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 Assess the Efficacy of Pembrolizumab Plus Radiotherapy or Ablation in Metastatic Colorectal Cancer Patients (NCT02437071), a non-randomized phase 2 study. The primary outcome is Number of Participants With Response.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT02437071 |
| Phase | Phase 2 |
| Condition | Metastatic Colorectal Cancer |
| Allocation | Non-Randomized |
| Design model | Parallel |
| Masking | None (open label) |
| Enrollment | 34 |
| Arms in the primary outcome | n/a |
| Lead sponsor | Memorial Sloan Kettering Cancer Center |
| Results posted | Yes |
2. Clinical Question
Population
People with metastatic colorectal cancer who were undergoing radiotherapy or ablation as standard therapy. The registry record does not report further eligibility details or the characteristics of participants enrolled in each treatment cohort.
Intervention
Pembrolizumab was combined with radiotherapy in one cohort and with ablation in another. The record describes the local treatment as addressing the tumors that were radiated or ablated. Its stated rationale was to examine whether the combination might prompt an immune response affecting cancer outside those locally treated tumors; that rationale is not evidence of an observed effect.
Comparator
There was no randomized control group. The registry lists nonrandomized treatment cohorts, not a like-for-like comparison of pembrolizumab plus local treatment against a control treatment. Participants received radiotherapy or ablation according to their standard therapy, so the two pathways should not be read as interchangeable groups.
Primary question
The primary outcome was the number of participants with a tumor response, assessed at approximately 9 weeks. The registry says that at least 3 responses per cohort would make further investigation of pembrolizumab plus radiotherapy and/or pembrolizumab plus ablation worth considering. The record does not report the response counts or an analysis answering that question.
3. Trial Design
NCT02437071 is listed as a phase 2 study of pembrolizumab plus radiotherapy or ablation in metastatic colorectal cancer. The registry status is completed, and the recorded enrollment is 34. The study began in 2015-04, with primary completion recorded as 2024-09-20. These registry entries describe the study record; they do not establish how many participants contributed to each outcome analysis.
The allocation is listed as nonrandomized, masking as none, and the model as parallel. The record describes two treatment pathways: pembrolizumab plus radiotherapy for participants undergoing radiotherapy as standard therapy, and pembrolizumab plus ablation for participants undergoing ablation as standard therapy. The official title calls the study single arm, while the arm descriptions identify these two pathways. The record does not explain this difference in terminology.
Because treatment assignment was not randomized, the cohorts are not a randomized comparison. The choice of local treatment may reflect clinical circumstances, and the registry does not report enough participant-level information to assess or adjust for possible differences between the groups. Any numerical contrast between their outcomes would therefore be descriptive, not a causal estimate of the relative effect of radiotherapy versus ablation.
The record lists pembrolizumab as a drug, radiotherapy as radiation, and radiofrequency ablation as a procedure. It also lists toxicities as a secondary outcome. Details such as eligibility criteria, treatment schedules, follow-up beyond the primary timeframe, and the analysis populations are not reported in the registry record.
4. Participant Flow and Accounting
The registry reports how participants moved through each stage of the study. All counts below are exactly as posted; missing counts are not inferred from other stages.
Overall Study
| Stage | Pembrolizumab Plus Radiotherapy | Pembrolizumab Plus Ablation |
|---|---|---|
| STARTED | 25 | 9 |
| COMPLETED | 24 | 9 |
| NOT COMPLETED | 1 | 0 |
Reasons for not completing this period:
| Reason | Pembrolizumab Plus Radiotherapy | Pembrolizumab Plus Ablation |
|---|---|---|
| Withdrawal by Subject | 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 | Pembrolizumab Plus Radiotherapy | Pembrolizumab Plus Ablation | Total |
|---|---|---|---|---|
| Participants analysed | 25 | 9 | 34 | |
| Age, Continuous | years | 60 (18 to 80) | 59 (35 to 72) | 59.7 (18 to 80) |
| Sex: Female, Male: Female | Participants | 12 | 2 | 14 |
| Sex: Female, Male: Male | Participants | 13 | 7 | 20 |
| Ethnicity (NIH/OMB): Hispanic or Latino | Participants | 0 | 1 | 1 |
| Ethnicity (NIH/OMB): Not Hispanic or Latino | Participants | 12 | 4 | 16 |
| Ethnicity (NIH/OMB): Unknown or Not Reported | Participants | 13 | 4 | 17 |
| Race (NIH/OMB): American Indian or Alaska Native | Participants | 0 | 0 | 0 |
| Race (NIH/OMB): Asian | Participants | 3 | 1 | 4 |
| Race (NIH/OMB): Native Hawaiian or Other Pacific Islander | Participants | 0 | 0 | 0 |
| Race (NIH/OMB): Black or African American | Participants | 0 | 1 | 1 |
| Race (NIH/OMB): White | Participants | 22 | 7 | 29 |
| 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 | 25 | 9 | 34 |
6. Primary Endpoint
The registry lists the primary outcome as Number of Participants With Response, measured over approximately 9 weeks.
| Element | Registry entry |
|---|---|
| Result type | Count Of Participants |
| Measure of spread | not applicable |
| Unit | Participants |
| Endpoint classification | Binary Endpoint |
The primary outcome is the number of participants with a tumor response, with assessment at approximately 9 weeks. This is a binary participant-level outcome: each participant is classified according to whether a response was observed, and the outcome is expressed as a count. The registry does not report the response count, the denominator used for the primary analysis, or an effect estimate.
The description refers to response criteria for target lesions assessed by MRI. It defines complete response as disappearance of all target lesions and partial response as at least a 30% decrease in the sum of their longest diameters. Stable disease is described as neither partial response nor progressive disease. Progressive disease includes at least a 20% increase in the sum of longest diameters relative to the smallest sum recorded in the study, progression of non-target lesions, or new lesions.
In general, a response endpoint gives a prespecified way to classify tumor change at a follow-up assessment. The registry’s stated decision rule is that at least 3 responses per cohort would support considering further investigation. That rule is a threshold for whether to consider additional study, not a reported result. The endpoint description refers both to RECIST 1.1 for the response threshold and RECIST v1.0 for the lesion definitions. The record does not explain this difference.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The registry record does not report primary outcome results or analysis entries. It therefore does not establish how many participants had a response in either cohort, whether the stated response threshold was met, or how precise any response estimate would be. No primary outcome confidence interval, p-value, or adjusted analysis is reported in the registry record. Enrollment alone cannot answer the response question: the number enrolled is not necessarily the denominator in an outcome analysis.
The design also limits what can be learned by comparing the two treatment pathways. Allocation was nonrandomized, and participants received radiotherapy or ablation as standard therapy. People in the two cohorts could differ in ways related to treatment choice and prognosis. Without random assignment or sufficient adjustment information, an observed difference between cohort counts could reflect those differences, chance, or treatment effects. The registry record does not report an adjusted comparison that could address these concerns.
The response threshold has a particular interpretation. The record states that at least 3 responses in a cohort would make further investigation worth considering. This is a study-development criterion, not a claim that a treatment is effective, nor a formal demonstration that the response rate differs from a comparator. The registry does not report the statistical basis for the threshold or a sample-size justification.
Safety information is reported as counts by cohort. For serious adverse events, the record lists 21 participants affected among 25 at risk in the radiotherapy cohort and 9 among 9 at risk in the ablation cohort. It also lists other adverse events affecting 25 among 25 at risk and 9 among 9 at risk, respectively. These counts should be interpreted according to the registry’s recorded categories; the record does not give enough detail to determine event timing, severity grading, relatedness to study treatment, or whether events overlapped within participants.
The registry also lists deaths and serious adverse-event terms. Counts in a safety record do not by themselves establish that an event was caused by pembrolizumab or by local treatment. The cause, timing, and treatment attribution of the recorded deaths are not reported in the registry record. The posted information supports description of recorded counts, but not a conclusion about comparative safety or benefit.
9. Statistical Methods Explained
What does a participant count measure?
The primary endpoint is a count of participants classified as having a response. In general, a count is a direct summary of how many people meet a defined outcome rule. To interpret it as a response rate, the count must be considered alongside the number of participants assessed and the handling of missing assessments. The registry record does not report the primary response count, the analysis denominator, or how missing response assessments were handled.
The response definition matters because it determines which observations qualify. Here, the registry describes complete response, partial response, stable disease, and progressive disease using lesion changes and MRI assessment. In general, these categories make the endpoint more reproducible than an informal judgment, but reproducibility depends on applying the stated criteria consistently. The record uses RECIST 1.1 in its decision threshold and RECIST v1.0 in its lesion definitions. How those references were reconciled in practice is not reported in the registry record.
Why does randomization matter?
In general, randomization aims to balance measured and unmeasured prognostic factors across treatment groups. It makes a between-group contrast more credible as an estimate of treatment effect, subject to follow-up, outcome measurement, and analysis assumptions. This study is listed as nonrandomized. Its two cohorts followed different local-treatment pathways, and the record says that participants were undergoing radiotherapy or ablation as standard therapy. A comparison between those cohorts cannot be interpreted as if treatment had been randomly assigned.
Parallel treatment pathways can still provide descriptive information about the outcomes recorded in each cohort. However, differences in disease features, participant health, treatment selection, or other factors could influence the observed results. The registry record does not give baseline characteristics or an adjusted cohort comparison that would show whether such factors were considered. Consequently, no causal interpretation of a difference between the pathways is supported by the information recorded.
What would an interval or p-value add?
In general, a confidence interval describes the range of estimates compatible with the data under a specified statistical model and procedure. A narrower interval indicates greater precision under those assumptions; a wider one indicates greater uncertainty. A p-value summarizes how surprising the data would be under a specified null hypothesis and model. Neither statistic, on its own, establishes clinical importance or removes design limitations.
No primary outcome confidence interval or p-value is reported in the registry record. There are no analysis entries listed for the outcomes. The response count, denominator, and analysis method are also not reported, so the primary endpoint cannot be independently summarized from the registry entry. Absence of an analysis entry does not establish what analyses may have been conducted outside the registry record.
How should the response threshold be understood?
The registry states that at least 3 responses per cohort would make further investigation worth considering. This is a decision rule for pursuing additional study, not an estimate of treatment effect and not a significance test. In general, a threshold chosen for further investigation can help guide development decisions, but its interpretation depends on the clinical and statistical rationale behind it. That rationale and a formal sample-size justification are not reported in the registry record.
The record describes planning illustrations based on an observed effect, with a two-sided significance level of 0.05, equal allocation, and a normal approximation. Such calculations are planning aids, not observed power. They depend on assumptions about the effect to be detected and the analysis. The actual illustration values and the observed primary effect are not reported in the registry record, so no numerical sample-size implication can be stated. A planning calculation cannot substitute for the trial’s observed response data.
What does over-dispersion mean in general?
For outcomes modeled as counts, over-dispersion means that variability is greater than expected under a simple model such as a Poisson model. In general, ignoring over-dispersion can make uncertainty appear smaller than it is. The primary endpoint in this study is described as a participant count with a binary response classification, rather than a repeated event count for each participant. The registry record does not report a model or dispersion estimate for the primary analysis, so there is no basis to say that an over-dispersion adjustment was used or was required.
What can the safety counts support?
Safety summaries count participants with recorded events within a stated risk group. In general, these counts describe how many people were recorded as affected; they do not convey event timing, duration, severity, treatment attribution, or repeat events unless those details are separately defined. Counts can be difficult to compare across cohorts when treatment assignment is not randomized or when the risk groups differ. Here, the registry lists at-risk and affected counts for serious and other adverse events, but does not provide detailed event-level analysis or a comparative model.
10. Multiplicity, Missing Data and Analysis Populations
The registry lists two outcome measures and identifies response as primary and toxicities as secondary. It does not report an outcome-testing hierarchy, a family-wise error procedure, or another multiplicity strategy. A multiplicity plan matters when several outcomes or analyses are tested, because repeated testing can increase the chance of a nominally notable result arising by chance. Without a stated plan and outcome analyses, there is no basis to determine how multiplicity was addressed.
The record contains no analysis entries. Primary response counts, denominators, estimates, confidence intervals, and p-values are not reported in the registry record. The listed enrollment cannot be treated as the number analyzed for each endpoint. The record does not say how participants with missing assessments, withdrawals, or incomplete follow-up were handled, or whether the analysis used an intention-to-treat, per-protocol, or other population.
For the safety outcome, the record gives at-risk and affected counts by cohort, but does not describe the definitions used for inclusion in each risk group, follow-up duration for safety, missing safety information, or event attribution. These omissions matter because a count’s meaning depends on who was observed and over what period. The registry does not report an approach to multiplicity across safety terms or an analysis plan for comparing safety between cohorts.
These details are not reported in the registry record; their absence should not be taken as proof that they were not considered or analyzed elsewhere. The record alone does not support reconstruction of the missing-data strategy, analysis populations, or statistical plan.
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 |
|---|---|---|---|
| Pembrolizumab Plus Radiotherapy | 21 | 25 | 84.0% |
| Pembrolizumab Plus Ablation | 9 | 9 | 100.0% |
Deaths
| Arm | Deaths (participants affected of at risk) |
|---|---|
| Pembrolizumab Plus Radiotherapy | 21 of 25 |
| Pembrolizumab Plus Ablation | 9 of 9 |
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 |
|---|---|
| Pembrolizumab Plus Radiotherapy | 25 of 25 |
| Pembrolizumab Plus Ablation | 9 of 9 |
Most frequent serious adverse event terms
| Event term | Organ system | Pembrolizumab Plus Radiotherapy | Pembrolizumab Plus Ablation |
|---|---|---|---|
| Death NOS | General disorders | 21 of 25 | 9 of 9 |
| Back Pain | Musculoskeletal and connective tissue disorders | 4 of 25 | 0 of 9 |
| Abdominal Pain | Gastrointestinal disorders | 2 of 25 | 1 of 9 |
| Dehydration | Metabolism and nutrition disorders | 1 of 25 | 0 of 9 |
| Pleural Effusion | Respiratory, thoracic and mediastinal disorders | 1 of 25 | 0 of 9 |
| Dyspnea | Respiratory, thoracic and mediastinal disorders | 1 of 25 | 0 of 9 |
| Gastric Obstruction | Gastrointestinal disorders | 1 of 25 | 0 of 9 |
| Small Intestinal Obstruction | Gastrointestinal disorders | 1 of 25 | 0 of 9 |
| Blood Bilirubin Increased | Investigations | 0 of 25 | 1 of 9 |
| Hepatic Failure | Hepatobiliary disorders | 1 of 25 | 0 of 9 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Pembrolizumab Plus Radiotherapy | Pembrolizumab Plus Ablation |
|---|---|---|---|
| Anemia | Blood and lymphatic system disorders | 25 of 25 | 0 of 9 |
| Fatigue | General disorders | 17 of 25 | 8 of 9 |
| Abdominal pain | Gastrointestinal disorders | 13 of 25 | 3 of 9 |
| Back pain | Musculoskeletal and connective tissue disorders | 10 of 25 | 4 of 9 |
| Constipation | Gastrointestinal disorders | 11 of 25 | 3 of 9 |
| Nausea | Gastrointestinal disorders | 12 of 25 | 1 of 9 |
| Diarrhea | Gastrointestinal disorders | 12 of 25 | 0 of 9 |
| Dyspnea | Respiratory, thoracic and mediastinal disorders | 8 of 25 | 3 of 9 |
| Peripheral sensory neuropathy | Nervous system disorders | 10 of 25 | 1 of 9 |
| Vomiting | Gastrointestinal disorders | 9 of 25 | 2 of 9 |
Serious events with the highest arm-level rate: death nos (100.0%), back pain (16.0%), abdominal pain (11.1%), blood bilirubin increased (11.1%), thromboembolic event (11.1%).
For serious adverse events, the registry lists 25 participants at risk and 21 affected in the pembrolizumab plus radiotherapy cohort, and 9 at risk and 9 affected in the pembrolizumab plus ablation cohort. For other adverse events, it lists 25 at risk and 25 affected in the radiotherapy cohort, and 9 at risk and 9 affected in the ablation cohort. These are recorded counts; they do not by themselves describe when events occurred or how long participants were followed.
The record separately lists deaths as 21 in the radiotherapy cohort and 9 in the ablation cohort, and includes Death NOS at 100.0% among its listed serious terms. The denominator and precise interpretation of that percentage are not reported in the registry record. The listed death counts should not be assumed to indicate treatment causation. Attribution, timing, causes, event-level overlap, and severity grading are not reported in the registry record.
Because treatment assignment was nonrandomized and the cohorts are not like-for-like controls, these safety counts do not establish a comparative safety effect. They are registry-reported descriptive figures, not evidence that pembrolizumab or either local treatment caused a particular event.
12. What the Result Does, and Does Not, Mean
This study record describes a phase 2 investigation of pembrolizumab combined with radiotherapy or ablation in metastatic colorectal cancer. Its primary question concerned the number of participants with a tumor response at approximately 9 weeks, and it set a threshold of at least 3 responses per cohort for considering further investigation. The registry record does not report the response counts or an analysis of that endpoint. It therefore cannot show whether the threshold was reached.
The study’s nonrandomized design is central to interpretation. Radiotherapy and ablation were separate treatment pathways for participants receiving local treatment as standard therapy. The cohorts were not assigned at random and are not a like-for-like control comparison. Even if response or safety counts were available for each, a difference would not by itself establish that the local treatment choice caused the difference.
The safety record gives counts of participants affected by serious and other adverse events and separately records deaths. Those counts are useful as a description of what the registry lists, but they do not identify cause, timing, treatment relatedness, or the effect of differing follow-up. They should not be treated as evidence of treatment benefit or harm without the missing context and analysis.
In general, a study can help frame a question for further research without resolving that question. Here, the stated response threshold is a criterion for considering additional investigation. It is not a clinical conclusion. The registry does not report an effect estimate, uncertainty interval, comparative analysis, or detailed statistical plan. The available entry therefore characterizes the study’s design, endpoint, and recorded safety counts, but does not establish whether the combination approach changed tumor outcomes or how its outcomes compare with another treatment.
13. Why This Trial Matters Statistically
Statistically, this study illustrates the distinction between a prespecified development threshold and a treatment-effect estimate. The registry’s rule that at least 3 responses per cohort would make further investigation worth considering is a decision criterion. It does not replace a response estimate with its uncertainty, a comparison group, or a defined inferential analysis. Since response results are not reported in the registry record, the threshold cannot be evaluated from the posted information.
The study also shows why treatment allocation is important when interpreting separate cohorts. Nonrandomized treatment pathways can be clinically meaningful, but people receiving radiotherapy and ablation may differ for reasons related to treatment selection. A comparison between their outcomes would not isolate the effect of one approach unless the design and analysis adequately addressed those differences. The registry record does not report such an adjusted comparison.
Finally, the record highlights that safety counts need context. At-risk groups and affected counts give a basic description, while follow-up time, attribution, event definitions, missingness, and analysis populations determine how far interpretation can go. The reported counts do not themselves answer whether events were caused by treatment or whether risks differed between pathways.
These considerations are broadly relevant to phase 2 research: a clear endpoint and decision rule can guide later investigation, while design, analysis, and reporting determine whether results support a reliable conclusion. In this record, the absence of primary outcome analyses leaves the central response question 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.
The primary limitation for interpretation is that the registry record does not report the response count, denominator, or analysis for the primary endpoint. The stated response threshold therefore cannot be assessed. The record also does not report confidence intervals, p-values, or a treatment-effect estimate.
Nonrandomized allocation limits comparisons between the radiotherapy and ablation cohorts. Participants entered different treatment pathways based on standard therapy, and the record does not provide baseline characteristics or an adjusted comparison. The registry also does not explain why the official title uses single-arm terminology while the arm descriptions list two treatment pathways.
The endpoint description refers to RECIST 1.1 in the response threshold and RECIST v1.0 in its lesion definitions. How these references were applied together is not reported. Details on assessment procedures, independent review, missing assessments, analysis populations, and follow-up completeness are also not reported in the registry record.
Safety information is limited to recorded counts and listed terms. The record does not report detailed event timing, treatment relatedness, causes of death, event overlap, or a comparative safety analysis. The interpretation of the listed Death NOS percentage is unclear because its denominator is not reported. The record also does not report a multiplicity approach, formal sample-size justification, or a full statistical analysis plan. These limitations restrict conclusions to the study design and posted descriptive safety information.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Assess the Efficacy of Pembrolizumab Plus Radiotherapy or Ablation in Metastatic Colorectal Cancer Patients — NCT02437071.
- Registry record last updated 2025-12-05; status last verified 2024-09.
- Results first posted 2025-12-05.
- 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
NCT02437071 is a completed phase 2 study of pembrolizumab plus radiotherapy or ablation in metastatic colorectal cancer. The registry lists nonrandomized allocation, no masking, a parallel model, and enrollment of 34. The primary endpoint was the number of participants with a response at approximately 9 weeks, with a stated threshold of at least 3 responses per cohort for considering further investigation.
The record lists serious and other adverse-event counts by treatment pathway and separately lists deaths. It does not report primary response results, outcome analyses, confidence intervals, p-values, or analysis populations. The nonrandomized pathways do not form a like-for-like control comparison, and the registry record does not report sufficient detail to support causal or comparative conclusions.