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 Early Switch From First-Line Docetaxel/Prednisone to Cabazitaxel/Prednisone and the Opposite Sequence, Exploring Molecular Markers in Men With Metastatic Castration-Resistant Prostate Cancer (mCRPC) (NCT01718353), a randomized phase 2 study. The primary outcome is Percentage of Participants With PSA Response.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT01718353 |
| Phase | Phase 2 |
| Condition | Prostate Cancer Metastatic |
| Allocation | Randomized |
| Design model | Parallel |
| Masking | None (open label) |
| Enrollment | 63 |
| Arms in the primary outcome | n/a |
| Lead sponsor | Sanofi |
| Results posted | Yes |
2. Clinical Question
Population
Men with metastatic castration-resistant prostate cancer who had not received prior chemotherapy were the intended study population. The registry reports an enrollment of 63 and says the primary PSA response analysis was performed on all randomized participants. It does not report the number randomized in each initial-treatment group in the primary outcome description.
Intervention
One strategy began with docetaxel plus prednisone. If PSA had not decreased by at least 30% from baseline at the end of cycle 4, participants switched to cabazitaxel. The other strategy began with cabazitaxel plus prednisone and switched to docetaxel when the same PSA response threshold was not met. The registry describes prednisone or prednisolone as the accompanying corticosteroid.
Comparator
The comparison was between the two randomized starting sequences: docetaxel followed, when indicated, by cabazitaxel; or cabazitaxel followed, when indicated, by docetaxel. The registry says efficacy data were combined across initial taxanes, rather than reported separately by the taxane started. Therefore, the available primary outcome description does not provide a direct result for one starting sequence versus the other.
Primary question
The principal PSA question was whether participants had a sustained decrease of at least 50% from baseline at any time during the trial. The study also identified circulating tumor cell biomarkers, percent androgen receptor nuclear localization and microtubule bundling, as primary outcomes. The registry record does not report observed values for these primary measures. It therefore does not establish the size or precision of a PSA response estimate for the combined treatment strategies.
3. Trial Design
This was a randomized, open-label, parallel-group phase II trial, registered as NCT01718353 and sponsored by Sanofi. The record lists an enrollment of 63 and a completed status. The recorded start was 2013-03, and primary completion was 2015-08. The intended population was men with metastatic castration-resistant prostate cancer who had not received prior chemotherapy.
Participants were assigned to start with docetaxel plus prednisone or cabazitaxel plus prednisone. The docetaxel arm used docetaxel 75 mg/m^2 intravenously on day 1, with treatment every 3 weeks, and prednisone or prednisolone 10 mg orally daily. The cabazitaxel arm used cabazitaxel 25 mg/m^2 intravenously on day 1, also every 3 weeks, with prednisone or prednisolone 10 mg orally daily. The treatment descriptions specify a switch at cycle 5 for participants whose PSA reduction from baseline was less than 30% at the end of cycle 4. The switch was to the other taxane.
The registry summary explains that, under protocol amendment 3, efficacy analyses combined participants regardless of which taxane they received first. This makes the posted efficacy approach a summary across the switching strategies, rather than a separate account for each initial taxane. The registry record does not report the allocation ratio, details of sequence generation, or a statistical analysis plan. Masking was none; the model was parallel. The record lists additional outcomes including progression-free survival, PSA progression-free survival, response, radiographic and clinical progression-free survival, and overall survival, but does not provide their observed results in the registry record for this analysis.
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 were randomized by Interactive Voice Response System (IVRS) in 2:1 ratio (Treatment A : Treatment B) to receive either Treatment A (Docetaxel + Prednisone) or Treatment B (Cabazitaxel + Prednisone).
Overall Study
| Stage | Docetaxel + Prednisone (Treatment A) | Cabazitaxel + Prednisone (Treatment B) |
|---|---|---|
| STARTED | 41 | 22 |
| Treated | 39 | 22 |
| Treated up to End of Cycle 4 | 32 | 16 |
| Treated From Cycle 5 | 23 | 25 |
| COMPLETED | 29 | 17 |
| NOT COMPLETED | 12 | 5 |
Reasons for not completing this period:
| Reason | Docetaxel + Prednisone (Treatment A) | Cabazitaxel + Prednisone (Treatment B) |
|---|---|---|
| Lost to Follow-up | 0 | 1 |
| Principal Investigator's Decision | 10 | 4 |
| Randomized but not treated | 2 | 0 |
Analysis population for the primary outcome, as defined in the registry: Analysis was performed on all randomized participants.
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 | Docetaxel + Prednisone (Treatment A) | Cabazitaxel + Prednisone (Treatment B) | Total |
|---|---|---|---|---|
| Participants analysed | 41 | 22 | 63 | |
| Age, Continuous | years | 69.9 (SD 7.8) | 69.2 (SD 9.5) | 69.7 (SD 8.4) |
| Sex: Female, Male: Female | Participants | 0 | 0 | 0 |
| Sex: Female, Male: Male | Participants | 41 | 22 | 63 |
6. Primary Endpoint
The registry lists the primary outcome as Percentage of Participants With PSA Response, measured over Baseline, Pre-dose every 3 weeks, 30 days after last treatment administration (End of treatment [EOT]), every 3 months (for 1 year) then every 6 months until PSA progression or study cut-off, whichever was earlier (Maximum duration: 60 weeks).
| Element | Registry entry |
|---|---|
| Result type | Number |
| Measure of spread | not applicable |
| Unit | percentage of participants |
| Endpoint classification | Binary Endpoint |
The primary PSA response measure was the percentage of participants with a decrease in PSA of at least 50% from baseline. The registry defines response as meeting that threshold during the whole treatment period, both before and after a treatment switch. It also describes repeated PSA assessment from baseline through treatment and follow-up, with a maximum duration of 60 weeks.
PSA is a marker used to track prostate cancer activity. A prespecified response threshold turns a continuous measurement into a binary outcome: each participant either meets the response definition or does not. Reporting the percentage meeting that definition can make response frequency easier to interpret than reporting only average PSA changes. The threshold and timing matter, since a response occurring after a switch is included in the stated endpoint, rather than being restricted to the initially assigned drug.
The record also describes primary circulating tumor cell biomarker outcomes: percent androgen receptor nuclear localization and microtubule bundling. These are distinct from the PSA response endpoint and reflect the study’s interest in molecular markers and taxane resistance. The registry record does not report observed results for the PSA endpoint or these biomarker measures. It consequently does not give an observed response percentage, an uncertainty interval, or a comparison estimate for the primary measures.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The registry record describes a randomized study of two taxane-starting strategies that permitted a switch based on early PSA change. The intended decision point was the end of cycle 4, with a switch when the PSA reduction from baseline was less than 30%. The primary PSA outcome used a different threshold: a sustained decrease of at least 50% from baseline at any time during treatment. Keeping those thresholds distinct is important. The first determined when a treatment switch was specified; the second defined the primary PSA response.
The registry summary says efficacy results were combined across participants who began with docetaxel and participants who began with cabazitaxel. Accordingly, the described primary analysis addresses outcomes across the switching approach, not a separate efficacy comparison of the two starting drugs. The record does not report the observed number or percentage of participants meeting the primary PSA response definition. It also does not report an effect estimate, confidence interval, or statistical test for that endpoint. No conclusion about the frequency or precision of the response can be drawn from the information available.
The trial enrolled 63 participants, but this enrollment figure should not be treated as the analyzed denominator for the primary endpoint. The registry states that the analysis population comprised all randomized participants, but does not give the number randomized or an endpoint-specific denominator. Enrollment, randomization, and availability of an endpoint measurement can be different quantities; without the relevant counts, the response percentage cannot be reconstructed.
The primary biomarker outcomes likewise have no observed values in the registry record. The listed secondary outcomes broaden the study’s scope, but their names alone do not establish results. The record does not report results for progression-free survival, PSA progression-free survival, objective response, radiographic progression-free survival, clinical progression-free survival, overall survival, or the other listed PSA response thresholds in the registry record for this analysis.
Any planning illustrations based on an observed effect require an observed effect estimate. The registry entries do not include such an estimate or the numerical outputs of a planning calculation. Any such planning values, when reported separately, should be understood as illustrations rather than evidence of observed power or as a statement of the original trial’s design justification. The registry record does not report the trial’s sample-size justification, interim analyses, or full statistical plan.
9. Statistical Methods Explained
What does the PSA response percentage represent?
For a binary endpoint, each participant is classified according to whether the stated response definition was met. The response percentage is the share of the analysis population classified as responders. Interpreting it depends on having a clear numerator, a clear denominator, and a consistent rule for when measurements count. Here, the response definition was a decrease of at least 50% from baseline, and the registry says that responses during treatment could occur before or after a switch.
The registry record specifies all randomized participants as the primary outcome population, but does not give the response count, denominator, or observed percentage. Without those values, the endpoint cannot be independently recalculated or assigned a numerical uncertainty range. The enrollment of 63 is not a substitute for the endpoint denominator: the registry entries do not say that every enrolled participant was randomized or had an evaluable outcome.
Why do the two PSA thresholds have different roles?
The treatment descriptions use a PSA reduction of at least 30% as the trigger for continuing the initial taxane through the specified decision point; participants who did not reach that reduction were to switch to the other taxane. The primary response endpoint instead required a decrease of at least 50% from baseline. These thresholds answer different questions. One defines a treatment decision within the strategy, while the other defines the primary outcome used to describe response.
Because the primary response could be counted before or after switching, it reflects the overall treatment sequence as described, rather than the effect of the initial drug alone. A response after switching is part of the stated response definition. The registry summary explicitly says that the efficacy data were combined across initial taxanes under protocol amendment 3, so the described analysis does not preserve separate efficacy summaries for each starting group.
What would an uncertainty interval tell a reader?
In general, a confidence interval describes the range of estimates compatible with the observed data under the statistical method used. A narrow interval indicates more precision than a wide interval, while neither interval alone establishes clinical importance. For a response percentage, uncertainty depends on both the observed response count and the denominator. The registry record does not report a confidence interval or the counts needed to assess one for the primary PSA response endpoint.
Likewise, a test of a difference between groups would require a defined comparison and observed outcome data. The registry summary’s combined efficacy analysis does not provide a separate starting-taxane comparison in the registry record. No p-value or comparative effect estimate for the primary endpoint is reported in the registry record. It would not be appropriate to infer one from enrollment or from the safety counts.
How should planning calculations be read?
In general, sample-size calculations use assumptions about the outcome, the effect to detect, the significance level, allocation, and statistical method. The registry entries describe planning illustrations based on a fraction of an observed effect, using a two-sided significance level of 0.05, equal allocation, and a normal approximation. They distinguish participants per arm for non-time-to-event outcomes from total events for time-to-event outcomes. These are planning assumptions, not the trial’s reported design justification, and the registry record does not report that justification.
A planning sample size is not observed power. Observed power is not a substitute for the estimate and its uncertainty; once an outcome is observed, the data are more directly interpreted through the effect estimate, interval, and analysis. The registry entries available do not give numerical planning outputs or the observed primary effect from which such illustrations would be based. A planning illustration therefore cannot fill the gap in the missing primary outcome results.
What can be said about the analysis model?
The registry describes a randomized, parallel-group study with no masking. It states that efficacy analyses were combined across the initial taxanes, but does not report the specific statistical model, test, covariate adjustment, or handling of repeated measurements. The endpoint assessment schedule is described, but an assessment schedule alone does not reveal how the measurements were statistically analyzed. The full analysis plan is not reported in the registry record, so claims about modeling choices or adjustments would be speculative.
General statistical interpretation should therefore remain focused on the design and the endpoint definitions that are reported. The study’s switching rule, the post-switch inclusion in the response definition, and the combined efficacy analysis shape the meaning of any future reported response percentage. Without the observed counts and analysis details, it is not possible to determine the response’s precision or to attribute it separately to either initial taxane.
10. Multiplicity, Missing Data and Analysis Populations
The registry lists several primary outcomes: the percentage of participants with PSA response, percent androgen receptor nuclear localization, and microtubule bundling. It also lists multiple secondary outcomes, including progression and survival measures and additional PSA response thresholds. When a study assesses several outcomes, the chance of at least one apparently notable result can increase if each is tested separately without an adjustment. In general, multiplicity procedures address that issue, but the registry record does not report whether any such procedure was planned or used.
The record identifies the primary PSA analysis population as all randomized participants. It does not report how missing PSA assessments were handled, whether any participants were excluded from the outcome analysis, or whether missing outcomes were imputed. It also does not specify a missing-data strategy for the biomarker or secondary endpoints. The response definition includes observations before and after a switch, but the rules for incomplete follow-up or unobserved measurements are not reported.
The registry summary says efficacy data were combined across participants according to initial taxane, rather than reported separately for those starting docetaxel and those starting cabazitaxel. That is relevant to interpretation of the analysis population and comparison: the described efficacy results represent a combined group, not distinct estimates by starting treatment. The record does not report the number randomized in each initial group or endpoint-specific denominators.
These omissions limit assessment of the analysis, but they do not establish that any particular method was or was not used. The statistical plan, multiplicity handling, and missing-data procedures are not reported in the registry record.
11. Safety Results
The registry reports serious adverse events as affected participants divided by participants at risk.
| Arm | Participants with serious adverse events | Participants at risk | Percentage |
|---|---|---|---|
| Docetaxel + Prednisone (Treatment A) - Throughout | 10 | 27 | 37.0% |
| Cabazitaxel + Prednisone (Treatment B) - Throughout | 8 | 19 | 42.1% |
| Switched Population (Treatment A to B or Treatment B to A) | 9 | 15 | 60.0% |
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 |
|---|---|
| Docetaxel + Prednisone (Treatment A) - Throughout | 26 of 27 |
| Cabazitaxel + Prednisone (Treatment B) - Throughout | 18 of 19 |
| Switched Population (Treatment A to B or Treatment B to A) | 15 of 15 |
Most frequent serious adverse event terms
| Event term | Organ system | Docetaxel + Prednisone (Treatment A) - Throughout | Cabazitaxel + Prednisone (Treatment B) - Throughout | Switched Population (Treatment A to B or Treatment B to A) |
|---|---|---|---|---|
| Febrile neutropenia | Blood and lymphatic system disorders | 3 of 27 | 2 of 19 | 0 of 15 |
| Urinary tract infection | Infections and infestations | 0 of 27 | 2 of 19 | 1 of 15 |
| Sepsis | Infections and infestations | 0 of 27 | 2 of 19 | 0 of 15 |
| Atrial fibrillation | Cardiac disorders | 1 of 27 | 1 of 19 | 0 of 15 |
| Pulmonary embolism | Respiratory, thoracic and mediastinal disorders | 0 of 27 | 1 of 19 | 1 of 15 |
| Hip fracture | Injury, poisoning and procedural complications | 2 of 27 | 0 of 19 | 0 of 15 |
| Bronchitis | Infections and infestations | 1 of 27 | 0 of 19 | 0 of 15 |
| Pneumonia | Infections and infestations | 1 of 27 | 0 of 19 | 0 of 15 |
| Septic shock | Infections and infestations | 1 of 27 | 0 of 19 | 0 of 15 |
| Urosepsis | Infections and infestations | 0 of 27 | 0 of 19 | 1 of 15 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Docetaxel + Prednisone (Treatment A) - Throughout | Cabazitaxel + Prednisone (Treatment B) - Throughout | Switched Population (Treatment A to B or Treatment B to A) |
|---|---|---|---|---|
| Fatigue | General disorders | 18 of 27 | 13 of 19 | 10 of 15 |
| Diarrhoea | Gastrointestinal disorders | 13 of 27 | 12 of 19 | 9 of 15 |
| Nausea | Gastrointestinal disorders | 8 of 27 | 10 of 19 | 7 of 15 |
| Alopecia | Skin and subcutaneous tissue disorders | 9 of 27 | 5 of 19 | 5 of 15 |
| Neuropathy peripheral | Nervous system disorders | 9 of 27 | 6 of 19 | 3 of 15 |
| Decreased appetite | Metabolism and nutrition disorders | 8 of 27 | 4 of 19 | 4 of 15 |
| Abdominal pain | Gastrointestinal disorders | 7 of 27 | 4 of 19 | 4 of 15 |
| Back pain | Musculoskeletal and connective tissue disorders | 5 of 27 | 6 of 19 | 4 of 15 |
| Constipation | Gastrointestinal disorders | 3 of 27 | 6 of 19 | 5 of 15 |
| Vomiting | Gastrointestinal disorders | 3 of 27 | 7 of 19 | 4 of 15 |
Serious events with the highest arm-level rate: febrile neutropenia (11.1%), urinary tract infection (10.5%), sepsis (10.5%), hip fracture (7.4%), urosepsis (6.7%).
The registry reports serious adverse event counts for three reporting groups. In the docetaxel plus prednisone group throughout, 10 of 27 participants were affected by a serious adverse event; in the cabazitaxel plus prednisone group throughout, 8 of 19 were affected. In the switched population, 9 of 15 were affected. These are counts among the stated at-risk group sizes, not efficacy outcomes. The registry also reports other adverse events: 26 of 27, 18 of 19, and 15 of 15 in the respective groups.
The switched population is listed separately from the groups described as receiving one treatment throughout. These group counts should be read according to their registry labels, not combined to create an overall rate. The registry entries do not give additional details about the duration of exposure, event attribution, or a statistical comparison between groups. A difference between raw counts or percentages would not by itself establish a treatment-related difference, especially when the group sizes and treatment histories differ.
The registry lists serious adverse event terms with percentages: febrile neutropenia, 11.1%; urinary tract infection, 10.5%; sepsis, 10.5%; hip fracture, 7.4%; urosepsis, 6.7%; and anaphylactoid reaction, 6.7%. These listed values should be read as registry-reported figures; the registry entries do not specify the denominator for each term in this listing. Death counts are not reported in the registry record.
12. What the Result Does, and Does Not, Mean
The study asks a strategy-level question: what outcomes are observed when participants start with either docetaxel or cabazitaxel and can switch to the other taxane according to an early PSA response threshold? This differs from asking what would happen if every participant remained on the initially assigned drug. The primary response definition also allows a response after switching, so it captures outcomes across the treatment sequence as described.
The registry record provides the treatment rules, primary endpoint definition, and intended analysis population, but does not report the observed primary PSA response result. It also does not report the primary biomarker results or comparative estimates. Consequently, the available information does not show how often the primary response occurred, how precisely it was estimated, or whether outcomes differed by initial treatment. No statement that either strategy succeeded or failed can be supported by the registry entries.
Randomization is a design feature intended to support fair comparisons between assigned groups. However, the described efficacy analysis combines participants by starting taxane, and no separate starting-group results are reported in the registry record. The randomized design therefore does not, by itself, supply a comparison that is absent from the posted results. Nor does a sample-size planning illustration establish observed power or provide an outcome finding.
The safety counts describe participants affected in the registry-defined reporting groups. They do not establish causation, and the listed serious adverse event terms do not substitute for a complete safety comparison. The registry entries do not report deaths or the statistical methods used for safety analyses.
Overall, the record supports a description of the trial’s rationale, treatment sequence, and endpoint definitions. It does not support a numerical conclusion about the primary efficacy outcome or a comparative conclusion about the starting treatments. The distinction between a protocol-defined question and an observed result is central: a clearly specified endpoint does not reveal its result when the outcome data are not reported.
13. Why This Trial Matters Statistically
This trial is statistically notable because the treatment strategy includes a response-guided switch. The initial treatment is not the full strategy: for participants who did not reach the specified PSA reduction after cycle 4, the treatment description calls for switching to the other taxane. An endpoint that counts responses both before and after switching therefore reflects the sequence and decision rule, not simply the initial drug.
The study also distinguishes the PSA threshold used to guide switching from the threshold used to define the primary PSA response. That distinction matters for interpreting the endpoint and for reproducing an analysis. The switch criterion was a reduction of at least 30%, while the primary response definition required a decrease of at least 50%. A reader should not treat these thresholds as interchangeable.
The registry summary says efficacy was combined across initial taxanes under protocol amendment 3. This makes the reported analysis strategy-focused, but means the described primary efficacy result would not separately answer how outcomes varied by starting taxane. Any interpretation needs to follow that stated analysis approach rather than assume a conventional presentation by randomized arm.
Finally, the registry record illustrates a basic reporting issue: outcome definitions and trial design do not replace observed estimates. The primary PSA response and biomarker outcomes are described, but their results are not reported in the registry record. Without counts, estimates, or uncertainty intervals, the statistical question remains unresolved in this record. The distinction is important for researchers assessing what the design intended to measure versus what the posted information allows them to conclude.
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.
A central limitation is that the registry record does not report observed values for the primary PSA response endpoint or the primary circulating tumor cell biomarkers. It provides no response count, percentage, interval estimate, or statistical test for those outcomes. The primary question is therefore defined, but its numerical result cannot be assessed in the registry record.
The efficacy analysis was described as combining participants who began with either taxane. Separate primary efficacy results for the docetaxel-start and cabazitaxel-start groups are not reported in the registry record. The number randomized in each starting group and the endpoint-specific denominators are also not reported. Although enrollment is listed as 63, it does not establish the denominator for any specific endpoint.
The record describes the study as phase II, randomized, open-label, and parallel-group, but does not report the allocation ratio, the full statistical plan, the sample-size justification, interim analyses, or detailed randomization procedures. It does not report methods for missing data or multiplicity across the several primary and secondary outcomes. These omissions prevent evaluation of those aspects of the analysis; they should not be treated as evidence that a particular method was absent.
Safety information is also limited. Counts are presented for the registry-defined treatment and switched groups, but the registry entries do not specify event attribution, exposure duration, or statistical comparisons. The denominator for each listed serious adverse event term is not reported, and death counts are not reported in the registry record. These limitations restrict interpretation of both efficacy and safety without changing the trial’s stated design or outcome definitions.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Early Switch From First-Line Docetaxel/Prednisone to Cabazitaxel/Prednisone and the Opposite Sequence, Exploring Molecular Markers in Men With Metastatic Castration-Resistant Prostate Cancer (mCRPC) — NCT01718353.
- Registry record last updated 2017-11-20; status last verified 2016-08.
- Results first posted 2017-11-20.
- 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
NCT01718353 was a completed randomized, open-label, parallel-group phase II trial sponsored by Sanofi, with an enrollment of 63. It studied men with metastatic castration-resistant prostate cancer who had not received prior chemotherapy. Participants began docetaxel plus prednisone or cabazitaxel plus prednisone, with a switch to the other taxane described for participants who had not achieved a PSA reduction of at least 30% from baseline at the end of cycle 4.
The primary PSA endpoint was the percentage with a decrease of at least 50% from baseline during treatment, including before and after a switch. The registry summary says efficacy analyses combined participants regardless of initial taxane. It also identifies circulating tumor cell biomarkers as primary outcomes. Observed results for these primary outcomes are not reported in the registry record. Safety counts and selected serious adverse event terms are listed, but deaths and detailed safety analysis methods are not reported.