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 Pembrolizumab and Concurrent Chemoradiotherapy or Radiation Therapy in Treating Patients With Small Cell Lung Cancer (NCT02402920), a non-randomized phase 1 study. The primary outcome is Dose Limiting Toxicity (DLT).
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT02402920 |
| Phase | Phase 1 |
| Condition | Extensive Stage Small Cell Lung Carcinoma, Limited Stage Small Cell Lung Carcinoma, Neuroendocrine Neoplasm |
| Allocation | Non-Randomized |
| Design model | Parallel |
| Masking | None (open label) |
| Enrollment | 83 |
| Arms in the primary outcome | n/a |
| Lead sponsor | M.D. Anderson Cancer Center |
| Results posted | Yes |
2. Clinical Question
Population
The trial concerns patients with small cell lung cancer, with separate descriptions for limited-stage small cell lung cancer (LS-SCLC) and extensive-stage small cell lung cancer (ES-SCLC). The registry also lists neuroendocrine neoplasm among the conditions. The record does not provide further eligibility details in the available information.
Intervention
The study examines pembrolizumab given alongside radiation-based treatment. Part A describes pembrolizumab with chemoradiotherapy for LS-SCLC, using cisplatin or carboplatin with etoposide and radiation therapy. Part B describes pembrolizumab with radiation therapy for ES-SCLC, beginning after chemotherapy is completed.
Comparator
There is no like-for-like control comparison identified in the registry record. Allocation is non-randomized, and the two parts concern different disease stages and treatment combinations. Their outcomes should not be treated as if they arose from randomized arms that differed only in pembrolizumab use.
Primary question
The primary outcome is dose-limiting toxicity, described as a count of DLTs. The registry frames this outcome as a safety assessment of MK-3475 (pembrolizumab) plus radiation for ES-SCLC. Although the trial also lists progression-free survival, overall survival, and overall response rate as secondary outcomes, results for these outcomes are not reported in the registry record.
3. Trial Design
This is a phase I, non-randomized, unmasked, parallel-model trial sponsored by M.D. Anderson Cancer Center. The registry lists enrollment as 83 and the status as completed. The recorded start date is 2015-07-22, and the primary completion date is 2025-12-23. These registry fields describe the study record; they do not provide outcome results or details of how enrollment was distributed across the treatment parts.
The trial has two treatment descriptions. Part A concerns LS-SCLC and combines pembrolizumab with chemoradiotherapy. The listed chemotherapy is cisplatin or carboplatin with etoposide, alongside radiation therapy. Part B concerns ES-SCLC and describes pembrolizumab with radiation therapy beginning after chemotherapy. The record describes repeated treatment courses, but does not provide a complete treatment schedule for every participant or clarify all treatment modifications.
Because allocation was non-randomized and the parts address different disease stages and regimens, they are not interchangeable treatment groups for a direct comparative-effect estimate. The registry explicitly cautions that the arms are not a like-for-like control comparison. No randomized control group is described in the record.
The registry lists four outcome measures and zero analyses. The primary outcome is DLT count; secondary outcomes include progression-free survival, overall survival, and overall response rate. The record does not report results for these measures, the analysis populations, or the statistical plan. Therefore, the design can be described, but comparative effectiveness or precision cannot be assessed from the listed outcome information.
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 | LS-SCLC (Limited-Stage Small Cell Lung Cancer) | ES-SCLC (Extended-Stage Small Cell Lung Cancer) |
|---|---|---|
| STARTED | 40 | 33 |
| COMPLETED | 37 | 33 |
| NOT COMPLETED | 3 | 0 |
Reasons for not completing this period:
| Reason | LS-SCLC (Limited-Stage Small Cell Lung Cancer) | ES-SCLC (Extended-Stage Small Cell Lung Cancer) |
|---|---|---|
| Withdrawal by Subject | 1 | 0 |
| Did not receive treatment per protocol | 1 | 0 |
| Patient canceled protocol treatment, wanted to get standard of care treatment | 1 | 0 |
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 | LS-SCLC (Limited-Stage Small Cell Lung Cancer) | ES-SCLC (Extended-Stage Small Cell Lung Cancer) | Total |
|---|---|---|---|---|
| Participants analysed | 37 | 33 | 70 | |
| Age, Categorical: <=18 years | Participants | 0 | 0 | 0 |
| Age, Categorical: Between 18 and 65 years | Participants | 19 | 17 | 36 |
| Age, Categorical: >=65 years | Participants | 18 | 16 | 34 |
| Age, Continuous | years | 63 (41 to 79) | 62 (37 to 80) | 62 (37 to 80) |
| Sex: Female, Male: Female | Participants | 21 | 13 | 34 |
| Sex: Female, Male: Male | Participants | 16 | 20 | 36 |
| Ethnicity (NIH/OMB): Hispanic or Latino | Participants | 0 | 0 | 0 |
| Ethnicity (NIH/OMB): Not Hispanic or Latino | Participants | 0 | 0 | 0 |
| Ethnicity (NIH/OMB): Unknown or Not Reported | Participants | 37 | 33 | 70 |
| Race (NIH/OMB): American Indian or Alaska Native | Participants | 0 | 0 | 0 |
| Race (NIH/OMB): Asian | Participants | 1 | 1 | 2 |
| Race (NIH/OMB): Native Hawaiian or Other Pacific Islander | Participants | 0 | 0 | 0 |
| Race (NIH/OMB): Black or African American | Participants | 3 | 0 | 3 |
| Race (NIH/OMB): White | Participants | 33 | 32 | 65 |
| Race (NIH/OMB): More than one race | Participants | 0 | 0 | 0 |
| Race (NIH/OMB): Unknown or Not Reported | Participants | 0 | 0 | 0 |
| Region of Enrollment: United States | participants | 37 | 33 | 70 |
6. Primary Endpoint
The registry lists the primary outcome as Dose Limiting Toxicity (DLT), measured over Median of 7.3 months (range: 1 to 13 months) following initation of treatment.
| Element | Registry entry |
|---|---|
| Result type | Number |
| Measure of spread | not applicable |
| Unit | Count of DLTs |
| Endpoint classification | not reduced to a single comparison |
The primary endpoint is dose-limiting toxicity (DLT), expressed as a count. DLT is used in early-phase research to characterize treatment-related safety and to inform decisions about tolerable dosing. In general, a count records how many events meet a defined criterion during a specified observation period. The clinical meaning of that count depends on the protocol’s DLT definition, assessment rules, and the population observed.
For this trial, the registry describes the primary outcome as safety of MK-3475 plus radiation for ES-SCLC. Its timeframe is stated as a median of 7.3 months, with a range of 1 to 13 months, following initiation of treatment. The record does not give the operational definition of a DLT, the actual DLT count, a denominator for that count, or an estimate of uncertainty. It also does not explain how the stated timeframe relates to individual DLT assessment.
Without the result and its denominator, the endpoint cannot establish the frequency of DLTs or support a comparison between treatment strategies. A DLT count is also not equivalent to a complete safety profile: other adverse events may differ in seriousness, timing, and clinical relevance. The registry’s separate serious adverse event figures should therefore be read as distinct safety information, not as a substitute for the missing primary endpoint result.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The registry record describes a phase I investigation of pembrolizumab used with radiation-based treatment in small cell lung cancer. Its primary outcome is a count of dose-limiting toxicities, framed as a safety outcome for ES-SCLC. However, no DLT result is reported. The record also lists progression-free survival, overall survival, and overall response rate, but gives no results or analyses for these secondary outcomes. Consequently, the posted information does not quantify the primary safety outcome or establish an effect on tumor response, progression, or survival.
The study is non-randomized and has two parts for different disease stages and treatment combinations. The LS-SCLC part includes chemotherapy with radiation and pembrolizumab; the ES-SCLC part describes pembrolizumab with radiation after chemotherapy. These differences matter: a contrast between the parts would combine differences in disease stage and treatment, and cannot isolate the effect of pembrolizumab. The registry itself cautions that the arms are not a like-for-like control comparison.
Safety information is reported by group. For LS-SCLC, the registry lists 37 at risk for serious adverse events and 5 affected; for ES-SCLC, it lists 33 at risk and 2 affected. It also reports other adverse-event figures and deaths by group. These counts describe the registry’s safety listings, but no comparative analysis, uncertainty interval, or adjustment for differences between groups is reported. A difference in raw counts would not by itself demonstrate that a treatment caused or prevented an event.
The serious adverse event terms reported most often include anemia, neutropenia, dyspnea, pneumonitis, infection, and rash, each with a registry-listed percentage. The record does not explain the denominator for those percentages or provide details about event timing, duration, severity grades, or attribution to treatment. Terms can also describe different events in the same participant; the registry information does not establish whether categories overlap.
Enrollment is recorded as 83, while safety information is presented with separate at-risk counts for the two groups. The record does not explain how those safety populations relate to total enrollment, nor does it provide analysis populations or missing-data handling. These gaps limit interpretation of both safety and efficacy. The appropriate reading is descriptive: the record identifies the study’s question and lists certain safety counts, but does not report the primary endpoint result or an inferential analysis supporting a treatment comparison.
9. Statistical Methods Explained
Several statistical ideas help interpret an early-phase, non-randomized study, but the registry record does not report a detailed analysis plan. The points below are general explanations, not claims about analyses performed in this trial.
What a DLT count can tell readers
A count endpoint records the number of events meeting a prespecified definition. Counts are often interpreted alongside the number of people observed and the duration of observation. A count on its own is difficult to compare across groups when group sizes or follow-up differ. A rate can account for exposure time, while a proportion can describe the share of people experiencing at least one event; each answers a different question. The registry reports the primary endpoint unit as a count of DLTs but does not state the observed count, its denominator, an exposure-adjusted rate, or a proportion with DLT.
For a count to be reproducible, the study protocol ordinarily specifies which events qualify, the observation window, and how uncertain cases are adjudicated. These details are not reported in the registry record. The stated timeframe is a median of 7.3 months, with a range of 1 to 13 months, following treatment initiation, but the record does not state how DLTs were assessed within that period. The timeframe alone cannot replace the missing outcome value.
Why an unadjusted comparison is limited
Randomization is a method for making treatment groups comparable, on average, with respect to both measured and unmeasured prognostic factors. This trial is non-randomized. Its two treatment parts also concern different disease stages and treatment combinations. Thus, the group-specific safety figures should not be interpreted as a randomized estimate of the effect of one regimen versus another. Differences could reflect patient characteristics, disease stage, treatment, observation time, or other factors that the record does not describe.
In general, adjustment for prognostic factors can sometimes improve comparisons in non-randomized studies, but adjustment does not automatically remove bias. The record does not report a covariate-adjusted analysis, the variables that might have been considered, or any model. It also lists zero analyses, so no statistical estimate or test is reported for the outcomes in this record.
Uncertainty and confidence intervals
A confidence interval is a statistical range that conveys the precision of an estimate under a specified method and assumptions. A broad interval generally reflects less precision than a narrow one. For event counts, suitable uncertainty methods depend on the estimand, event distribution, follow-up, and whether observations are independent. If counts vary more than a simple model expects, over-dispersion can make a basic model understate uncertainty; methods that allow extra variability may be more appropriate. These are general considerations. No confidence interval, model, dispersion estimate, or inferential result for DLT is reported in the registry record.
Likewise, a p-value, when used, addresses compatibility between data and a specified null hypothesis under a model. It does not measure the probability that a treatment works, establish causation, or convey the clinical importance of an effect. No p-value for the outcomes is reported in the registry record. Without an outcome estimate and its uncertainty, statistical significance cannot be assessed from the posted results.
How to understand the planning illustrations
Planning calculations based on an observed effect are not observed power. They illustrate what sample size might be needed under chosen assumptions, such as an effect size, allocation pattern, and significance level. The record’s stated planning assumptions describe a two-sided significance level of 0.05, equal allocation, and a normal approximation, with the target effect expressed as a fraction of the observed effect. It also distinguishes time-to-event planning, which uses a total event target, from other planning outputs, which use participants per arm.
Those assumptions are planning conventions, not proof that the trial itself was designed or analyzed that way. The sample-size assumption statement explicitly describes an illustration from the observed effect rather than the trial’s own design. The registry record does not report the original sample-size justification, target enrollment rationale, or a planning analysis for the primary endpoint. Any planning result should therefore be understood as conditional on its assumptions, not as evidence about the trial’s achieved power or outcome.
Outcome hierarchy and interpretation
The registry identifies DLT as primary and lists progression-free survival, overall survival, and overall response rate as secondary outcomes. Prespecifying an outcome hierarchy can help distinguish the main study question from additional questions. Yet the registry does not report outcome definitions, analysis methods, or results for the listed secondary endpoints. The number of listed outcomes alone does not reveal whether testing was planned, whether outcomes were adjusted for multiple comparisons, or how missing observations were handled. These issues cannot be resolved from the registry information available.
10. Multiplicity, Missing Data and Analysis Populations
The registry lists one primary outcome, dose-limiting toxicity, and secondary outcomes of progression-free survival, overall survival, and overall response rate. When several outcomes are examined, multiplicity can arise because repeated statistical tests increase the chance of at least one apparently notable result under a set of null hypotheses. General approaches include designating a primary endpoint, adjusting thresholds, or treating secondary analyses as exploratory. The registry record does not report a multiplicity strategy, so it is not possible to determine how any simultaneous outcome testing was intended to be interpreted.
The record lists four outcome measures and zero analyses. It does not report results for the primary or secondary endpoints, analysis populations, or the statistical plan. In particular, it does not say whether analyses were based on all enrolled participants, treated participants, or a defined safety or efficacy population. The relationship between enrollment of 83 and the safety at-risk counts is not explained.
Missing-data methods are also not reported in the registry record. This matters because missing outcomes, incomplete follow-up, or differing observation periods can affect estimates, especially for time-to-event outcomes such as progression-free and overall survival. Without definitions of censoring, follow-up completeness, or sensitivity analyses, the impact of missing information cannot be assessed. No assumption about the reason for missingness or the method used to address it is justified by the record.
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 |
|---|---|---|---|
| LS-SCLC (Limited-Stage Small Cell Lung Cancer) | 5 | 37 | 13.5% |
| ES-SCLC (Extended-Stage Small Cell Lung Cancer) | 2 | 33 | 6.1% |
Deaths
| Arm | Deaths (participants affected of at risk) |
|---|---|
| LS-SCLC (Limited-Stage Small Cell Lung Cancer) | 11 of 37 |
| ES-SCLC (Extended-Stage Small Cell Lung Cancer) | 20 of 33 |
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 |
|---|---|
| LS-SCLC (Limited-Stage Small Cell Lung Cancer) | 37 of 37 |
| ES-SCLC (Extended-Stage Small Cell Lung Cancer) | 30 of 33 |
Most frequent serious adverse event terms
| Event term | Organ system | LS-SCLC (Limited-Stage Small Cell Lung Cancer) | ES-SCLC (Extended-Stage Small Cell Lung Cancer) |
|---|---|---|---|
| Anemia | Blood and lymphatic system disorders | 4 of 37 | 0 of 33 |
| Neutropenia | Respiratory, thoracic and mediastinal disorders | 3 of 37 | 0 of 33 |
| Dyspnea | Respiratory, thoracic and mediastinal disorders | 2 of 37 | 0 of 33 |
| Infection | Infections and infestations | 2 of 37 | 0 of 33 |
| Pneumonitis | Respiratory, thoracic and mediastinal disorders | 2 of 37 | 0 of 33 |
| Rash | Skin and subcutaneous tissue disorders | 0 of 37 | 1 of 33 |
| Asthenia | General disorders | 0 of 37 | 1 of 33 |
| Parasthesia | Nervous system disorders | 0 of 37 | 1 of 33 |
| Autoimmune disorder | General disorders | 0 of 37 | 1 of 33 |
| Fat Atrophy | Gastrointestinal disorders | 1 of 37 | 0 of 33 |
Most frequent non-serious adverse event terms
| Event term | Organ system | LS-SCLC (Limited-Stage Small Cell Lung Cancer) | ES-SCLC (Extended-Stage Small Cell Lung Cancer) |
|---|---|---|---|
| Fatigue | General disorders | 22 of 37 | 13 of 33 |
| Dysphagia | Gastrointestinal disorders | 19 of 37 | 8 of 33 |
| Esophagitis | Gastrointestinal disorders | 17 of 37 | 8 of 33 |
| Dyspnea | Respiratory, thoracic and mediastinal disorders | 16 of 37 | 2 of 33 |
| Cough | Respiratory, thoracic and mediastinal disorders | 16 of 37 | 2 of 33 |
| Anemia | Blood and lymphatic system disorders | 12 of 37 | 2 of 33 |
| Nausea | Gastrointestinal disorders | 13 of 37 | 0 of 33 |
| Constipation | Gastrointestinal disorders | 7 of 37 | 2 of 33 |
| Radiation Dermatitis | General disorders | 4 of 37 | 3 of 33 |
| Diarrhea | Gastrointestinal disorders | 7 of 37 | 0 of 33 |
Serious events with the highest arm-level rate: anemia (10.8%), neutropenia (8.1%), dyspnea (5.4%), pneumonitis (5.4%), infection (5.4%).
The registry reports serious adverse event figures separately for LS-SCLC and ES-SCLC. For LS-SCLC, it lists 37 at risk and 5 affected; for ES-SCLC, it lists 33 at risk and 2 affected. The record also lists other adverse-event figures of 37 affected in LS-SCLC and 30 affected in ES-SCLC, as well as deaths of 11 and 20, respectively. These are descriptive registry counts, not treatment-effect estimates.
The registry lists anemia at 10.8%, neutropenia at 8.1%, dyspnea at 5.4%, pneumonitis at 5.4%, infection at 5.4%, and rash at 3.0% among the top serious adverse event terms. The denominator for these percentages is not reported in the registry record. Nor does the record provide detail on event grade, timing, duration, recurrence, or attribution to treatment.
Serious adverse events and DLTs are not necessarily identical categories. A DLT depends on a protocol-defined criterion, which is not described in the registry record. The serious-event counts therefore do not supply the missing DLT result. Counts from the two non-randomized parts should also not be treated as a controlled comparison, since the groups differ in disease stage and treatment description.
12. What the Result Does, and Does Not, Mean
The registry record establishes that this phase I study investigated pembrolizumab with radiation-based treatment in small cell lung cancer. It describes a chemoradiotherapy combination for LS-SCLC and a radiation-based combination after chemotherapy for ES-SCLC. It also identifies DLT count as the primary outcome and lists several secondary outcomes. These details clarify the study’s general purpose, but they do not provide the numerical primary outcome result.
The posted safety information gives group-specific counts for serious adverse events, other adverse events, and deaths, along with percentages for selected serious adverse event terms. Those figures describe what the registry records; they do not establish that pembrolizumab caused or prevented an event. Without a randomized, comparable control group and an analysis accounting for relevant differences, raw group counts cannot isolate treatment effects.
The record does not report DLT results, response results, progression-free survival results, overall survival results, confidence intervals, or statistical tests. It therefore does not show the magnitude or precision of an efficacy effect, and it cannot support a conclusion that the treatment improves or fails to improve an outcome. Absence of a reported result is not evidence that the outcome was zero or that no events occurred.
Likewise, the enrollment figure and at-risk counts do not by themselves explain who contributed to each analysis or how follow-up was handled. The relationship among enrollment, the two safety groups, and the outcome populations is not reported. Interpretations should remain limited to the trial design and the descriptive safety information actually recorded, without treating the study as a head-to-head comparison.
13. Why This Trial Matters Statistically
This trial is statistically instructive because its early-phase safety question is paired with a primary endpoint that is a count. Interpreting such an endpoint requires more than the count itself: readers need a clear event definition, the number observed, an appropriate denominator, and enough information about follow-up to understand exposure. The registry identifies the DLT count and a timeframe but does not report the result or the details needed to interpret its frequency.
The study also illustrates why design labels matter. Non-randomized parallel treatment parts do not automatically create a fair comparative experiment. Here, the parts address different disease stages and treatment combinations. A numerical contrast between them would mix those distinctions with any possible treatment effect. The record explicitly warns against treating the arms as a like-for-like control comparison.
Finally, the record distinguishes trial outcomes from planning illustrations. Sample-size calculations based on an observed effect depend on assumptions and are not observed power. The record describes such calculations as planning illustrations, while the original sample-size justification and statistical analysis plan are not reported. Together, these features show why outcome definitions, analysis populations, uncertainty estimates, and the connection between design and inference are essential to responsible interpretation.
14. Limitations
- The posted summary statistics are the only data these results rest on; patient-level data, full protocols and statistical analysis plans are not available.
- Recalculated results are simple, unadjusted calculations from posted summaries. They do not replace the sponsor's prespecified analysis.
The primary limitation for interpreting results is that the registry record does not report the primary DLT count. It also provides no results for progression-free survival, overall survival, or overall response rate. There is therefore no estimate of outcome magnitude or precision to evaluate.
The primary outcome description is framed around ES-SCLC, while the study includes a separate LS-SCLC part with a different treatment combination. The record does not provide enough detail to determine how the primary outcome relates to all enrolled participants or to the separate treatment parts. It also does not give a DLT definition, assessment rules, or an outcome denominator.
The design is non-randomized, and the registry cautions that the arms are not a like-for-like comparison. The treatment parts differ in disease stage and regimen, so group comparisons would be vulnerable to confounding. The record does not report adjusted analyses that might address measured differences.
Safety reporting is limited to group-level counts and selected event-term percentages. The denominator for the listed percentages, event timing, severity grades, attribution, and overlap among event categories are not reported in the registry record. The connection between enrollment of 83 and the at-risk counts is also not explained. Finally, the registry does not report the statistical plan, missing-data methods, analysis populations, or multiplicity strategy. These omissions constrain both safety interpretation and any assessment of efficacy.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Pembrolizumab and Concurrent Chemoradiotherapy or Radiation Therapy in Treating Patients With Small Cell Lung Cancer — NCT02402920.
- Registry record last updated 2026-03-10; status last verified 2026-02.
- Results first posted 2026-03-10.
- 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.
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18. Record Summary
The registry describes NCT02402920, a completed phase I, non-randomized, unmasked, parallel-model study sponsored by M.D. Anderson Cancer Center. Enrollment is listed as 83. The study evaluates pembrolizumab with chemoradiotherapy for LS-SCLC and with radiation therapy after chemotherapy for ES-SCLC.
The primary outcome is dose-limiting toxicity, recorded as a count and described as a safety assessment for ES-SCLC. The registry lists progression-free survival, overall survival, and overall response rate as secondary outcomes. It reports zero analyses and does not provide outcome results. Safety listings include serious adverse event counts, other adverse-event counts, deaths, and percentages for selected serious event terms. Because treatment allocation is non-randomized and the parts are not like-for-like control groups, those figures are descriptive rather than a causal comparison.