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 Lenvatinib in Advanced/Metastatic Neuroendocrine Prostate Cancer (NCT04848337), a na phase 2 study. The primary outcome is Radiologic Progression Free Survival (rPFS).
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT04848337 |
| Phase | Phase 2 |
| Condition | Prostate Cancer Metastatic, Neuroendocrine Tumors |
| Allocation | Not applicable (single group) |
| Design model | Single Group |
| Masking | None (open label) |
| Enrollment | 45 |
| Arms in the primary outcome | n/a |
| Lead sponsor | University of Michigan Rogel Cancer Center |
| Results posted | Yes |
2. Clinical Question
Population
The trial concerns patients with advanced or metastatic neuroendocrine prostate cancer. The registry lists prostate cancer metastatic and neuroendocrine tumors as conditions and records an enrollment of 45. Eligibility details beyond the brief description are not reported in the registry record.
Intervention
The study treatment combines lenvatinib and pembrolizumab. The recorded regimen is lenvatinib 20 mg orally on days 1–21 and pembrolizumab 200 mg intravenously over 30 minutes on day 1 of each 21-day cycle. Treatment may continue until radiographic progression, intolerable toxicity, or the patient or physician wishes to stop protocol therapy, with a maximum of 35 cycles.
Comparator
There is no separate comparator arm: the trial is recorded as single-group, with no allocation and no masking. The study therefore does not provide a randomized like-for-like comparison against another treatment or a control group.
Primary question
The primary endpoint is radiologic progression-free survival, defined from treatment initiation to radiologic progression of soft tissue lesions per RECIST 1.1 or death, whichever occurs first. The recorded endpoint timeframe is 6 months, with a 1-week window. A numerical rPFS result is not reported in the registry record, so the primary question cannot be answered from a posted numerical estimate.
The central statistical question is whether the recorded experience with the combination can be described in terms of the time until radiologic progression or death. In a single-group study, that description is about outcomes among participants receiving the study treatment; it is not an estimate of the treatment’s effect relative to an alternative. Without a reported rPFS estimate, its uncertainty, and details of the analysis population, readers cannot assess the magnitude or precision of the primary outcome from this record.
3. Trial Design
The registry identifies this as a Phase II, single-group trial with no allocation and no masking. The listed enrollment is 45. The sponsor is the University of Michigan Rogel Cancer Center. The trial status is active, not recruiting. The recorded start date is 2021-05-25, and the listed primary completion date is 2025-01-08; the latter is a registry date and does not by itself establish that the endpoint data have been analyzed or posted.
Participants in the study treatment arm receive lenvatinib 20 mg orally on days 1–21 and pembrolizumab 200 mg intravenously over 30 minutes on day 1. Each cycle is 21 days. The brief description says therapy continues until radiographic progression, intolerable toxicity, or patient or physician wishes to discontinue protocol therapy; up to 35 cycles may be administered. It also notes that on day 1, when both drugs are administered, patients should take lenvatinib according to their normal routine.
The listed primary outcome is radiologic progression-free survival, measured over 6 months with a 1-week window. Secondary outcomes are frequency and severity of adverse events, overall survival, objective response rate, and duration of response. The registry lists 5 outcome measures and 0 analyses. This record does not report detailed eligibility criteria, treatment adherence, follow-up procedures, or the statistical analysis plan. In particular, it does not report a rationale for the enrollment target, a planned interim analysis, or a detailed account of how outcome data were handled.
Because there is no randomized comparator, the design can describe outcomes observed in the treated group but cannot separate treatment-associated outcomes from other influences by means of a concurrent control comparison. Open-label conduct also means treatment assignment was not masked. Whether and how that could influence outcome assessment depends on procedures 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 | Study Treatment Arm |
|---|---|
| STARTED | 45 |
| COMPLETED | 30 |
| NOT COMPLETED | 15 |
Reasons for not completing this period:
| Reason | Study Treatment Arm |
|---|---|
| Adverse Event | 8 |
| Death | 2 |
| Withdrawal by Subject | 2 |
| Symptomatic Deterioration | 2 |
| Travel limitations due to natural disaster | 1 |
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 | Study Treatment Arm |
|---|---|---|
| Participants analysed | 45 | |
| Age, Customized | years | 69 (37 to 88) |
| Sex: Female, Male: Female | Participants | 0 |
| Sex: Female, Male: Male | Participants | 45 |
| Ethnicity (NIH/OMB): Hispanic or Latino | Participants | 4 |
| Ethnicity (NIH/OMB): Not Hispanic or Latino | Participants | 40 |
| Ethnicity (NIH/OMB): Unknown or Not Reported | Participants | 1 |
| Race (NIH/OMB): American Indian or Alaska Native | Participants | 0 |
| Race (NIH/OMB): Asian | Participants | 0 |
| Race (NIH/OMB): Native Hawaiian or Other Pacific Islander | Participants | 0 |
| Race (NIH/OMB): Black or African American | Participants | 4 |
| Race (NIH/OMB): White | Participants | 40 |
| Race (NIH/OMB): More than one race | Participants | 0 |
| Race (NIH/OMB): Unknown or Not Reported | Participants | 1 |
| Region of Enrollment: United States | participants | 45 |
6. Primary Endpoint
The registry lists the primary outcome as Radiologic Progression Free Survival (rPFS), measured over 6 months, with a 1-week window.
| Element | Registry entry |
|---|---|
| Result type | Median |
| Measure of spread | Full Range |
| Unit | months |
| Endpoint classification | Time-to-Event Analysis |
Radiologic progression-free survival (rPFS) is the primary endpoint. The registry defines it as the time from treatment initiation to radiologic progression of soft tissue lesions per RECIST 1.1 or death, whichever occurs first. Its stated timeframe is 6 months, with a 1-week window.
In general, a time-to-event endpoint measures how long it takes for a specified event to occur. Combining progression and death into a single endpoint means that either event can end the period counted as progression-free survival. This can be useful when the clinical question concerns the duration before progression or death, rather than response at a single assessment. It also requires clear event definitions and follow-up rules so that the event time is interpreted consistently.
The registry identifies the endpoint parameter as a median and its dispersion as a full range. In general, a median time is the point by which half of the observed event-time distribution has occurred, if the data permit that estimate. A full range describes the spread from the lowest to highest recorded value, but it does not convey the same information about precision as a confidence interval. Neither a numerical median nor a range is reported in the registry record. The record also does not report the number of rPFS events or the censoring approach, so readers cannot evaluate how much outcome information supports a median estimate.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The registry record identifies a defined primary endpoint and a single-group treatment regimen, but it does not report a numerical primary rPFS result. A result’s magnitude and precision therefore cannot be interpreted from the posted information. In particular, there is no reported median rPFS, full range, confidence interval, or sponsor-reported hazard ratio in the registry record. The absence of those values is not evidence for a particular outcome; it means the record does not support a numerical conclusion about the primary endpoint.
The trial enrolled 45 participants according to the registry. That number describes the recorded enrollment, not necessarily the number included in an endpoint analysis. The analysis population and the number with evaluable rPFS data are not reported in the registry record. Without those details, it is not possible to tell how many participants contributed follow-up to a specific estimate, how many had an event, or whether all enrolled participants were analyzed.
The study has no randomized comparator. Consequently, even if a single-group estimate were available, it would describe the observed experience in this treated group rather than quantify a causal difference from another treatment. The record does not provide a control outcome against which to compare rPFS. Differences between this group and patients treated elsewhere, or at another time, cannot be assessed as randomized treatment effects using the information recorded.
The endpoint uses radiologic progression or death, whichever comes first. In general, time-to-event results depend on both event ascertainment and follow-up. Participants who have not had a recorded event by the end of observation may be censored, and the handling of such observations affects interpretation. The registry does not report the censoring rules, assessment schedule, or number of censored observations. It also does not report whether the median could be estimated from the available follow-up.
Safety information is reported separately. The registry records serious adverse events affecting 39 of 45 participants at risk, other adverse events affecting 45 of 45 at risk, and 39 deaths. It also lists several serious adverse-event terms with percentages. Those figures should not be read as a comparison between treatment groups: only a study treatment arm is recorded. The adverse-event summaries do not establish that an event was caused by treatment, and the registry information does not give event timing or individual clinical context.
Overall, the record establishes the planned endpoint and describes some safety counts, but it does not post a numerical rPFS analysis. The difference between a specified outcome and a reported outcome matters: knowing what was intended to be measured does not reveal the observed estimate or its uncertainty.
9. Statistical Methods Explained
Time-to-event methods address outcomes measured as the time from a defined starting point until an event. In this trial, the registry defines the starting point as treatment initiation and the event as radiologic progression of soft tissue lesions per RECIST 1.1 or death, whichever occurs first. The endpoint is therefore a composite: progression and death are both counted as events. This definition helps clarify which outcome ends the measured time, but interpretation also depends on how events are assessed and how follow-up is recorded.
What does a median time describe?
The registry specifies a median parameter. In general, the median of an event-time distribution is the time at which the estimated proportion still without an event reaches half, when the data support that point. It is a measure of central tendency, not a statement that every participant experiences an event at that time. The median can be difficult or impossible to estimate if follow-up does not capture enough events. No numerical median rPFS is reported in the registry record, so the observed central event time cannot be described from the posted information.
The registry also specifies a full range as dispersion. In general, a range conveys the endpoints of the observed values and can be sensitive to extreme observations. It does not, on its own, express the statistical uncertainty around a median. A confidence interval would communicate a range of values compatible with the data under the analysis assumptions; its width would help readers judge precision. A confidence interval for rPFS is not reported in the registry record.
Why does censoring matter?
In time-to-event studies, some participants may not have a recorded event by the end of their available follow-up. Their event times are then not known exactly; methods can retain their observed follow-up information through censoring. In general, the validity of those methods relies on assumptions about why follow-up ended and whether that process is related to the event risk. The registry does not report censoring rules, the number censored, or the reasons for censoring. It also does not report the event count used for the primary analysis.
Follow-up and assessment procedures matter because progression is based on radiologic evaluation. In general, differences in when scans occur or in how progression is assessed can affect the recorded event time. The registry names RECIST 1.1 for soft tissue lesions, but scan timing, independent review, and adjudication procedures are not reported in the registry record. The record’s stated timeframe is 6 months, with a 1-week window; this does not specify the full follow-up schedule or establish that all participants were observed for the same duration.
What can a hazard ratio add?
In general, a hazard ratio compares event rates over time between groups under a model, and its interpretation depends on the comparison and model assumptions. This trial is single-group, so a hazard ratio would require a specified reference or another analysis context. No sponsor-reported hazard ratio is reported in the registry record. The record’s statistical-method note indicates that only sponsor-reported hazard ratios are used, so no hazard ratio should be inferred from other summaries.
How should the planning illustration be understood?
The sample-size assumptions describe a planning illustration based on an observed effect, not the trial’s own design. They state a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation; the effect to detect is a stated fraction of the observed effect. For time-to-event planning, the illustration expresses the requirement as a total number of events using the Schoenfeld approach. Other planning summaries express participants per arm.
These are general planning assumptions and are not evidence that the trial randomized participants to two arms. The actual design is recorded as single-group. The planning illustration is not an observed-power calculation and does not show that the trial achieved a particular power. A numerical observed effect on which to base such planning is not reported in the registry record. Any planning figures should therefore be treated as conditional illustrations, not as observed results or as the sponsor’s documented enrollment justification.
What does statistical significance not tell us?
In general, a significance test evaluates compatibility between data and a specified null model under stated assumptions. A p-value alone does not indicate the size of an effect, its clinical importance, or the probability that a hypothesis is true. Estimates and confidence intervals are needed to convey magnitude and precision. The registry lists 0 analyses and does not report a primary endpoint test or its p-value. No claim about statistical significance can be made from the record.
For this trial, the key interpretive constraint is not a choice among competing estimates but the absence of a posted numerical primary analysis. The design, endpoint definition, and some safety summaries are described; the primary time-to-event estimate and the analysis details needed to assess it are not reported in the registry record.
10. Multiplicity, Missing Data and Analysis Populations
The registry lists 5 outcome measures: radiologic progression-free survival, frequency and severity of adverse events, overall survival, objective response rate, and duration of response. The primary endpoint is identified, but the record does not report how the secondary outcomes were ordered for formal testing or whether any multiplicity adjustment was planned. That information is not reported in the registry record.
In general, testing multiple outcomes can increase the chance of observing at least one apparently unusual result when all null hypotheses are true. A prespecified hierarchy or adjustment can address that issue, while descriptive reporting may serve a different purpose. Without a reported testing plan and results, readers cannot determine whether confirmatory claims were protected against multiplicity or how secondary outcomes were intended to be interpreted.
Missing-data rules, analysis populations, and endpoint-specific denominators are not reported in the registry record. For rPFS, the record does not state how incomplete follow-up, missed assessments, or withdrawals were handled. It also does not state whether the analysis would include all enrolled participants or a defined subset. These omissions matter because the included participants and their follow-up can affect an estimated time-to-event outcome.
The registry lists 0 analyses. It does not report interim analyses, a statistical analysis plan, or methods for handling missing outcome data. Their absence from the record should not be taken to mean that a specific approach was or was not used; the approach is simply not reported.
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 |
|---|---|---|---|
| Study Treatment Arm | 39 | 45 | 86.7% |
Deaths
| Arm | Deaths (participants affected of at risk) |
|---|---|
| Study Treatment Arm | 39 of 45 |
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 |
|---|---|
| Study Treatment Arm | 45 of 45 |
Most frequent serious adverse event terms
| Event term | Organ system | Study Treatment Arm |
|---|---|---|
| Fatigue | General disorders | 13 of 45 |
| Hypertension | Cardiac disorders | 10 of 45 |
| Anorexia | Metabolism and nutrition disorders | 5 of 45 |
| Diarrhea | Gastrointestinal disorders | 3 of 45 |
| Adrenal insufficiency | Endocrine disorders | 2 of 45 |
| Aspartate aminotransferase increased | Investigations | 2 of 45 |
| Mucositis oral | Gastrointestinal disorders | 2 of 45 |
| Creatinine increased | Investigations | 1 of 45 |
| Dyspnea | Respiratory, thoracic and mediastinal disorders | 1 of 45 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Study Treatment Arm |
|---|---|---|
| Fatigue | General disorders | 41 of 45 |
| Nausea | Gastrointestinal disorders | 28 of 45 |
| Anorexia | Metabolism and nutrition disorders | 27 of 45 |
| Diarrhea | Gastrointestinal disorders | 26 of 45 |
| Hypothyroidism | Endocrine disorders | 16 of 45 |
| Dizziness | Nervous system disorders | 13 of 45 |
| Arthralgia | Musculoskeletal and connective tissue disorders | 12 of 45 |
| Dyspnea | Respiratory, thoracic and mediastinal disorders | 11 of 45 |
| Hypertension | Cardiac disorders | 11 of 45 |
| Rash maculo-papular | Skin and subcutaneous tissue disorders | 11 of 45 |
Serious events with the highest arm-level rate: fatigue (28.9%), hypertension (22.2%), anorexia (11.1%), diarrhea (6.7%), adrenal insufficiency (4.4%).
The registry records 45 participants at risk for serious adverse events and 39 affected. For other adverse events, it records 45 at risk and 45 affected. The death count is 39. These are counts in the registry record and should not be interpreted as comparisons between groups, because the trial has a single study treatment arm and no control arm.
The listed serious adverse-event terms and percentages are fatigue, 28.9%; hypertension, 22.2%; anorexia, 11.1%; diarrhea, 6.7%; adrenal insufficiency, 4.4%; and aspartate aminotransferase increased, 4.4%. The record does not give event timing or participant-level detail for these terms. The percentages should be read as the registry’s reported summaries, not as independently reconstructed rates or as evidence that a treatment caused an event.
In general, an adverse-event count describes recorded events or affected participants under the registry’s reporting conventions; it does not by itself establish causation, severity beyond the stated category, or comparative risk. The record does not provide the details needed to distinguish those interpretations further. The death count is reported separately and does not, by itself, identify cause or relationship to treatment.
12. What the Result Does, and Does Not, Mean
The record describes a Phase II investigation of pembrolizumab and lenvatinib in advanced or metastatic neuroendocrine prostate cancer. It specifies a single-group, unmasked design, a regimen, and radiologic progression-free survival as the primary endpoint. It also records secondary outcomes and selected safety summaries. These details establish what was registered and the broad structure of the investigation.
The record does not report a numerical rPFS result. Without an estimate and information about its precision, readers cannot determine the observed median time to progression or death or how uncertain that estimate is. Nor can they assess the number of endpoint events, the follow-up contributing to the estimate, or the handling of censored observations. A named endpoint is not itself an endpoint result.
The single-group design also limits what any outcome estimate could establish. It can describe outcomes among participants receiving the regimen, but it does not provide a randomized comparison that isolates a treatment effect relative to another option. The registry does not post a comparator outcome. Thus, neither the design nor the available record supports a claim about comparative benefit or harm.
The safety counts and listed serious adverse-event terms provide descriptive information, but they do not establish causation. A count of deaths does not specify cause or treatment relationship, and event percentages without fuller context cannot be treated as a comparative risk estimate. Further detail about event definitions and timing is not reported in the registry record.
In general, clinical interpretation combines the size of an estimate, its precision, the design, and the completeness of reporting. Here, the design and endpoint are identifiable, but a numerical primary analysis is absent. The record therefore supports a description of the trial’s registered question and some safety reporting, not a conclusion about the primary outcome or a comparison with other care.
13. Why This Trial Matters Statistically
This trial illustrates why statistical interpretation begins with the design rather than with an isolated outcome label. A single-group study can document the experience of participants treated with a specified regimen, but it lacks a concurrent randomized control group. That distinction determines which questions the design can answer. A time-to-event endpoint can be clearly defined while still not supporting a comparative treatment-effect estimate.
The choice of radiologic progression-free survival makes event definition and follow-up central. The registry specifies progression of soft tissue lesions per RECIST 1.1 or death, whichever occurs first. In general, that type of endpoint requires readers to consider event ascertainment, observation time, and censoring alongside the median. Without a posted event-time estimate and its precision, the endpoint definition cannot substitute for evidence about the observed outcome.
The registry also separates the primary endpoint from several secondary outcomes, including overall survival, objective response rate, duration of response, and adverse events. This range of outcomes can describe different aspects of a study, but their interpretation depends on an analysis plan and a transparent account of which analyses were performed. Such details are not reported in the registry record, which lists 0 analyses.
Finally, the record’s safety summaries show why descriptive counts must be distinguished from causal or comparative conclusions. The trial records 39 participants affected by serious adverse events among 45 at risk and 39 deaths, but there is no control arm for comparison. Statistical literacy means retaining the information these counts contain while avoiding conclusions they cannot support. The main lesson is to distinguish a registered question, a design capable of addressing that question, and a numerical analysis actually reported.
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 most important limitation for interpreting the primary endpoint is that a numerical rPFS result is not reported in the registry record. The record gives the endpoint definition, timeframe, median parameter, and full-range dispersion, but not the median, its range, a confidence interval, or an event count. It therefore does not permit assessment of the observed outcome or its precision.
The single-group design provides no randomized comparator. Any reported outcome from this group would be descriptive and could not, by itself, establish the effect of treatment relative to a control. The registry also records no allocation and no masking. Procedures for radiologic assessment, including scan timing or independent review, are not reported in the registry record.
Although enrollment is listed as 45, the number analyzed for rPFS and the endpoint-specific follow-up are not reported. The handling of censoring, missing assessments, withdrawals, and analysis populations is also not reported. These details would be needed to judge how the recorded enrollment relates to any outcome estimate.
The safety summaries are limited to counts and selected serious adverse-event terms with percentages. Event timing, individual-level context, attribution to treatment, and a comparator are not reported. The record lists 0 analyses, and does not report the statistical analysis plan, multiplicity approach, interim analyses, or sample-size justification. The recorded primary completion date does not establish that a primary analysis was completed or posted.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Pembrolizumab and Lenvatinib in Advanced/Metastatic Neuroendocrine Prostate Cancer — NCT04848337.
- Registry record last updated 2026-05-11; status last verified 2026-04.
- Results first posted 2026-02-12.
- 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
NCT04848337 is recorded as a Phase II, single-group trial sponsored by the University of Michigan Rogel Cancer Center. The study evaluates lenvatinib and pembrolizumab in advanced or metastatic neuroendocrine prostate cancer. Enrollment is listed as 45; the status is active, not recruiting. The recorded start date is 2021-05-25, and the listed primary completion date is 2025-01-08.
The primary endpoint is radiologic progression-free survival, defined from treatment initiation to radiologic progression of soft tissue lesions per RECIST 1.1 or death, whichever occurs first. The registry lists 5 outcome measures and 0 analyses. A numerical primary rPFS estimate, its precision, and the statistical analysis details are not reported in the registry record. The registry records serious adverse events affecting 39 of 45 participants at risk, other adverse events affecting 45 of 45 at risk, and 39 deaths.