Combo of Cabozantinib With Abiraterone in Chemotherapy-Naïve Subjects With Bone-Metastatic CRPC: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Combo of Cabozantinib With Abiraterone in Chemotherapy-Naïve Subjects With Bone-Metastatic CRPC (NCT01995058), a randomized phase 2 study. The primary outcome is Radiographic Progression Free Survival (PFS).

2. Clinical Question

3. Trial Design

This was a randomized, open-label, parallel-group phase 2 study sponsored by Exelixis. It enrolled 54 participants with chemotherapy-naïve, bone-metastatic castration-resistant prostate cancer. The study began in 2014-02, and its primary completion date is listed as 2014-11. Its status is terminated. The registry record attributes early termination to business reasons and states that the study ended after 9 months.

Four groups were described. Three received cabozantinib with abiraterone and prednisone: cabozantinib 40 mg daily, cabozantinib 20 mg daily, or cabozantinib 20 mg every other day. The fourth received abiraterone and prednisone only. The parallel design means these groups were intended to be compared as separate treatment groups rather than as sequential treatment periods. The record specifies no masking, so the study was open-label.

Randomization and masking describe how a trial assigns treatment and whether participants or study personnel are kept unaware of assignment. The registry identifies the study as randomized and unmasked, but does not report how the random sequence was generated, how assignments were concealed, or the allocation ratio. It also does not report the planned number of participants by arm. Although the primary endpoint description refers to a protocol requirement of 140 PFS events, only 54 participants were enrolled and the trial ended early. The registry says the planned efficacy outcome was not collected or analyzed.

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

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: As pre-specified in the protocol, a total of 140 PFS events were required for this analysis; given that only 54 participants were enrolled and the study terminated early after 9 months, no data were collected or analyzed as planned for this outcome measure.

5. Baseline Characteristics

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

6. Primary Endpoint

The registry lists the primary outcome as Radiographic Progression Free Survival (PFS), measured over Up to 18 Months.

Radiographic progression-free survival (PFS) is a time-to-event endpoint. In this study, it was defined as the time from randomization to whichever occurred first: disease progression or death due to any cause. An Independent Radiology Committee was to assess progression, and the stated timeframe was up to 18 months.

In general, PFS can capture the time until disease worsens or death occurs, using an endpoint that includes radiographic assessment rather than relying only on a subjective report of symptoms. The registry record does not give further detail about the imaging schedule, the criteria used to define progression, or how disagreements in assessment would be handled. Those details are not reported in the registry record.

The record states that the study was terminated early for business reasons, after 9 months, and that no data were collected or analyzed as planned for this efficacy endpoint. It also states that 140 PFS events were required for the planned analysis. No PFS estimate, event count, comparison, or confidence interval is reported. The endpoint definition therefore explains what the study intended to measure, but the registry record does not provide an efficacy result for that measure.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

Several statistical ideas help distinguish what the study intended to estimate from what the registry record actually reports. The study was randomized and parallel-group: participants were assigned to one of four treatment groups, and the planned endpoint was to compare time to progression or death across treatment strategies. Randomization can support a fair comparison by balancing measured and unmeasured participant characteristics on average, but it does not ensure that a useful estimate will be available if the trial ends before the endpoint is analyzed. The record does not report the randomization method, allocation ratio, or a statistical analysis plan.

What a time-to-event endpoint represents

In general, time-to-event analysis uses both whether an event occurs and when it occurs. PFS in this study was defined from randomization to the earlier of disease progression or death due to any cause. A time-to-event analysis may account for participants whose event time is not observed during follow-up, often by treating their information as censored. Censoring means the event has not been observed by the last available time; it does not mean the participant experienced no event later. The registry record does not report whether any participants were censored, how follow-up ended for individual participants, or which time-to-event methods were planned.

For many time-to-event summaries, a hazard ratio or a survival curve may be used to describe how event experience changes over time. These are general methods, not results reported for this trial. The registry provides no PFS event data, survival curve, hazard ratio, or confidence interval. It is therefore not possible to evaluate the shape of the event-time pattern or the precision of an estimated treatment contrast from the record.

Why event counts matter

The registry states that 140 PFS events were required for the planned analysis and that only 54 participants were enrolled before early termination. In general, the amount of information in a time-to-event comparison depends strongly on the number of observed events, not only on the number initially enrolled. When few or no endpoint data are available for analysis, the estimated treatment effect may be unavailable or very imprecise. Here, the record explicitly says no data were collected or analyzed as planned for the primary efficacy outcome, so there is no reported estimate whose precision can be assessed.

This distinction is important: enrollment is a count of participants, while an event count is a count of endpoint occurrences. They are not interchangeable. The stated 140 PFS events were a protocol requirement for the planned analysis, not an observed result. The registry does not report that this event target was reached.

Planning assumptions and power

In general, power is the probability that a planned statistical test will detect an effect of a specified size under stated assumptions. A planning calculation is not observed power, and it does not describe the evidence actually obtained. The stated assumptions for planning illustrations are a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation; for time-to-event illustrations, the calculation is based on a total number of events using the Schoenfeld approach. These assumptions describe a planning framework, not the trial's observed allocation or the results of its four-group design.

Sample-size illustrations are hypothetical planning quantities. They cannot restore missing endpoint information or establish an effect. The registry record does not report an efficacy estimate for PFS, so there is no posted effect estimate from this trial to interpret as a clinical result. The registry also does not report the trial's own sample-size justification or the details of any analysis plan beyond the stated event requirement.

Multiplicity across treatment groups

Four groups create more than one possible comparison: each cabozantinib schedule could be considered against abiraterone and prednisone alone, and the cabozantinib schedules could also be compared with one another. When multiple hypotheses are tested, the chance of at least one false-positive finding can rise unless the analysis plan accounts for multiplicity. This is a general statistical concern, not evidence that a particular adjustment was or was not used in the study. The registry record does not report a multiplicity strategy, a hierarchy of comparisons, or efficacy tests.

Because no planned efficacy data were analyzed, there are no reported PFS hypothesis tests to interpret, adjusted or otherwise. The registry does report safety counts, but does not provide a statistical comparison of those counts. They should be read as descriptive information rather than as evidence from a formal test of differences between arms.

10. Multiplicity, Missing Data and Analysis Populations

The registry record does not report whether the planned analysis included an adjustment for multiple comparisons, a hierarchy among the three cabozantinib schedules, or a prespecified primary contrast against abiraterone and prednisone alone. With four treatment groups, multiple possible comparisons arise in general. A statistical plan ordinarily clarifies which comparisons are primary and how the interpretation accounts for repeated testing. That plan is not reported in the registry record.

For the primary efficacy outcome, the record states that no data were collected or analyzed as planned. Accordingly, it reports no PFS analysis population, participant disposition for the endpoint, handling of missing endpoint observations, censoring rules, or imputation method. The registry record does not say how participants who discontinued treatment or lacked later imaging would have been handled. No efficacy estimate is available to assess under different assumptions about missing observations.

The safety record gives group-level numbers at risk and numbers affected, but does not describe the analysis population rules, the safety observation period, or how incomplete safety follow-up was handled. It also does not report a statistical adjustment for comparisons of adverse events. These omissions limit interpretation of the recorded safety counts, especially for cross-arm comparisons.

These are reporting gaps in the registry record; they do not establish which methods were or were not used outside the information recorded. The planned efficacy analysis cannot be reconstructed from the stated endpoint definition and event target alone.

11. Safety Results

The registry reports serious adverse events as affected participants divided by participants at risk.

Deaths

Other (non-serious) adverse events

Participants with at least one non-serious event at or above the registry's 5.0% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: pulmonary embolism (8.3%), hypokalemia (8.3%), atrial fibrillation (7.7%), pneumonia (7.7%), septic shock (7.7%).

The registry reports serious adverse events and other adverse events by treatment group, along with deaths. For Arm 1, 14 participants were at risk for serious adverse events and 2 were affected; 14 were at risk for other adverse events and 13 were affected; deaths were 0. For Arm 2, the corresponding counts were 14 at risk and 4 affected for serious events, 14 at risk and 10 affected for other events, and 1 death. For Arm 3, the counts were 12 at risk and 1 affected for serious events, 12 at risk and 11 affected for other events, and 0 deaths. For Arm 4, the counts were 13 at risk and 1 affected for serious events, 13 at risk and 11 affected for other events, and 1 death.

The registry also lists pulmonary embolism and hypokalemia at 8.3%, atrial fibrillation, pneumonia, and septic shock at 7.7%, and anemia at 7.1% among the top serious adverse event terms. The record does not give arm-specific context for these listed percentages or further information about their denominators. Counts and percentages describe events recorded in the registry; without additional context, they do not establish causation or support a reliable comparison of treatment risks. The record does not report a statistical test of safety differences.

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

The registry record establishes that this was a randomized, open-label, parallel-group phase 2 study of cabozantinib schedules added to abiraterone and prednisone, with an abiraterone-and-prednisone-only group. It also establishes that 54 participants were enrolled and that the study was terminated early for business reasons. These are statements about the study's design and conduct, not evidence of comparative efficacy.

The intended primary outcome was PFS, defined using disease progression or death and assessed by an Independent Radiology Committee. The registry says no efficacy data were collected or analyzed as planned. As a result, the record does not provide an estimate of PFS for any group, a treatment contrast, or a measure of uncertainty. It cannot show whether the treatment groups differed in PFS, nor how precisely such a difference could be estimated.

The safety figures document counts of serious adverse events, other adverse events, and deaths by group, plus a list of serious event terms and percentages. These are descriptive registry entries. They do not, by themselves, establish that a treatment caused an event, and the record does not report formal statistical comparisons or enough detail to interpret the listed event percentages by treatment group.

In general, an inconclusive or unavailable estimate should not be treated as proof that groups are equivalent, nor as proof that a difference exists. In this case, the primary endpoint analysis is unavailable rather than a reported analysis with an uncertain estimate. The study's early termination and absence of planned efficacy analyses mean the posted information cannot answer its principal comparative efficacy question. The results should therefore be read as a record of an incomplete efficacy investigation, alongside limited descriptive safety counts, rather than as a treatment-effect finding.

13. Why This Trial Matters Statistically

This trial illustrates why a randomized design and a completed efficacy analysis are both necessary for a comparative clinical conclusion. Randomization describes how a study intends to create comparable groups. It does not itself produce an estimate of treatment effect. The registry record says the study was terminated early and that no data were collected or analyzed as planned for its primary efficacy endpoint. The planned PFS analysis required 140 events, while enrollment was 54 participants.

The distinction between enrollment and endpoint information is important in clinical research. A participant count records how many people entered a study; the number and timing of endpoint events determine what can be learned about a time-to-event outcome. When the planned analysis is not carried out, readers cannot assess the estimated effect, its uncertainty, or whether the evidence is compatible with a range of possible effects.

The four-group design also raises general questions about how a study prioritizes comparisons and handles multiple testing. Those questions cannot be resolved from this registry record because the statistical plan and multiplicity approach are not reported. The absence of an efficacy result makes it especially important not to infer conclusions from the design alone or from descriptive safety counts.

For biostatisticians and clinical researchers, the record is a useful example of separating protocol intent from reported evidence. It documents the endpoint definition, the event requirement, the treatment groups, early termination, and limited adverse-event information. It does not document the comparative PFS result the trial was designed to assess. Keeping those distinctions explicit prevents a missing analysis from being mistaken for a negative or equivalent result.

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 is that the registry record reports no efficacy data for the primary endpoint. The study was terminated early for business reasons after 9 months, and the planned PFS outcome was not collected or analyzed. The stated requirement was 140 PFS events, while 54 participants were enrolled. No PFS event count, estimate, confidence interval, or treatment comparison is reported.

The record identifies four treatment groups but does not report the randomization procedure, allocation ratio, participant numbers planned for each group, or detailed eligibility criteria. It also does not report imaging schedules, progression criteria beyond the endpoint definition, follow-up completeness, censoring rules, or the analysis populations. These details would be relevant to assessing the validity and precision of a time-to-event analysis.

The statistical analysis plan is not reported in the registry record. In particular, the record does not describe the intended primary contrast, handling of multiple comparisons, missing-data methods, or subgroup analyses. These absences prevent readers from determining how the planned efficacy analysis would have been carried out. They do not establish that any particular method was absent from other study documents.

Safety information is limited to group-level counts and a list of serious adverse event terms with percentages. The record does not provide arm-specific context for the listed percentages, detailed event timing, exposure duration, or formal comparisons. The available safety figures are therefore descriptive and should not be treated as a complete comparative safety analysis.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Combo of Cabozantinib With Abiraterone in Chemotherapy-Naïve Subjects With Bone-Metastatic CRPC — NCT01995058.
• Registry record last updated 2026-01-08; status last verified 2025-12.
• Results first posted 2026-01-08.
• Data retrieved from ClinicalTrials.gov on 2026-11-09.
• Group sizes, means, event counts and sponsor-reported p-values are reproduced as posted. Effect estimates, confidence intervals and p-values not attributed to the sponsor are independently calculated from the posted summary statistics.

18. Record Summary

NCT01995058 was a randomized, open-label, parallel-group phase 2 study sponsored by Exelixis. It enrolled 54 chemotherapy-naïve participants with bone-metastatic castration-resistant prostate cancer. Three groups received different cabozantinib schedules with abiraterone and prednisone; the fourth received abiraterone and prednisone only.

The primary endpoint was radiographic PFS, assessed by an Independent Radiology Committee, with a timeframe of up to 18 months. The registry record states that the study was terminated early for business reasons after 9 months. Although the planned analysis required 140 PFS events, no efficacy data were collected or analyzed as planned. The registry includes descriptive adverse-event counts and deaths by group, but no comparative efficacy result.