This page provides an independent statistical analysis and educational interpretation of publicly reported results. ClinicalTrials.gov provides the official trial registry record. Numerical trial results on this page are restricted to the results posted in the ClinicalTrials.gov record; calculations added by Clinical Biostats are labelled as such.
1. Trial at a Glance
This page covers the registry results for Pemetrexed Disodium With or Without Erlotinib Hydrochloride in Treating Patients With Stage IIIB-IV or Recurrent Non-Small Cell Lung Cancer (NCT00950365), a randomized phase 2 study. The primary outcome is PFS (Progression Free Survival).
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT00950365 |
| Phase | Phase 2 |
| Condition | Bronchioloalveolar Carcinoma, Large Cell Lung Carcinoma, Lung Adenocarcinoma |
| Allocation | Randomized |
| Design model | Parallel |
| Masking | None (open label) |
| Enrollment | 79 |
| Arms in the primary outcome | 2 |
| Lead sponsor | Albert Einstein College of Medicine |
| Results posted | Yes |
2. Clinical Question
Population
Patients with progressive or recurrent non-small cell lung cancer, including the stage IIIB-IV or recurrent disease described in the trial title. The registry lists several relevant conditions, including stage IIIB and stage IV non-small cell lung cancer, lung adenocarcinoma, large cell lung carcinoma, and bronchioloalveolar carcinoma. The posted record does not give a more detailed description of the analyzed population or eligibility criteria.
Intervention
Pemetrexed disodium given intravenously on day 1, together with erlotinib hydrochloride taken orally once daily on days 2-17. Courses were scheduled to repeat every 21 days, subject to disease progression or unacceptable toxicity.
Comparator
Pemetrexed disodium alone, given intravenously on day 1, with courses scheduled to repeat every 21 days in the absence of disease progression or unacceptable toxicity.
Primary question
How long participants remained alive without documented tumor progression after randomization, measured as progression-free survival (PFS), and how the reported arm-specific median times compare descriptively. The registry record reports medians and confidence intervals for each arm, but does not report a sponsor-reported comparative hazard ratio or other primary between-arm test.
3. Trial Design
This was a randomized phase II study with a parallel-arm design and no masking reported. Its official title describes a comparison of schedule-modulated concomitant pemetrexed and erlotinib against single-agent pemetrexed in patients with progressive or recurrent non-small cell lung cancer. The registry lists an enrollment of 79 and a completed status. It identifies Albert Einstein College of Medicine as the sponsor.
Arm A received pemetrexed disodium intravenously over 10 minutes on day 1. Arm B received pemetrexed as in Arm A and erlotinib hydrochloride orally once daily on days 2-17. In both arms, courses repeated every 21 days unless disease progression or unacceptable toxicity occurred. The registry also lists laboratory biomarker analysis as an intervention, but does not report a biomarker result in the outcome information.
The primary outcome was PFS, defined as time from randomization until documented tumor progression or death from any cause, assessed up to 12 months. The record defines progression using RECIST v1.0: a 20% increase in the sum of the longest diameter of target lesions, a measurable increase in a non-target lesion, or new lesions. Secondary outcomes named in the record include objective response rate and overall survival. Detailed posted results are available for objective response rate; an overall survival result is not reported in the registry record.
The endpoint summaries use 25.0 participants in Arm A and 50.0 in Arm B, while overall enrollment is listed as 79. The registry record does not explain the difference between the enrollment figure and the arm counts in these summaries. It also does not report further details of the randomization procedure or the analysis population.
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
| Stage | Arm A (Pemetrexed) | Arm B (Pemetrexed Disodium, Erlotinib Hydrochloride) |
|---|---|---|
| STARTED | 27 | 52 |
| COMPLETED | 25 | 50 |
| NOT COMPLETED | 2 | 2 |
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.
| Characteristic | Unit | Arm A (Pemetrexed) | Arm B (Pemetrexed Disodium, Erlotinib Hydrochloride) | Total |
|---|---|---|---|---|
| Participants analysed | 27 | 52 | 79 | |
| Age, Continuous | years | 64 (47 to 91) | 62 (37 to 86) | 63 (37 to 91) |
| Sex: Female, Male: Female | Participants | 13 | 29 | 42 |
| Sex: Female, Male: Male | Participants | 14 | 23 | 37 |
| Race/Ethnicity, Customized: White | participants | 18 | 36 | 54 |
| Race/Ethnicity, Customized: Black | participants | 5 | 9 | 14 |
| Race/Ethnicity, Customized: Hispanic | participants | 4 | 6 | 10 |
| Race/Ethnicity, Customized: Asian | participants | 0 | 2 | 2 |
| Smoking history: <=15 pack-years | participants | 5 | 17 | 22 |
| Smoking history: >15 pack-years | participants | 22 | 35 | 58 |
| ECOG PS: ECOG PS 0 | participants | 24 | 46 | 70 |
| ECOG PS: ECOG PS 1/2 | participants | 3 | 6 | 9 |
| Histology: Nonsquamous: Prior platinum-containing chemotherapy | participants | 27 | 50 | 77 |
| Histology: Nonsquamous: Prior antiangiogenic inhibitor | participants | 10 | 18 | 28 |
| Evaluable patients with atleast one source of biospecimen: Archival tumor specimens | participants | 6 | 14 | 20 |
| Evaluable patients with atleast one source of biospecimen: Collected blood samples | participants | 17 | 32 | 49 |
| Evaluable patients with atleast one source of biospecimen: EGFR (epidermal growth factor receptor) wild type | participants | 21 | 31 | 52 |
| Evaluable patients with atleast one source of biospecimen: EGFR (epidermal growth factor receptor) mutations | participants | 0 | 7 | 7 |
| Evaluable patients with atleast one source of biospecimen: Unkown EGFR (epidermal growth factor recep) status | participants | 4 | 12 | 16 |
6. Primary Endpoint
The registry lists the primary outcome as PFS (Progression Free Survival), measured over Time from randomization until documented tumor progression or death from any cause, assessed up to 12 months.
| Element | Registry entry |
|---|---|
| Result type | Median |
| Measure of spread | 95% Confidence Interval |
| Unit | months |
| Endpoint classification | Time-to-Event Analysis |
PFS is a time-to-event endpoint. For each participant, it measures the time from randomization until the first of documented tumor progression or death from any cause. Counting death as an event means the endpoint captures more than tumor growth alone. The record describes progression according to RECIST v1.0 and states that PFS was assessed up to 12 months.
The reported summary is the median PFS in each arm, with a 95% confidence interval. The median is the time by which half of the participants in the relevant group are estimated to have experienced progression or death, and half have not yet experienced either event. It can summarize follow-up even when not every participant has an observed event, although the exact estimation and censoring procedures are not reported in the registry record.
Time-to-event outcomes are commonly used when the timing of an event matters and participants may have different lengths of follow-up. In general, a median gives a useful description of the event-time distribution, while a comparative hazard ratio can summarize relative event rates over follow-up under its modeling assumptions. The registry record gives arm-specific median estimates but does not report a sponsor-reported hazard ratio for the primary endpoint. The medians therefore describe each arm; by themselves they do not supply a formal adjusted or unadjusted test of the treatment contrast.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The posted primary results report median PFS of 8.0 months in Arm A, with a 95% confidence interval from 0.0 to 19.0 months, and 20.0 months in Arm B, with a 95% confidence interval from 7.0 to 29.0 months. These are arm-specific estimates. The interval around each estimate indicates uncertainty, and both intervals are broad. The registry record does not report a sponsor-reported hazard ratio, confidence interval for a comparative hazard ratio, or p-value for the primary PFS comparison.
The two medians are numerically different, but that descriptive contrast is not enough to establish the size or precision of a treatment effect. A difference between medians cannot be treated as a hazard ratio, and no new comparative value should be inferred from these summaries. The record also does not report the numbers of progression or death events, the follow-up distribution, or the method used to estimate the medians. Those details would help readers assess how much information supports the time-to-event estimates.
The registry reports objective response rates of 12.0% in Arm A and 28.0% in Arm B, each with a 95% confidence interval. A separate unadjusted recalculation gives a risk difference of 0.16, with a confidence interval from -0.018 to 0.338 and p = 0.119. This recalculation is not a sponsor-reported analysis. Its interval includes values on either side of no difference, so the recalculation is imprecise about the direction and size of the response-rate contrast. The registry record does not list a reported analysis for this secondary outcome.
The primary and secondary summaries should not be read as interchangeable evidence. PFS concerns time to progression or death; objective response concerns tumor response under RECIST. A response-rate result does not by itself establish a PFS effect, and the record does not report an overall survival result. The planned sample-size illustrations associated with the response-rate recalculation are hypothetical planning scenarios based on the observed effect, not evidence about the power of this completed trial.
These results describe the posted record rather than establish a clinical conclusion. The available summaries leave important questions about comparative analysis, event counts, missing observations, and analysis populations unanswered. Without those details, the arm-specific estimates can be reported accurately, but the registry information does not support a more complete account of the primary treatment comparison.
9. Statistical Methods Explained
Several statistical ideas help interpret these results, but the distinction between reported analysis and general explanation is important. The registry record reports arm-specific median PFS values with 95% confidence intervals. It does not report a sponsor-reported comparative hazard ratio or a test of the primary PFS contrast. General statistical concepts below explain what such summaries mean; they should not be taken as descriptions of methods that the trial necessarily used.
What does a confidence interval express?
In general, a confidence interval expresses uncertainty around an estimate under the assumptions of the method used to construct it. A narrower interval indicates greater precision than a wider interval, all else being comparable. The PFS intervals are broad: Arm A is reported as 8.0 months with an interval from 0.0 to 19.0, and Arm B as 20.0 months with an interval from 7.0 to 29.0. The endpoints show that the median estimates are not precise. A confidence interval is not a guarantee that the true value lies within that particular interval, and it does not by itself test whether arms differ.
For a between-arm question, an interval around a comparative measure is generally more directly informative than separate arm-specific intervals. For time-to-event data, a hazard ratio is one common comparative measure. It compares event rates over time under a model and assumptions; it is not the ratio of the two medians. The registry record does not report a sponsor-reported primary hazard ratio or its confidence interval. No such comparison can be reconstructed from the posted medians alone.
Why does censoring matter for PFS?
General explanation: time-to-event analyses can include participants whose event has not been observed by the end of their available follow-up. Their observation time is usually treated as censored at the last time they are known to be event-free. This allows their observed time to contribute without pretending that they had an event or that they remained event-free indefinitely. The handling of censoring, loss to follow-up, and other incomplete observations can affect estimates. The registry record does not describe these procedures or report the numbers censored.
For PFS, the event is the first documented progression or death from any cause. The registry definition specifies RECIST v1.0 criteria for progression and states that the outcome was assessed up to 12 months. It does not report the event counts, dates of assessment, or details about how progression was confirmed. These omissions limit assessment of the underlying event-time data.
What do the secondary response statistics say?
The registry reports objective response rates of 12.0% in the pemetrexed arm and 28.0% in the combination arm, with 95% confidence intervals. An unadjusted recalculation from the posted summary statistics gives a risk difference of 0.16, with a 95% confidence interval from -0.018 to 0.338, and p = 0.119. This is explicitly a recalculated summary, rather than a sponsor-reported analysis. Since the discrepancy indicator is false, there is no flagged disagreement requiring a sponsor analysis to take precedence; nevertheless, the recalculation remains unadjusted and should not be mistaken for the trial's full analysis.
In general, a risk difference describes the contrast in event probabilities between groups on an absolute scale. A confidence interval that includes zero is compatible with no difference as well as with differences in either direction under the calculation's assumptions. The p-value is a measure of how unusual the observed data would be under a specified null model; it is not the probability that the null hypothesis is true and does not measure clinical importance. The registry record does not report a multiplicity-adjusted analysis for this outcome.
How should the sample-size illustrations be read?
The planning illustrations are based on the observed response effect and state assumptions of a two-sided significance level of 0.05, equal allocation, and a normal approximation. They give participants per arm for 80% power and participants per arm for 90% power under scenarios using 100%, 75%, and 50% of the observed effect. They are planning illustrations, not the trial's observed power and not evidence that the trial was designed around those assumptions. The registry record does not report the original sample-size justification, target effect, or design assumptions.
General explanation: planning calculations depend on the effect size chosen, the variability or event probability, the error rate, allocation, and analysis method. Smaller assumed effects generally require larger samples to achieve the same target power, all else equal. These illustrations show how hypothetical choices affect planning; they do not change the uncertainty in the results already observed.
What methods remain undocumented?
The registry record does not report the statistical model for PFS, covariate adjustment, stratification factors, censoring rules, analysis population, missing-data approach, or whether interim analyses were planned or conducted. It reports no sponsor-reported analyses in the secondary analysis listing. These absences do not establish that no such procedures existed; they mean the methods are not reported in the registry record. Readers should therefore distinguish the descriptive summaries and recalculated response comparison from any more comprehensive analysis that may have been conducted elsewhere.
10. Multiplicity, Missing Data and Analysis Populations
The registry record lists PFS as the primary outcome and identifies objective response rate and overall survival among the secondary outcomes. It does not report a multiplicity-adjustment plan, a hierarchy for testing outcomes, or an account of which analyses were prespecified. No interim analysis information is reported in the registry record. These gaps make it difficult to determine how the reported outcomes fit into a broader inferential plan or whether any results were selected for emphasis after examination.
In general, multiplicity refers to the added risk of false-positive findings when several hypotheses or outcomes are tested. Prespecified testing strategies can manage that risk by defining which comparisons are confirmatory and how statistical error is controlled. Without a reported strategy, the secondary response comparison is best treated as an unadjusted, supplementary result. The registry record does not report a sponsor analysis for that comparison, and the recalculation should not be confused with an adjusted confirmatory test.
The registry reports 79 participants enrolled, while the posted endpoint summaries use 25.0 participants in Arm A and 50.0 in Arm B. The record does not explain this difference or state whether these arm counts represent all randomized participants, participants with available outcome data, or another analysis population. It also does not report how missing outcome data were handled, how many participants were censored for PFS, or how many participants were excluded from any analysis.
In general, missingness and analysis-population definitions matter because exclusions or incomplete follow-up can affect the balance created by randomization and the precision or interpretation of estimates. This is not evidence that such problems occurred in this trial; it is a limit on what can be assessed from the record. The methods for randomization, allocation concealment, endpoint adjudication, and analysis are not reported in the registry record. The completed status and listed outcome summaries do not fill in those methodological details.
11. Safety Results
The registry reports serious adverse events as affected participants divided by participants at risk.
| Arm | Participants with serious adverse events | Participants at risk | Percentage |
|---|---|---|---|
| Arm A (Pemetrexed) | 9 | 25 | 36.0% |
| Arm B (Pemetrexed Disodium, Erlotinib Hydrochloride) | 16 | 50 | 32.0% |
Deaths
| Arm | Deaths (participants affected of at risk) |
|---|---|
| Arm A (Pemetrexed) | 0 of 25 |
| Arm B (Pemetrexed Disodium, Erlotinib Hydrochloride) | 0 of 50 |
Other (non-serious) adverse events
Participants with at least one non-serious event at or above the registry's 0% reporting threshold.
| Arm | Participants affected of at risk |
|---|---|
| Arm A (Pemetrexed) | 25 of 25 |
| Arm B (Pemetrexed Disodium, Erlotinib Hydrochloride) | 50 of 50 |
Most frequent serious adverse event terms
| Event term | Organ system | Arm A (Pemetrexed) | Arm B (Pemetrexed Disodium, Erlotinib Hydrochloride) |
|---|---|---|---|
| Thrombocytopenia | Blood and lymphatic system disorders | 7 of 25 | 10 of 50 |
| Neutropenia | Blood and lymphatic system disorders | 2 of 25 | 5 of 50 |
| Insterstitial lung disease | Respiratory, thoracic and mediastinal disorders | 0 of 25 | 1 of 50 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Arm A (Pemetrexed) | Arm B (Pemetrexed Disodium, Erlotinib Hydrochloride) |
|---|---|---|---|
| Anemia | Blood and lymphatic system disorders | 14 of 25 | 33 of 50 |
| Rash | Skin and subcutaneous tissue disorders | 7 of 25 | 35 of 50 |
| Diarrhea | Gastrointestinal disorders | 3 of 25 | 23 of 50 |
| Nausea | Gastrointestinal disorders | 4 of 25 | 20 of 50 |
| Anorexia | Metabolism and nutrition disorders | 4 of 25 | 17 of 50 |
| Hyperglycemia | Metabolism and nutrition disorders | 5 of 25 | 15 of 50 |
| Dry skin | Skin and subcutaneous tissue disorders | 4 of 25 | 13 of 50 |
| Vomiting | Gastrointestinal disorders | 2 of 25 | 13 of 50 |
| Transaminases | Endocrine disorders | 3 of 25 | 9 of 50 |
| Dehydration | General disorders | 3 of 25 | 7 of 50 |
Serious events with the highest arm-level rate: thrombocytopenia (28.0%), neutropenia (10.0%), insterstitial lung disease (2.0%).
The registry reports serious adverse events affecting 9 of 25 participants at risk in Arm A and 16 of 50 participants at risk in Arm B. It reports other adverse events affecting 25 of 25 participants at risk in Arm A and 50 of 50 participants at risk in Arm B. The record lists zero deaths in each arm in its adverse-event summary. These counts describe the posted safety summaries; the registry record does not provide a comparative statistical analysis of adverse events.
The listed serious adverse-event terms and percentages are thrombocytopenia, 28.0%; neutropenia, 10.0%; and interstitial lung disease, 2.0%. The record does not clarify in this summary whether each listed percentage is specific to an arm or pooled across arms, so these percentages should not be assigned to an individual arm.
In general, adverse-event counts should be interpreted in light of how events were defined, collected, and attributed, and of participants' time under observation. The registry record does not report those details here, nor does it give a fuller breakdown by severity, timing, or treatment relationship. The counts alone do not establish that one regimen caused more or fewer events than the other.
12. What the Result Does, and Does Not, Mean
The results establish what the registry record reports: a randomized phase II comparison of pemetrexed alone with pemetrexed plus erlotinib, arm-specific median PFS estimates with confidence intervals, and an objective response outcome. The median PFS estimates were 8.0 months for Arm A and 20.0 months for Arm B. Their confidence intervals are broad, and the registry record does not report a sponsor-reported comparative hazard ratio or primary p-value. The response-rate figures and their unadjusted recalculation are supplementary, not a replacement for that missing primary comparison.
These summaries do not establish the magnitude or precision of a treatment effect on PFS. A difference between the two medians is not a hazard ratio, and the registry record does not provide enough comparative information to characterize the time-to-event contrast fully. The record also does not report an overall survival result. Consequently, the posted information cannot describe whether the PFS pattern is accompanied by a particular overall survival pattern.
In general, a randomized design is intended to support a fair comparison between assigned groups, but interpretation still depends on how participants were analyzed, how outcomes and censoring were handled, and what comparative statistics were estimated. The registry record does not report these details sufficiently to assess them. This does not show that the methods were inadequate; it means they are not available in this record.
The response-rate recalculation is unadjusted and imprecise, and the record does not report a multiplicity plan. The sample-size illustrations are hypothetical planning scenarios based on the observed response effect, not a measure of the trial's observed power. None of these results should be converted into a claim that either regimen works or does not work. They are statistical descriptions of the posted outcomes, with important limits on comparative interpretation.
13. Why This Trial Matters Statistically
This trial is statistically informative as an example of why arm-specific summaries and comparative analyses answer different questions. The registry reports a median PFS and confidence interval for each arm, but not a sponsor-reported comparative hazard ratio or primary test. Readers can describe the estimates as posted, while recognizing that the direct treatment contrast remains incompletely characterized in the registry record.
The endpoint also illustrates the importance of distinguishing a time-to-event outcome from a binary outcome. PFS combines the timing of progression or death, whereas objective response rate records response status under RECIST. Those outcomes can provide complementary perspectives, but a result for one does not determine the result for the other. Here, the response comparison is available only as an unadjusted recalculation, and an overall survival result is not reported in the registry record.
The planning illustrations highlight another statistical distinction: a hypothetical sample-size calculation is not evidence of the power achieved by a completed study. The calculations are framed around fractions of the observed response effect and stated assumptions. They can illustrate how planning choices influence sample requirements, but they cannot recover the original design rationale, which is not reported in the registry record.
Finally, the gap between listed enrollment and arm counts used in endpoint summaries underscores why analysis populations and missing-data accounting matter. The record does not explain the gap, and no explanation should be inferred. Clear reporting of participant flow, event counts, methods, and comparative estimates would make the statistical evidence easier to evaluate. As posted, this study supports careful descriptive reading while leaving central inferential details unresolved.
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.
Several limitations are specific to the information posted for this trial. The registry gives arm-specific median PFS estimates but does not report the sponsor's comparative hazard ratio, a confidence interval for that comparison, or a primary p-value. It also does not give the numbers of progression or death events, censoring counts, or details of follow-up beyond the stated assessment up to 12 months. The medians can therefore be described, but the relative time-to-event effect cannot be fully assessed from the record.
The endpoint summaries use 25.0 participants in Arm A and 50.0 in Arm B, while the record lists enrollment of 79. It does not explain the difference or define the populations represented by those arm counts. There is no participant-flow description or reported accounting of missing outcome data. These omissions prevent assessment of whether all enrolled participants contributed to each endpoint summary.
The registry describes the progression criteria but does not report how the endpoint was analyzed, how censoring was handled, or whether the analysis adjusted for prognostic factors. The randomization procedure and allocation concealment are not described. The record also does not report a multiplicity plan, interim-analysis information, or the original sample-size justification.
For secondary outcomes, objective response has posted arm-specific values and a recalculated unadjusted comparison, but no reported sponsor analysis. Overall survival is named as an outcome without a posted result in the registry record. The adverse-event summary gives affected counts and selected terms, but does not clarify the arm attribution of the listed term percentages or supply fuller event detail. These are limitations of the registry record and should not be treated as proof that the underlying trial lacked additional analyses or documentation.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Pemetrexed Disodium With or Without Erlotinib Hydrochloride in Treating Patients With Stage IIIB-IV or Recurrent Non-Small Cell Lung Cancer — NCT00950365.
- Registry record last updated 2020-09-16; status last verified 2020-08.
- Results first posted 2020-09-16.
- 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.
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18. Record Summary
The registry identifies NCT00950365 as a completed randomized phase II parallel-group study sponsored by Albert Einstein College of Medicine. It compared pemetrexed disodium alone with pemetrexed plus erlotinib hydrochloride in patients with progressive or recurrent non-small cell lung cancer. The record lists enrollment of 79 and reports no masking.
The primary outcome was PFS, defined from randomization to documented progression or death from any cause, assessed up to 12 months. Median PFS was 8.0 months in Arm A and 20.0 months in Arm B, with broad 95% confidence intervals. A sponsor-reported comparative primary analysis is not reported in the registry record. Objective response rate is also posted, with a separate unadjusted recalculation; an overall survival result is not reported in the registry record.
The registry does not explain why the endpoint summaries use 25.0 participants in Arm A and 50.0 in Arm B, or report key analysis details such as censoring, missing-data handling, analysis populations, and multiplicity procedures. The available results therefore permit descriptive summaries but leave important aspects of the comparative statistical interpretation unresolved.