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 Survey of Cabozantinib Used To Treat People With Renal Cell Carcinoma (NCT04804813), a registered phase not stated study. The primary outcome is Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAE).
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT04804813 |
| Phase | Phase not stated |
| Condition | Renal Cell Carcinoma |
| Allocation | Not Stated |
| Design model | Not Stated |
| Masking | Not Stated |
| Enrollment | 388 |
| Arms in the primary outcome | n/a |
| Lead sponsor | Takeda |
| Results posted | Yes |
2. Clinical Question
Population
People with renal cell carcinoma treated in routine medical care in Japan. The registry lists enrollment of 388. The primary safety outcome uses a Safety Analysis Set defined as participants who completed the survey; the record does not explain how that definition relates to enrollment or to each reported group.
Intervention
Cabozantinib tablets. The arm description specifies a 60 mg tablet taken orally once daily for up to 26 weeks, with treatment as part of routine medical care. The sponsor was not involved in decisions about how participants were treated; it provided instructions to clinics for recording study information.
Comparator
The record lists cabozantinib monotherapy and cabozantinib plus nivolumab combination therapy. Allocation is not stated, and the record explicitly cautions that the arms are not a like-for-like control comparison. These groups therefore should not be treated as randomized treatment arms.
Primary question
How many participants had adverse events (AEs) and serious adverse events (SAEs) during follow-up of up to 26 weeks? The posted safety counts are separated by treatment group. The registry defines AEs as unfavorable medical occurrences temporally associated with medicinal-product use, whether or not judged related to the product. An SAE is defined by outcomes or clinical importance such as death, a life-threatening event, hospitalization, persistent or significant disability, a congenital anomaly, or another medically important event.
3. Trial Design
This record describes a drug-use surveillance survey, not a randomized controlled trial. It concerns cabozantinib use for renal cell carcinoma in Japan. The study is marked completed. The recorded start date is 2021-03-29, and the primary completion date is 2024-07-25. Enrollment is listed as 388.
The study description says that participants took cabozantinib according to their clinic’s standard practice and that doctors monitored side effects for 26 weeks. The sponsor was not involved in treatment decisions; it posted instructions for clinics on recording what happened. The arm description identifies a 60 mg oral tablet taken once daily for up to 26 weeks as part of routine medical care. The record also lists a group receiving cabozantinib with nivolumab.
The registry presents safety counts for cabozantinib monotherapy and cabozantinib plus nivolumab combination therapy. It does not state how participants were allocated to those groups. The record cautions that this is not a randomized comparison and that the arms are not like-for-like controls. Differences between their reported counts therefore cannot be interpreted as treatment effects: the groups may differ in ways that the posted information does not describe.
The primary outcome is a count of participants with AEs and SAEs, assessed up to 26 weeks. The stated population is the Safety Analysis Set, defined as participants who completed the survey. The record lists 13 outcome measures, including the secondary outcome “Percentage of Participants Who Achieve or Maintain Any Best Response.” Detailed results for that secondary outcome 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.
Before assignment: Participants with renal cell carcinoma who received Cabozantinib were enrolled. Participants received Cabozantinib as part of a routine medical care.
Overall Study
| Stage | Cabozantinib Monotherapy | Cabozantinib + Nivolumab Combination Therapy |
|---|---|---|
| STARTED | 325 | 63 |
| COMPLETED | 322 | 63 |
| NOT COMPLETED | 3 | 0 |
Reasons for not completing this period:
| Reason | Cabozantinib Monotherapy | Cabozantinib + Nivolumab Combination Therapy |
|---|---|---|
| Protocol Violation | 2 | 0 |
| Withdrawal by Subject | 1 | 0 |
Analysis population for the primary outcome, as defined in the registry: Safety Analysis Set, The safety analysis set was defined as all participants who completed the survey.
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.
Population: Safety Analysis Set, The safety analysis set was defined as all participants who completed the survey.
| Characteristic | Unit | Cabozantinib Monotherapy | Cabozantinib + Nivolumab Combination Therapy | Total |
|---|---|---|---|---|
| Participants analysed | 322 | 63 | 385 | |
| Age, Continuous | Years | 68.7 (SD 11.34) | 68.7 (SD 11.55) | 68.7 (SD 11.36) |
| Sex: Female, Male: Female | Participants | 98 | 17 | 115 |
| Sex: Female, Male: Male | Participants | 224 | 46 | 270 |
| Race and Ethnicity Not Collected | Participants | — | — | 0 |
6. Primary Endpoint
The registry lists the primary outcome as Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAE), measured over Up to 26 weeks.
| Element | Registry entry |
|---|---|
| Result type | Count Of Participants |
| Measure of spread | not applicable |
| Unit | Participants |
| Endpoint classification | Binary Endpoint |
The primary endpoint counts participants with adverse events (AEs) and serious adverse events (SAEs) during follow-up of up to 26 weeks. The unit is participants, and the registry defines the analysis population as the Safety Analysis Set: participants who completed the survey. The description treats an AE as an unfavorable medical occurrence temporally associated with use of a medicinal product, whether or not it has a clear causal relationship to the drug. An SAE is defined by specified consequences or clinical importance, including death, a life-threatening event, hospitalization or prolonged hospitalization, significant disability, a congenital anomaly, or another medically important event.
A safety count is useful for describing how many participants experienced events under the care and recording practices represented in the survey. It does not, by itself, establish that cabozantinib caused an event. The registry’s broad AE definition explicitly includes events without a clear causal relationship to treatment. Nor does a count describe the timing, duration, severity distribution, or recurrence of events unless those details are separately reported.
The endpoint is a count rather than a measure of time until an event or a change from baseline. The posted information gives group-specific counts for serious events and other events, but does not report an adjusted analysis or an overall primary-endpoint estimate. It also does not state how the listed category of other events relates to the formal AE definition.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The registry reports serious-event counts for cabozantinib monotherapy as 73 participants among 322 at risk, and for cabozantinib plus nivolumab combination therapy as 28 participants among 63 at risk. The corresponding counts listed for other events are 165 among 322 and 24 among 63. These are descriptive results for the groups recorded in the survey. The record does not define the “other” category further, so it should not automatically be read as a specific severity category.
The registry also lists deaths as 15 in the monotherapy group and 5 in the combination group. These are counts, not an attribution of cause. The record does not report whether those deaths were judged related to treatment, nor does it supply the details needed to interpret them as treatment-emergent events or as a comparative outcome.
Among the listed serious-event terms, interstitial lung disease and hepatic function abnormal are each reported as 6.3%; hypothyroidism is 4.8%; and vascular device infection, renal cell carcinoma, and adrenal insufficiency are each 3.2%. The denominator and calculation method for these percentages are not reported in the registry record. They should therefore be read as reported term percentages, not as estimates with a stated precision or as evidence of causal attribution.
The groups are not randomized control arms: allocation is not stated, and the registry explicitly warns that they are not a like-for-like comparison. Their counts should not be used to conclude that one regimen has greater or lesser risk than the other. Differences in group composition, treatment selection, observation, or recording could influence descriptive results, and the record does not provide information to adjust for such differences.
The registry does not report confidence intervals, hypothesis tests, or an adjusted model for these outcomes. Consequently, the precision of the group estimates and the uncertainty around comparisons are not quantified in the posted results. The numbers support a description of recorded events in the survey population, not a causal or comparative conclusion.
9. Statistical Methods Explained
What does a participant count represent? A participant count records how many people in a stated group experienced an outcome. For this survey, the primary endpoint is expressed in participants, and the registry defines the safety population as participants who completed the survey. The posted group information gives the number at risk and the number with serious events and other events. A count describes observed experience in the recorded group; it is not, on its own, an estimate of what would have happened under a different treatment.
Why does the denominator matter? A count is interpretable only alongside the population from which it came. The registry lists 322 at risk for the monotherapy group and 63 at risk for the combination-therapy group. It also reports enrollment of 388. The record does not explain the relationship between enrollment, the safety analysis definition, and these group denominators. It would be inappropriate to reconcile them by assumption or to treat all listed figures as if they described the same analysis population.
What does “adverse event” mean? The registry’s definition includes an unfavorable medical occurrence temporally associated with use of a medicinal product, even when there is no clear causal relationship. This is a safety-monitoring definition, not a claim that the medicine caused each event. The SAE definition is based on serious consequences or clinical importance. A reported count therefore needs to be kept distinct from an investigator’s assessment of relatedness, which is not given for the posted group counts.
Why are these not comparative treatment estimates? The record does not state how participants entered the monotherapy or combination group, and it expressly says the study is not a randomized comparison. General statistical principle: a randomized allocation can help make groups comparable at baseline, while nonrandomized groups may differ in health status, treatment decisions, or other factors that affect outcomes. Without information about allocation and adjustment, the group-specific counts are descriptive rather than a basis for attributing differences to treatment.
What would an interval estimate add? General statistical explanation: a confidence interval conveys uncertainty around an estimate under the assumptions of a statistical method. It can show that an estimate from observed data is not exact, and that plausible values may span a range. The registry record does not report confidence intervals for the safety counts or a comparative estimate. No precision range should be inferred from the counts alone.
Why might event counts vary more than a simple model expects? General statistical explanation: over-dispersion occurs when observed count variability exceeds what a statistical model assumes. It can arise when participants have different underlying risks or when events cluster. A model that ignores over-dispersion may understate uncertainty. This is a general consideration, not a reported finding about this survey. The registry does not report a model or an assessment of over-dispersion.
What is the role of a planned sample-size illustration? General statistical explanation: a planning calculation can illustrate how many participants per arm might be needed to detect a specified effect under stated assumptions. It is not a description of observed study precision or “observed power.” The stated illustration assumptions are a two-sided significance level of 0.05, equal allocation, a normal approximation, and an effect defined as a fraction of the observed effect. These are planning assumptions, not evidence that the survey used that design. The registry does not report the study’s sample-size justification or its own statistical planning method.
Were formal analyses specified? The registry lists no analyses. The statistical analysis plan, any interim analyses, and the methods used to produce the posted results are not reported in the registry record. Thus, readers cannot determine from the record whether the counts were adjusted, how missing observations were handled, or whether uncertainty estimates were calculated but not posted.
10. Multiplicity, Missing Data and Analysis Populations
The registry lists 13 outcome measures, including the primary safety outcome and a secondary outcome concerning participants who achieve or maintain any best response. It does not report a statistical analysis plan, a hierarchy for testing outcomes, or a method for controlling multiplicity. The number of analyses listed is zero. The registry record does not report whether outcomes were formally tested or whether any multiplicity adjustment was planned or applied. Without that information, the posted outcome list should be read as a record of measures, not as evidence that each measure was evaluated in a prespecified inferential framework.
The primary safety population is described as participants who completed the survey. The record does not report how many participants were excluded from that set, how incomplete records were handled, or whether missing outcome information was imputed. It also does not explain whether the group-specific “at risk” counts reflect the same completion rule. Missing-data assumptions and sensitivity analyses are not reported in the registry record.
These omissions matter because observed counts can depend on who was included and whether outcome recording was complete. General statistical principle: if missingness is related to health status, treatment, or an event, an analysis limited to complete records can differ from the experience of the full enrolled population. That possibility cannot be assessed from the posted description. The registry also does not report a prespecified statistical model, adjustment variables, or interim analyses. No assumptions about those methods should be made.
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 |
|---|---|---|---|
| Cabozantinib Monotherapy | 73 | 322 | 22.7% |
| Cabozantinib + Nivolumab Combination Therapy | 28 | 63 | 44.4% |
Deaths
| Arm | Deaths (participants affected of at risk) |
|---|---|
| Cabozantinib Monotherapy | 15 of 322 |
| Cabozantinib + Nivolumab Combination Therapy | 5 of 63 |
Other (non-serious) adverse events
Participants with at least one non-serious event at or above the registry's 5% reporting threshold.
| Arm | Participants affected of at risk |
|---|---|
| Cabozantinib Monotherapy | 165 of 322 |
| Cabozantinib + Nivolumab Combination Therapy | 24 of 63 |
Most frequent serious adverse event terms
| Event term | Organ system | Cabozantinib Monotherapy | Cabozantinib + Nivolumab Combination Therapy |
|---|---|---|---|
| Hypothyroidism | Endocrine disorders | 8 of 322 | 3 of 63 |
| Renal cell carcinoma | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | 8 of 322 | 2 of 63 |
| Interstitial lung disease | Respiratory, thoracic and mediastinal disorders | 3 of 322 | 4 of 63 |
| Hepatic function abnormal | Hepatobiliary disorders | 2 of 322 | 4 of 63 |
| Decreased appetite | Metabolism and nutrition disorders | 5 of 322 | 0 of 63 |
| Cardiac failure | Cardiac disorders | 3 of 322 | 1 of 63 |
| Pulmonary toxicity | Respiratory, thoracic and mediastinal disorders | 2 of 322 | 2 of 63 |
| Diarrhoea | Gastrointestinal disorders | 2 of 322 | 2 of 63 |
| Vascular device infection | Infections and infestations | 1 of 322 | 2 of 63 |
| Chronic kidney disease | Renal and urinary disorders | 3 of 322 | 0 of 63 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Cabozantinib Monotherapy | Cabozantinib + Nivolumab Combination Therapy |
|---|---|---|---|
| Palmar-plantar erythrodysaesthesia syndrome | Skin and subcutaneous tissue disorders | 40 of 322 | 8 of 63 |
| Diarrhoea | Gastrointestinal disorders | 35 of 322 | 4 of 63 |
| Hepatic function abnormal | Hepatobiliary disorders | 28 of 322 | 6 of 63 |
| Hypertension | Vascular disorders | 28 of 322 | 4 of 63 |
| Decreased appetite | Metabolism and nutrition disorders | 17 of 322 | 2 of 63 |
| Stomatitis | Gastrointestinal disorders | 17 of 322 | 0 of 63 |
Serious events with the highest arm-level rate: interstitial lung disease (6.3%), hepatic function abnormal (6.3%), hypothyroidism (4.8%), vascular device infection (3.2%), renal cell carcinoma (3.2%).
The serious-event figures are reported by treatment group: 73 participants among 322 at risk for cabozantinib monotherapy, and 28 among 63 at risk for cabozantinib plus nivolumab. The registry separately lists other-event counts of 165 among 322 and 24 among 63. It does not further define the “other” label, so the category should be described as recorded rather than assigned an unstated meaning.
Death counts are listed as 15 for monotherapy and 5 for combination therapy. The record does not state that these deaths were caused by treatment or give enough detail to determine their relationship to the primary endpoint. The listed serious-event terms and percentages are descriptive; the denominator for those percentages is not reported in the registry record.
These figures describe events recorded in a nonrandomized survey. They do not establish comparative safety between the groups, and an AE count does not establish causation. Allocation, methods for handling missing records, and adjusted estimates are not reported in the registry record.
12. What the Result Does, and Does Not, Mean
The posted results describe safety events recorded among participants in a Japanese cabozantinib drug-use survey. The registry reports serious-event and other-event counts separately for monotherapy and combination therapy, along with death counts and selected serious-event terms. Follow-up for the primary safety outcome is up to 26 weeks. These details provide a descriptive account of what was recorded in the groups and under the survey’s stated safety definitions.
The counts do not show that cabozantinib caused each event. The registry definition of an AE includes occurrences that are temporally associated with medicine use whether or not they are related to the medicine. The reported death counts also have no stated causal attribution. The listed event-term percentages do not have a reported denominator or method in the registry record, limiting their interpretation.
The results do not establish that one regimen is safer than the other. The study is not randomized, allocation is not stated, and the record cautions that the groups are not like-for-like controls. Group counts alone cannot account for differences in who received each treatment or in their care and recording. No adjusted comparisons or confidence intervals are reported.
The record also does not provide a complete account of missing data, the statistical analysis plan, or the precision of the estimates. The secondary best-response outcome is listed, but its detailed results are not reported in the registry record. Therefore, the available figures support a limited description of recorded safety events, not a causal conclusion, a treatment recommendation, or a broader estimate beyond the study population and follow-up described.
13. Why This Trial Matters Statistically
Drug-use surveillance addresses treatment as it is recorded in routine medical care, rather than under a randomized assignment described in the registry. That context is statistically important: the resulting counts can document observed safety experience, while treatment selection and group differences limit direct comparisons. This record makes that distinction explicit by stating that allocation is not reported and that the arms are not like-for-like controls.
The record also illustrates why outcome definitions and analysis populations matter. The primary measure counts participants with AEs and SAEs, while the safety population is defined by survey completion. The AE definition does not require a clear causal link to treatment. Keeping these details visible prevents a descriptive event count from being mistaken for a count of confirmed drug-caused events or a result for every enrolled participant.
For biostatistical interpretation, the gaps are consequential as well as the reported counts. The record does not report confidence intervals, adjusted comparisons, missing-data methods, or a statistical analysis plan. These omissions limit what can be concluded about precision and comparability. The survey is therefore informative as a registry description of recorded safety outcomes, but its posted information does not support a causal comparison between treatment groups.
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 key limitation is the nonrandomized design: allocation is not stated, and the registry cautions that the arms are not like-for-like controls. The monotherapy and combination groups therefore cannot be interpreted as if treatment had been randomly assigned. The record does not report participant characteristics or adjustment methods that might help characterize or account for group differences.
The primary safety population is defined as participants who completed the survey, but the record does not describe the completeness of outcome data or how missing information was handled. It lists enrollment of 388 and separate group denominators, without explaining their relationship. The source of the “at risk” counts and any exclusions are not reported in the registry record.
Further limits include the absence of reported confidence intervals, formal hypothesis tests, adjusted estimates, and analysis details. The listed serious-event term percentages have no stated denominator or calculation method. Death counts are not accompanied by causal attribution. The registry does not define the “other” event category further. Although best response is listed as a secondary outcome, its detailed results are not reported in the registry record. These gaps constrain interpretation of both the completeness and the precision of the posted safety description.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Survey of Cabozantinib Used To Treat People With Renal Cell Carcinoma — NCT04804813.
- Registry record last updated 2025-04-11; status last verified 2025-03.
- Results first posted 2025-04-11.
- 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
NCT04804813 is a completed drug-use surveillance survey of cabozantinib for renal cell carcinoma in Japan, sponsored by Takeda. The record lists enrollment of 388, a start date of 2021-03-29, and primary completion on 2024-07-25. Treatment was described as occurring in routine medical care, with safety monitoring for up to 26 weeks.
The primary outcome counts participants with AEs and SAEs in a Safety Analysis Set defined as survey completers. Safety counts are reported separately for cabozantinib monotherapy and cabozantinib plus nivolumab combination therapy. Allocation is not stated, and the registry warns that the groups are not like-for-like controls. The posted counts are descriptive and do not establish causation or comparative treatment effects. Statistical analysis details, confidence intervals, and missing-data methods are not reported in the registry record.