, the robustness of the primary result cannot be evaluated.

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: radiation oesophagitis (8.9%), pulmonary embolism (4.4%), general physical health deterioration (2.2%), dehydration (2.2%), leukopenia (1.1%).

The adverse-event record lists a single group titled Pemetrexed, Cisplatin, and Thoracic Radiotherapy. It reports 90 participants at risk for serious adverse events and 23 affected. For other adverse events, it reports 90 at risk and 85 affected. These figures describe the recorded group; with no separate control group, they do not provide a comparative safety estimate.

The serious adverse-event terms listed with percentages are radiation oesophagitis at 8.9%, pulmonary embolism at 4.4%, general physical health deterioration at 2.2%, dehydration at 2.2%, leukopenia at 1.1%, and hypoacusis at 1.1%. These entries identify the listed terms and percentages. The registry record does not provide further detail about event timing, duration, management, or the severity grading for each term.

The record does not report a number of deaths in the adverse-event group. It also does not state that the listed serious-event terms constitute every serious event recorded. In general, adverse-event counts describe events recorded during a study and do not, by themselves, establish that an intervention caused them. Comparative safety interpretation is especially limited without a control group and fuller event-level context.

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

The registry record establishes that a completed Phase 2, single-group study evaluated induction pemetrexed and cisplatin followed by the same drugs with concurrent thoracic radiotherapy. It defines 1-year progression-free survival as the primary outcome and describes the endpoint's censoring rules. It also records adverse-event counts and selected serious adverse-event terms.

The record does not report the observed 1-year progression-free survival percentage or its 95% confidence interval. Consequently, it does not allow readers to assess the primary outcome's estimated level or precision. Secondary outcomes are named, but their numerical results are not reported in the registry record. Naming an outcome is not the same as reporting its result.

The design also limits what the outcomes can mean. Because the study is single-group and no like-for-like control comparison is described, the observed data cannot establish how outcomes compare with another treatment. In general, results from a study group may reflect both the intervention and other factors; a comparator is needed to estimate a treatment contrast under a comparative design.

The safety counts show that serious and other adverse events were recorded in the group. The listed percentages describe selected serious-event terms, but do not by themselves show causation or relative risk. The registry record does not report the number of deaths in the adverse-event group.

Overall, the record is informative about the treatment sequence, the intended population, the endpoint definition, and the recorded safety summary. It does not provide the numerical primary efficacy result, the confidence interval, or enough comparative evidence to support claims about benefit relative to another treatment. The missing results should not be replaced by assumptions based on the study title, phase, enrollment, or endpoint definition.

14. Why This Trial Matters Statistically

This study illustrates why a registered outcome definition and a numerical outcome result serve different purposes. The record specifies what 1-year progression-free survival means, including the event definition, assessment schedule, and censoring rules. Those details help readers understand what an eventual estimate would represent. But without the observed percentage and its confidence interval, the central estimate and its precision remain unavailable.

The single-group design is also important for statistical interpretation. Describing outcomes in participants who received a regimen is not the same as estimating how those outcomes differ from a comparator. The registry record reports no like-for-like control comparison. This distinction matters whenever readers are tempted to interpret a descriptive outcome as evidence of a treatment effect.

The censoring information shows another key feature of time-to-event analysis. Participants can contribute observed follow-up even when their event status is not known through the full time point. The registry record reports 35 censored participants and specifies several circumstances that lead to censoring. These rules are central to understanding the endpoint, although the record does not report enough information to evaluate the censoring pattern or its effect on the estimate.

The safety figures likewise need context. Counts of affected participants and selected event percentages describe what was recorded in the study group, but without a comparator they do not quantify excess risk attributable to the regimen. The absent primary result, missing secondary results, and limited analysis details underline why complete numerical reporting is essential for an informed statistical assessment.

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 main limitation of the registry record for interpreting efficacy is that it does not report the observed primary endpoint value or its 95% confidence interval. Although the endpoint and its censoring rules are described, the magnitude and precision of 1-year progression-free survival cannot be assessed. Numerical results for the listed secondary outcomes are also not reported in the registry record.

The study is single-group, with allocation listed as not applicable and no like-for-like control comparison described. Therefore, the posted outcomes do not provide a randomized estimate of comparative treatment effect. This design limitation remains even if descriptive outcome values are available.

The record states that 35 participants were censored, but does not report censoring times, the number included in the primary estimate, or further information about missing observations. It describes how participants in specified circumstances were censored, including those without a complete baseline disease assessment, but does not report how many participants fell into each circumstance or sensitivity analyses.

Statistical details are limited. The registry record does not report the method used to estimate the primary outcome or its confidence interval, a statistical analysis plan, a sample-size justification, interim analyses, or a strategy for multiplicity. These omissions restrict assessment of the analysis and of uncertainty across outcomes.

The adverse-event summary provides affected counts and selected serious-event terms, but does not report the number of deaths in that record. The listed event information does not provide a comparative safety estimate or, in the available record, fuller event-level context such as timing. These limitations apply to interpretation of the posted record and should not be taken as evidence that unreported outcomes did or did not occur.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: A Study of Pemetrexed and Cisplatin, in Non Small Cell Lung Cancer — NCT01000480.
• Registry record last updated 2014-04-02; status last verified 2014-03.
• Results first posted 2014-01-01.
• 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 of pemetrexed and cisplatin as induction therapy, followed by the same drugs with concurrent thoracic radiotherapy, in unresectable, locally advanced, Stage III, nonsquamous non-small cell lung cancer. Enrollment was 90 participants. The primary outcome was 1-year progression-free survival, defined as time from enrollment to progressive disease or death from any cause.

The primary outcome's observed percentage and 95% confidence interval are not reported in the registry record. Overall survival and objective tumor response are listed as secondary outcomes, but their results are not reported. The record states that 35 participants were censored for the primary outcome and describes censoring rules.

The adverse-event summary reports 23 participants affected by serious adverse events and 85 affected by other adverse events, with 90 at risk in each category. The study has no like-for-like control comparison, limiting comparative interpretation of both efficacy and safety.