Selumetinib and Erlotinib Hydrochloride in Treating Patients With Locally Advanced or Metastatic Pancreatic Cancer: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Selumetinib and Erlotinib Hydrochloride in Treating Patients With Locally Advanced or Metastatic Pancreatic Cancer (NCT01222689), a na phase 2 study. The primary outcome is Overall Survival (OS).

2. Clinical Question

In plain terms, the study asks how long patients in this treatment group lived after receiving the combination, as captured by the trial’s overall-survival analysis. It does not directly compare the combination with another treatment or with a control group. That distinction matters: a single-group survival estimate describes outcomes among enrolled patients, but cannot by itself separate treatment effects from other influences on survival, such as patients’ clinical characteristics, prior treatment, or the course of the disease.

The record lists a phase II study sponsored by the National Cancer Institute. It describes the treatment as intended for advanced pancreatic adenocarcinoma after chemotherapy and includes locally advanced or metastatic disease in the brief summary. The listed secondary outcomes cover progression-free survival, CA19-9 biomarker response, objective radiographic response by RECIST criteria, toxicities, and dose modifications. Those outcomes address different aspects of disease course and treatment experience; none is a substitute for the primary overall-survival endpoint.

The registry record does not report a numerical median overall-survival estimate or its confidence interval. Therefore, it supports describing the study question and planned measurement, but not a conclusion about the observed survival time or the effect of treatment relative to an alternative.

3. Trial Design

This is a phase II, single-group study of selumetinib plus erlotinib hydrochloride for second-line treatment of advanced pancreatic adenocarcinoma. The registry reports enrollment of 46. It lists one treatment group, and the allocation field is not applicable. With no concurrent comparison group, the study is not a randomized comparison of the combination against another regimen, placebo, or usual care.

The treatment description specifies selumetinib and erlotinib hydrochloride by mouth once daily on days 1–21, with courses repeating every 21 days. Treatment continues in the absence of disease progression or unacceptable toxicity. The registry also lists laboratory biomarker analysis as an intervention. Masking is recorded as none. The record identifies the study as completed, with start recorded as 2010-11 and primary completion as 2013-04.

The intended population is described as patients with locally advanced or metastatic pancreatic cancer refractory to chemotherapy. The official title characterizes the study as second-line treatment of advanced pancreatic adenocarcinoma. The conditions list includes adenocarcinoma of the pancreas, recurrent pancreatic cancer, and stage III and stage IV pancreatic cancer. These descriptions identify the clinical setting but do not provide detailed eligibility criteria or a breakdown of enrolled patients by disease stage or prior treatment.

Overall survival is the primary endpoint, with a timeframe of up to 2 years. Secondary outcomes include progression-free survival, CA19-9 biomarker response, objective radiographic response by RECIST criteria, incidence of graded toxicities, and dose modifications and their reasons. The registry record does not report a detailed statistical analysis plan, the criteria for analysis populations, or how missing outcome data were handled.

Because the design has one group, the results can describe outcomes in the enrolled group but do not provide a like-for-like treatment contrast. Any interpretation as a treatment effect would require evidence beyond the within-group observations, such as a suitable controlled comparison; such a comparison is not part of this study design.

4. Participant Flow and Accounting

The registry reports how participants moved through each stage of the study. All counts below are exactly as posted; missing counts are not inferred from other stages.

Overall Study

5. Baseline Characteristics

The table reproduces the baseline characteristics posted in the registry, which describe the participants analysed at baseline and help show whether the randomized groups were comparable.

6. Primary Endpoint

The registry lists the primary outcome as Overall Survival (OS), measured over Up to 2 years.

Overall survival is the time from a defined starting point to death from any cause. It is a time-to-event endpoint: each participant contributes information about survival time, or about the period during which they were observed without a recorded death. The registry identifies the primary summary as median overall survival in months and states that survival will be calculated using the Kaplan–Meier method.

The median is the point in the estimated survival distribution at which the estimated probability of remaining alive reaches one half. It offers an interpretable summary of survival experience without requiring every participant to have died during observation. The registry also describes calculating actual and estimated probabilities of being alive at 24 weeks (6 months) and at other multiples of 6 months when the number of uncensored subjects is not smaller than 10. These time-specific estimates complement the median by describing survival at selected follow-up points.

Overall survival is commonly used in clinical trials because it captures a direct, clinically meaningful event and does not depend on subjective assessment of tumor change. Its interpretation still depends on follow-up, censoring, and the population studied. Censoring occurs when a participant’s survival time is not fully observed during the relevant follow-up; the Kaplan–Meier method accounts for such incomplete observation under assumptions about censoring.

The registry specifies a 95% confidence interval for the median. A confidence interval expresses statistical uncertainty around an estimate; it does not remove uncertainty about whether results apply to other patients. The registry record does not report the median estimate or its confidence interval, so the observed survival result cannot be described from this record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

What does the Kaplan–Meier method estimate?

The Kaplan–Meier method estimates the probability of remaining alive over time while allowing participants to have different lengths of follow-up. Participants who have a recorded death contribute an event time. Participants whose observation ends before a death is recorded are censored at the end of their observed follow-up. Censoring does not mean that a participant is known to have survived beyond that point; it means the analysis does not observe what happened afterward.

In general, the method uses the observed event times and the participants still under observation at those times to form a stepwise survival curve. The registry describes calculating both actual and estimated probabilities of being alive at 24 weeks (6 months) and at multiples of 6 months when the number of uncensored subjects is not smaller than 10. This criterion indicates that the planned time-specific reporting was conditional on how much uncensored follow-up information remained. The record does not provide those probability estimates or the underlying survival curve.

What does the median represent?

The median overall-survival time is read from the estimated survival curve at the point where the estimated probability of being alive reaches one half. It condenses the survival distribution into one time value, but it does not describe every participant’s experience or the shape of the full curve. Two studies could have the same median while having different survival patterns at other times. The registry specifies the median in months as the primary summary, but does not report its numerical value.

A 95% confidence interval gives a range of values compatible with the data under the statistical method and its assumptions. In general, it conveys sampling uncertainty around the estimated median. It does not mean there is a 95% probability that the fixed true value lies within the particular calculated interval, and it does not address every source of bias or uncertainty. The registry record does not give the interval endpoints.

Why does censoring matter?

Time-to-event analyses can include participants whose event has not been observed by the end of follow-up, rather than treating their incomplete observation as if it were a completed survival time. The interpretation relies on assumptions about censoring, including that the censoring process does not systematically conceal a different event risk in a way that distorts the estimate. The registry record does not describe censoring patterns or provide diagnostic information that would permit assessment of those assumptions.

Follow-up is specified as up to 2 years. That limit describes the stated timeframe, not necessarily equal observation time for every participant. The record does not report follow-up completeness or how many participants were observed at each time point. Therefore, the precision of later survival estimates cannot be assessed from the information.

What can a single-group estimate establish?

A single-group estimate describes the outcome distribution among people who entered the study and were followed under its treatment regimen. It does not create the counterfactual comparison needed to determine what would have happened to those same people under another treatment. In general, randomization helps balance known and unknown prognostic factors between groups, while a concurrent control also helps distinguish treatment-related changes from background disease course and changes in care. This trial has neither a randomized allocation nor a separate comparison group, so its design cannot estimate a randomized between-group effect.

That limitation does not make descriptive estimation meaningless. It does mean the estimate must be interpreted as an outcome observed in this study group rather than as proof that the regimen caused a particular survival result. Here, the registry does not report the numerical primary estimate, further limiting what can be inferred.

How should planning illustrations be read?

The registry describes planning illustrations based on an observed effect, with a two-sided significance level of 0.05, equal allocation between two hypothetical arms, and a normal approximation. The effect to detect is specified as a fraction of the observed effect. For time-to-event planning, the stated quantity is the total number of events under the Schoenfeld approach; other planning quantities are participants per arm. These assumptions describe illustrations, not the design of this single-group trial. They are not observed power, and they should not be confused with the number enrolled or with an outcome result.

In general, a sample-size calculation asks what scale of study might be needed to detect a specified effect under chosen assumptions. It does not show that the effect exists, and a post hoc calculation using an observed effect can be particularly dependent on that estimate. No numerical planning values are reported in the record information available for this analysis, and the trial’s own sample-size justification is not reported in the registry record.

What do the secondary outcomes add?

Progression-free survival tracks time until disease progression or death, according to the endpoint’s specified definition. Objective radiographic response by RECIST criteria concerns tumor response assessed using defined imaging criteria. The CA19-9 outcome is described as a response defined by a 50% decline from baseline among patients with a baseline measurement greater than 2 x ULN. Toxicity and dose-modification outcomes capture safety and treatment delivery. These endpoints answer different questions and may have different analysis populations, follow-up, and missing-data issues. Their numerical results and detailed analysis methods are not reported in the registry record.

10. Multiplicity, Missing Data and Analysis Populations

The registry lists overall survival as the primary outcome and several secondary outcomes: progression-free survival, CA19-9 biomarker response, objective radiographic response by RECIST criteria, toxicity incidence, and dose modifications with reasons. Testing or estimating multiple outcomes raises a multiplicity issue. In general, the more outcomes assessed, the greater the chance that at least one apparently notable result may arise by chance when many statistical tests are performed. A prespecified hierarchy, adjustment procedure, or clear distinction between confirmatory and exploratory analyses can help readers interpret multiple findings.

The registry record does not report a multiplicity strategy, a hierarchy among the secondary outcomes, or a detailed statistical analysis plan. It therefore does not establish whether any adjustment was planned for multiple comparisons or how outcomes were prioritized beyond naming overall survival as primary. Without reported analysis details and outcome estimates, the strength of evidence for secondary outcomes cannot be assessed.

Missing data and censoring also affect interpretation. For overall survival, the registry describes Kaplan–Meier estimation, which can accommodate censoring when its assumptions are suitable. The record does not report the number censored, the amount of follow-up, reasons for loss to follow-up, or sensitivity analyses addressing informative censoring. For other outcomes, the record does not specify how missing measurements, unevaluable scans, or incomplete biomarker data were handled.

The analysis populations are not described in detail. The record does not state which participants were included in each endpoint analysis or how protocol deviations and treatment discontinuation affected inclusion. These omissions do not establish that analyses were inappropriate; they mean that the registry record does not provide enough information to evaluate those choices. The reported enrollment is 46, but the record does not state endpoint-specific denominators or present numerical efficacy results in the information recorded for the trial.

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 0% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: fatigue (23.9%), neoplasms benign, malignant and unspecified (incl cysts and polyps) - other, specify - disease progr (15.2%), vomiting (8.7%), dehydration (8.7%), acites (6.5%).

The registry safety summary lists one treatment group. It reports 46 participants at risk and 22 affected in the serious adverse-event summary, and 46 at risk and 46 affected in the other adverse-event summary. These are group-level counts as recorded; they are not a comparison between treatment arms. The record lists fatigue at 23.9%, disease progression under a neoplasms category at 15.2%, vomiting at 8.7%, dehydration at 8.7%, ascites at 6.5%, and nausea at 6.5% among the top serious-event terms.

These percentages identify reported event terms, but the registry summary does not give details such as event timing, duration, severity distribution, or whether an event was judged related to the study drugs. A listed serious event is not automatically caused by treatment. Disease progression may also be recorded among serious events, but its listing does not make it a drug toxicity. The registry separately identifies toxicity grading using the National Cancer Institute Common Terminology Criteria for Adverse Events Version 4.0 as a secondary outcome; the numerical grading details are not reported in the registry record.

Safety summaries are descriptive and should be interpreted in the context of the study’s single treatment group and follow-up. They do not establish comparative safety against another regimen. The record does not report a separate control group, so these counts and percentages cannot show whether event occurrence was higher or lower than under an alternative treatment.

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

This study asks about overall survival among patients receiving selumetinib and erlotinib hydrochloride as second-line treatment for advanced pancreatic adenocarcinoma. It is a phase II study with one treatment group, enrollment of 46, and a specified Kaplan–Meier approach to the primary endpoint. Those details identify the clinical question and intended outcome measurement.

The registry record does not report the numerical median overall-survival result or its 95% confidence interval. It therefore does not show the magnitude or precision of the primary survival estimate. The record also does not provide numerical findings for the listed secondary outcomes in the information available for this trial. Without those results, no claim about the observed survival, tumor response, biomarker change, or progression-free survival can be made from this record.

Even if a within-group survival result were available, the design would limit causal interpretation. A single-group study can describe what happened among enrolled participants, but it cannot establish how those outcomes compare with what would have happened under a different treatment. The absence of randomization and a concurrent comparator means that participant characteristics, disease severity, prior treatment, and other aspects of care could contribute to observed outcomes. This is a design limitation, not a numerical adjustment that can be resolved from the listed group alone.

The listed safety figures describe reported events in the treatment group, including serious-event counts and selected event percentages. They do not establish that the regimen caused those events, and they do not offer a comparative safety estimate. The registry record does not provide enough detail to assess event attribution, timing, or all aspects of severity.

Accordingly, the record supports a description of the trial’s design, planned endpoint, treatment schedule, and selected safety summaries. It does not support a quantitative conclusion about survival benefit or comparative effectiveness. The record’s lack of reported efficacy estimates should be distinguished from a finding of no effect: an unreported result is not evidence that an outcome was absent or unchanged.

13. Why This Trial Matters Statistically

This trial is statistically informative as an example of the distinction between measuring an outcome and estimating a treatment effect. Overall survival is a time-to-event endpoint, and the registry specifies a Kaplan–Meier method, a median summary, and a 95% confidence interval. Those choices indicate how the primary outcome was intended to be described. Yet statistical methods cannot compensate for the absence of a reported numerical result in the registry record.

The single-group design is central to interpretation. It permits description of survival and safety within the treatment group, but it does not provide a concurrent control against which to estimate a treatment contrast. This makes it important to avoid reading any within-group outcome as though it were a randomized comparison. In a disease setting described as advanced and refractory to chemotherapy, the context of prior treatment and disease course is especially relevant to interpreting outcomes, though the record does not provide detailed patient characteristics.

The registry also illustrates why endpoint-specific information matters. Overall survival, progression-free survival, radiographic response, biomarker response, toxicity, and dose modification capture different questions. Each can involve different definitions, observation windows, and missingness. Simply listing these outcomes does not disclose their results or analytical details. Reporting those details would be necessary for readers to assess the estimates and their precision.

The planning assumptions also need to be separated from the actual study design. Illustrations based on an observed effect and hypothetical equal allocation between two arms are not a description of this single-group trial, nor are they observed power. This distinction helps prevent planning calculations from being mistaken for evidence about an outcome. The main statistical contribution of the registry record is therefore its specification of the trial question and analysis framework, alongside clear limits on what can be concluded from the results it reports.

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 interpreting this trial from its registry record. The most direct is that the primary endpoint is identified, but its numerical median overall-survival result and 95% confidence interval are not reported. The record also does not report a numerical hazard ratio or numerical results for the listed secondary outcomes. Without endpoint estimates, their precision and clinical context cannot be evaluated.

The study has a single treatment group, with allocation recorded as not applicable and masking recorded as none. There is no concurrent control group for a like-for-like comparison. This design limits causal conclusions, because outcomes observed in the treatment group cannot distinguish the regimen’s contribution from other influences on survival, disease progression, response, or adverse events.

The registry record does not report detailed eligibility criteria, participant characteristics, endpoint-specific analysis populations, or the number included in each outcome analysis. It also does not describe follow-up completeness, censoring patterns, missing-data methods, or sensitivity analyses. These omissions make it difficult to assess representativeness and the robustness of endpoint estimates, even if estimates were available elsewhere.

The record lists several secondary outcomes but does not describe a multiplicity strategy or a detailed statistical analysis plan. It does not report whether outcome definitions or analyses changed over time. The registry does not provide the trial’s sample-size justification, interim-analysis plan, or a detailed explanation of how protocol deviations were addressed. Each of these items is not reported in the registry record and should not be inferred from the phase designation or enrollment.

Safety information is also limited to the recorded group summaries and selected event terms. The registry does not provide event-level timing, attribution, or a complete account of severity and duration in the information recorded. These limitations call for cautious descriptive interpretation rather than a comparative claim.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Selumetinib and Erlotinib Hydrochloride in Treating Patients With Locally Advanced or Metastatic Pancreatic Cancer — NCT01222689.
• Registry record last updated 2020-07-31; status last verified 2020-07.
• Results first posted 2016-11-07.
• 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

The registry record describes NCT01222689, a completed phase II study sponsored by the National Cancer Institute. It enrolled 46 and evaluated selumetinib with erlotinib hydrochloride in a single treatment group for second-line treatment of advanced pancreatic adenocarcinoma. The treatment description specifies oral once-daily dosing on days 1–21, with 21-day courses repeated in the absence of progression or unacceptable toxicity.

Overall survival was the primary outcome, planned as a median in months using the Kaplan–Meier method, with a 95% confidence interval and follow-up up to 2 years. Secondary outcomes included progression-free survival, CA19-9 response, radiographic response, toxicity, and dose modifications. The record does not report the numerical primary survival estimate or its confidence interval, nor numerical results for the listed secondary outcomes. The single-group design does not provide a randomized comparison, so the registry record supports description of the study and its planned measurements rather than a comparative treatment-effect conclusion.