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 limited to the ClinicalTrials.gov record.
1. Trial at a Glance
THOR was a randomized, open-label, parallel phase 3 study in advanced urothelial cancer. The registry reports an enrollment of 629 participants across 4 arms and posts two formal primary-endpoint analyses for overall survival, comparing erdafitinib with chemotherapy in one cohort and with pembrolizumab in another.
| Feature | THOR |
|---|---|
| Trial name | THOR |
| Phase | Phase 3 |
| Condition | Urothelial Cancer |
| Allocation | Randomized |
| Design | Parallel |
| Masking | None |
| Primary purpose | Treatment |
| Enrollment | 629 |
| Arms | 4 |
| Primary endpoint | Overall Survival (OS) |
| Primary endpoint type | Time-to-event |
| Results posted | Yes |
| Outcome measures posted | 21 |
| Statistical analyses posted | 2 |
| Lead sponsor | Janssen Research & Development, LLC |
| Sponsor type | Industry |
| Registry status | Active, not recruiting |
This page focuses on the statistical information explicitly contained in the ClinicalTrials.gov record. The registry data identify two primary OS comparisons and provide a hazard ratio, two-sided 95% confidence interval, and P-value for each.
2. Clinical Question
The trial evaluates overall survival from randomization to death due to any cause in participants with advanced urothelial cancer and selected FGFR gene aberrations. The statistical questions differ by cohort because erdafitinib is compared with different active comparators.
Population
Participants with advanced urothelial cancer and selected fibroblast growth factor receptor (FGFR) gene aberrations.
Intervention
Erdafitinib, with the registry identifying an 8 mg/9 mg regimen in the reported primary analyses.
Comparators
Cohort 1 used chemotherapy consisting of vinflunine 320 mg/m2 or docetaxel 75 mg/m2. Cohort 2 used pembrolizumab 200 mg.
Primary question
Does randomized treatment assignment produce a difference in overall survival between erdafitinib and the specified comparator within each cohort?
3. Trial Design
The registry describes THOR as a randomized, parallel, unmasked phase 3 treatment study. Four arms are listed in the ClinicalTrials.gov record, while the posted primary statistical analyses are organized into two cohort-level comparisons.
Primary OS comparison
- Erdafitinib 8 mg/9 mg
- Comparator: chemotherapy
- Vinflunine 320 mg/m2 or docetaxel 75 mg/m2
- Analysis population: ITT
- Method: log-rank test
Primary OS comparison
- Erdafitinib 8 mg/9 mg
- Comparator: pembrolizumab 200 mg
- Analysis population: ITT
- Method: stratified log-rank test
- Hypothesis type: superiority
4. Endpoints
| Endpoint | Registry definition | Time frame | Type |
|---|---|---|---|
| Overall Survival (OS) | Overall survival was measured from the date of randomization to the date of the participant's death. | From randomization (3 days prior to Cycle 1 Day 1) until death due to any cause (maximum up to 51.7 months) | Time-to-event |
Overall survival is the single registered primary endpoint in the ClinicalTrials.gov record. Because death is the event of interest and follow-up can differ among participants, the endpoint is appropriately treated as a time-to-event outcome rather than as a simple binary proportion.
Why the time origin matters
The registry defines the endpoint from randomization, with the time frame described as beginning 3 days prior to Cycle 1 Day 1. This establishes a common origin for the randomized comparison. Participants who remain alive through their available follow-up do not necessarily have an observed death time; in a conventional survival analysis they contribute follow-up information until censoring.
5. Statistical Methodology
Intention-to-treat analysis
The registry explicitly defines the ITT analysis set as including all randomized participants. Participants in this population were analyzed according to the treatment to which they were randomized.
This preserves the treatment comparison created by randomization. It also means that the primary efficacy analysis is not restricted only to participants who completed treatment exactly as planned.
Log-rank test
The cohort 1 OS comparison was analyzed using a log-rank test. The log-rank test compares the survival experience of two groups over follow-up while accounting for the timing of events and censoring.
Stratified log-rank test
The cohort 2 OS comparison used a stratified log-rank test. Stratification allows a time-to-event comparison to account for prespecified strata when comparing treatment groups. The ClinicalTrials.gov record does not specify the individual stratification variables, so none are added here.
Hazard ratio
The effect measure reported for both primary analyses is the hazard ratio. A hazard ratio compares the estimated instantaneous event rates between treatment groups within the survival-analysis framework.
The hazard ratio is a relative time-to-event measure. It is not an absolute survival probability, a median survival time, or the proportion of participants who benefit.
Two-sided confidence intervals
Both primary analyses report two-sided 95% confidence intervals. The interval describes statistical uncertainty around the estimated hazard ratio under the analysis framework. It should not be interpreted as a range containing the treatment effect for 95% of individual patients.
Superiority hypothesis
Both posted primary analyses are identified as superiority analyses. In this framework, the analysis asks whether the randomized treatment comparison provides evidence of a difference rather than attempting to demonstrate that two treatments are sufficiently close within a prespecified non-inferiority margin.
6. Primary Results: Overall Survival
The registry posts two formal primary-endpoint analyses for overall survival. Both use the ITT analysis set, and both report a hazard ratio with a two-sided 95% confidence interval and a P-value.
6.1 Cohort 1: Erdafitinib vs Chemotherapy
Overall survival hazard ratio
95% CI: 0.48–0.86 · P = 0.0031
Method: log-rank test · Hypothesis: superiority · Analysis: ITT
| Feature | Cohort 1 result |
|---|---|
| Endpoint | Overall Survival (OS) |
| Comparison | Erdafitinib 8 mg/9 mg vs chemotherapy |
| Chemotherapy | Vinflunine 320 mg/m2 or docetaxel 75 mg/m2 |
| Analysis population | Intent-to-Treat analysis set |
| Method | Log-rank test |
| Effect measure | Hazard ratio |
| Estimate | 0.65 |
| 95% CI | 0.48–0.86 |
| P-value | =0.0031 |
| Hypothesis type | Superiority |
The reported hazard ratio of 0.65 means that, within the reported survival-analysis framework, the estimated instantaneous rate of death for participants randomized to erdafitinib was approximately 65% of the corresponding rate in the chemotherapy comparison group. Equivalently, this corresponds to an estimated 35% lower hazard of death relative to the comparator.
The hazard ratio does not mean that 35% of participants avoided death, that survival increased by 35%, or that every participant experienced a 35% reduction in risk. It is a relative time-to-event measure based on the observed follow-up and statistical model.
The 95% confidence interval of 0.48–0.86 communicates uncertainty around the estimated hazard ratio. Because the entire reported interval is below 1, the interval is consistent with a lower estimated hazard in the erdafitinib group under the stated analysis.
The P-value of 0.0031 quantifies the evidence against the null hypothesis within the specified testing framework; it does not measure the magnitude of the treatment effect. Effect magnitude is better represented by the hazard ratio and its confidence interval.
As with other hazard-ratio analyses, interpretation depends on the suitability of the survival-analysis framework, including the relationship between hazards over time. The ClinicalTrials.gov record does not report a proportional-hazards diagnostic or a separate assessment of that assumption.
6.2 Cohort 2: Erdafitinib vs Pembrolizumab
Overall survival hazard ratio
95% CI: 0.92–1.48 · P = 0.2121
Method: stratified log-rank test · Hypothesis: superiority · Analysis: ITT
| Feature | Cohort 2 result |
|---|---|
| Endpoint | Overall Survival (OS) |
| Comparison | Erdafitinib 8 mg/9 mg vs pembrolizumab 200 mg |
| Analysis population | Intent-to-Treat analysis set |
| Method | Stratified log-rank test |
| Effect measure | Hazard ratio |
| Estimate | 1.16 |
| 95% CI | 0.92–1.48 |
| P-value | =0.2121 |
| Hypothesis type | Superiority |
The reported hazard ratio of 1.16 means that, within the reported survival-analysis framework, the estimated instantaneous rate of death for participants randomized to erdafitinib was approximately 16% higher than the corresponding rate in the pembrolizumab group.
This estimate does not establish that erdafitinib causes a 16% higher probability of death, nor does it imply that every participant experienced a 16% higher risk. A hazard ratio is a relative time-to-event measure rather than an absolute probability.
The 95% confidence interval of 0.92–1.48 spans 1. This indicates substantial statistical uncertainty around the estimated relative hazard and includes values corresponding to lower, similar, and higher hazards for erdafitinib relative to pembrolizumab.
The P-value of 0.2121 does not measure the size or clinical importance of the estimated hazard ratio. It quantifies the evidence against the specified null hypothesis under the reported statistical test. A non-small P-value should not be converted into a claim that the two treatments are equivalent or identical.
The comparison was a superiority analysis, not a non-inferiority analysis. Therefore, the absence of a statistically significant superiority result should not be interpreted as formal evidence of non-inferiority or equivalence.
7. Comparing the Two Primary Analyses
| Primary OS comparison | Method | HR | 95% CI | P-value | Hypothesis |
|---|---|---|---|---|---|
| Erdafitinib vs chemotherapy | Log-rank test | 0.65 | 0.48–0.86 | =0.0031 | Superiority |
| Erdafitinib vs pembrolizumab | Stratified log-rank test | 1.16 | 0.92–1.48 | =0.2121 | Superiority |
These estimates should be read as two distinct randomized comparisons, not as one four-arm estimate. The comparator differs between cohorts, and the reported statistical method also differs: a log-rank test is listed for the first comparison and a stratified log-rank test for the second.
8. Serious Adverse Events by Arm
The ClinicalTrials.gov record reports serious adverse events by arm as affected participants divided by participants at risk. These figures are presented exactly as reported in the registry.
| Cohort | Arm | Serious adverse events | Affected / at risk |
|---|---|---|---|
| Cohort 1 | Arm 1A: Erdafitinib 8 mg/9 mg | Serious adverse events | 63 / 142 |
| Cohort 1 | Arm 1B: Chemotherapy | Serious adverse events | 50 / 117 |
| Cohort 2 | Arm 2A: Erdafitinib 8 mg/9 mg | Serious adverse events | 69 / 173 |
| Cohort 2 | Arm 2B: Pembrolizumab 200 mg | Serious adverse events | 81 / 173 |
These are safety counts and denominators, not efficacy results. The ClinicalTrials.gov record does not provide confidence intervals, hypothesis tests, or adjusted comparisons for these serious-adverse-event counts, so no inferential comparison is added here.
9. Statistical Methods Explained
Why was a log-rank test used for overall survival?
Overall survival is a time-to-event endpoint. A participant may die during follow-up or may remain alive when follow-up ends, creating censoring. The log-rank test is designed for comparing survival distributions while incorporating the timing of observed events rather than reducing every participant to a simple alive/dead classification at one arbitrary date.
What does a hazard ratio of 0.65 mean?
A hazard ratio of 0.65 indicates an estimated instantaneous death rate that is 65% as large in the first-listed treatment group as in the comparator under the survival-analysis framework. The complementary description is a 35% lower estimated hazard. It is not a 35-percentage-point increase in survival and does not mean that 35% of patients benefited.
What does a hazard ratio of 1.16 mean?
A hazard ratio of 1.16 indicates an estimated instantaneous death rate 16% higher for the first-listed group relative to the comparator. The confidence interval of 0.92–1.48 shows why the point estimate should not be treated as a precise estimate of a higher hazard: the interval includes 1 as well as values below and above 1.
Why is the confidence interval important?
A point estimate is only one estimate of the treatment effect. The 95% confidence interval communicates how uncertain that estimate is under the statistical framework. In cohort 1, the interval is 0.48–0.86; in cohort 2, it is 0.92–1.48. The widths of these intervals also show that the reported estimates are not exact measurements.
Why does the P-value not measure effect size?
The P-value is a measure of statistical evidence against a null hypothesis under the specified testing procedure. It depends not only on the estimated effect but also on information in the data. Effect size is communicated more directly by the hazard ratio, while the confidence interval communicates uncertainty around that estimate.
Why does the ITT analysis matter?
The registry defines the ITT population as all randomized participants, analyzed according to randomized treatment. This maintains the treatment comparison created by randomization. It also avoids redefining the primary efficacy population based on later treatment exposure or adherence.
Why is this not a non-inferiority analysis?
The registry identifies both primary analyses as superiority hypotheses. Non-inferiority requires a prespecified margin and a different inferential question: whether the treatment is not worse than the comparator by more than that margin. No non-inferiority margin is reported in the ClinicalTrials.gov record, so a non-inferiority conclusion cannot be drawn from the posted superiority analysis.
10. What the Confidence Intervals Tell Us
Cohort 1
The HR estimate is 0.65 with a two-sided 95% CI of 0.48–0.86. The entire reported interval lies below 1, so the interval is consistent with a lower estimated hazard for erdafitinib under this comparison.
Cohort 2
The HR estimate is 1.16 with a two-sided 95% CI of 0.92–1.48. The interval includes 1, so the estimate is compatible with a range of relative hazards that includes no difference.
The two intervals also illustrate why a point estimate should never be interpreted in isolation. An HR of 0.65 may appear more definitive when written alone than it does when accompanied by its uncertainty interval, while an HR of 1.16 does not by itself establish a clinically meaningful increase.
11. Interpreting the P-values Correctly
| Comparison | HR | 95% CI | P-value | Statistical reading |
|---|---|---|---|---|
| Erdafitinib vs chemotherapy | 0.65 | 0.48–0.86 | =0.0031 | The reported superiority test provides evidence against the null under the stated analysis. |
| Erdafitinib vs pembrolizumab | 1.16 | 0.92–1.48 | =0.2121 | The reported superiority test does not provide the same level of evidence against the null under the stated analysis. |
A P-value should always be read together with the effect estimate, confidence interval, endpoint definition, analysis population, and design. A statistically persuasive result does not automatically quantify clinical importance, while a non-small P-value does not prove that treatments are equivalent.
12. Time-to-Event Analysis and Censoring
The registry defines OS from randomization until death due to any cause, with a maximum time frame of up to 51.7 months. This structure naturally creates censored observations: participants who have not died by the end of their observed follow-up have not necessarily completed the event process.
The survival function describes the probability of remaining event-free beyond time t. For overall survival, the event is death from any cause.
The log-rank framework uses the ordering and timing of events across follow-up. This is fundamentally different from simply comparing the proportion of deaths at the end of the study because it uses information accumulated throughout the observation period.
13. Analysis Population and Randomization
The registry explicitly states that the ITT analysis set included all randomized participants and that participants were analyzed according to their randomized treatment. This is one of the most important design features for interpreting the primary efficacy comparisons.
| Concept | THOR registry information |
|---|---|
| Allocation | Randomized |
| Design model | Parallel |
| Masking | None |
| Primary analysis population | Intent-to-Treat |
| ITT definition | All randomized participants |
| Analysis assignment | According to randomized treatment |
Randomization creates the basis for a causal treatment comparison by determining treatment assignment rather than allowing treatment choice to be determined by participant or investigator characteristics. The ITT analysis then retains that original assignment when estimating the primary efficacy comparison.
14. Stratified vs Unstratified Log-Rank Testing
The two posted primary analyses illustrate two related but distinct survival-analysis approaches. Cohort 1 uses a log-rank test, while cohort 2 uses a stratified log-rank test.
Log-rank test
The standard log-rank test compares survival experience between groups across follow-up, accounting for event timing and censoring.
Stratified log-rank test
The stratified version performs the comparison while accounting for predefined strata. The ClinicalTrials.gov record does not identify the specific strata used in cohort 2.
The fact that the methods differ is important. A statistical analysis should be interpreted from the actual method specified for that comparison rather than assuming that every arm in a multi-arm trial was evaluated using one identical test.
15. Multiplicity and the Two Primary Comparisons
THOR has two posted primary-endpoint analyses for the same registered primary endpoint, overall survival, but they address different cohort-level comparisons. One compares erdafitinib with chemotherapy; the other compares erdafitinib with pembrolizumab.
| Feature | Cohort 1 | Cohort 2 |
|---|---|---|
| Endpoint | Overall Survival | Overall Survival |
| First group | Erdafitinib 8 mg/9 mg | Erdafitinib 8 mg/9 mg |
| Comparator | Vinflunine 320 mg/m2 or docetaxel 75 mg/m2 | Pembrolizumab 200 mg |
| Test | Log-rank | Stratified log-rank |
| Hypothesis | Superiority | Superiority |
| HR | 0.65 | 1.16 |
| P-value | =0.0031 | =0.2121 |
16. Interim Analysis, Missing Data, Crossover, and Bayesian Methods
The ClinicalTrials.gov record does not report an interim-analysis procedure, an alpha-spending rule, a non-inferiority margin, a crossover policy, a missing-data or imputation method, or a Bayesian analysis method.
| Design topic | What can be established from the ClinicalTrials.gov record |
|---|---|
| Non-inferiority margin | Not reported; the posted primary analyses are superiority analyses. |
| Crossover | Not reported in the ClinicalTrials.gov record. |
| Factorial design | Not reported; the design model is parallel. |
| Interim analysis | Not reported in the ClinicalTrials.gov record. |
| Missing-data / imputation method | Not reported for the primary OS analysis. |
| Stratification variables | Not reported in the ClinicalTrials.gov record, although cohort 2 used a stratified log-rank test. |
| Bayesian methods | Not reported. |
These omissions are analytically important because each can affect how a trial's evidence should be interpreted. However, adding a conventional method that is not reported would blur the distinction between the registry evidence and general statistical practice.
17. Limitations
- Limited endpoint reporting: the ClinicalTrials.gov record provides formal results for overall survival but do not provide median OS, Kaplan-Meier time-point estimates, event counts for the primary endpoint, or subgroup-specific OS estimates.
- Comparator-specific interpretation: the two primary hazard ratios answer different questions because the comparator changes from chemotherapy in cohort 1 to pembrolizumab in cohort 2.
- Different statistical tests: cohort 1 uses a log-rank test, while cohort 2 uses a stratified log-rank test. The ClinicalTrials.gov record does not provide the stratification variables for cohort 2.
- Multiplicity information is incomplete: two formal primary analyses are posted, but the ClinicalTrials.gov record does not specify how type I error was allocated across the comparisons.
- Open-label design: the registry identifies masking as none. This does not invalidate an objective mortality endpoint, but it is an important design characteristic when considering other outcomes.
- No proportional-hazards assessment is reported: the hazard ratio is a time-to-event effect measure, but the ClinicalTrials.gov record does not report diagnostics or analyses addressing the proportional-hazards assumption.
- Safety inference is limited: serious-adverse-event counts are reported, but no inferential safety comparison is reported in the ClinicalTrials.gov record.
- Unreported design details: the ClinicalTrials.gov record does not specify interim-analysis procedures, missing-data methods, crossover, or Bayesian methods, so these cannot be reconstructed reliably.
18. Why This Trial Matters Statistically
THOR is a useful teaching example because it combines randomized treatment assignment, multiple active comparators, a time-to-event primary endpoint, ITT analysis, hazard ratios, confidence intervals, log-rank testing, and a stratified log-rank comparison within one trial.
| Concept | How it appears in THOR |
|---|---|
| Randomization | The trial uses randomized allocation. |
| Parallel design | The registry identifies a parallel design model with 4 arms. |
| ITT analysis | Both posted primary analyses use all randomized participants according to randomized treatment. |
| Time-to-event endpoint | Overall survival is measured from randomization to death due to any cause. |
| Hazard ratio | Both primary analyses report HR as the effect measure. |
| Confidence interval | Both HRs include two-sided 95% confidence intervals. |
| Log-rank testing | Cohort 1 uses a log-rank test. |
| Stratified log-rank testing | Cohort 2 uses a stratified log-rank test. |
| Superiority testing | Both posted primary analyses are identified as superiority hypotheses. |
| Multiple comparisons | Two formal primary OS analyses are posted for different comparator cohorts. |
| Safety analysis | Serious adverse events are reported by arm. |
19. Statistical Interpretation vs Clinical Interpretation
Statistical interpretation
The cohort 1 analysis reports an HR of 0.65 with a two-sided 95% CI of 0.48–0.86 and P=0.0031. The cohort 2 analysis reports an HR of 1.16 with a two-sided 95% CI of 0.92–1.48 and P=0.2121.
Clinical interpretation
Clinical interpretation requires more than the statistical test. The ClinicalTrials.gov record does not provide median survival, absolute survival probabilities, subgroup results, or other efficacy outcomes needed to characterize the full clinical magnitude of benefit across the trial.
This distinction is particularly important for time-to-event outcomes. A statistically significant hazard ratio does not, by itself, specify how long participants lived, what proportion were alive at a particular time, or how the treatment affected individual patients.
20. Understanding the Two Hazard Ratios
The estimate is below 1, corresponding to an estimated 35% lower hazard of death for erdafitinib relative to the chemotherapy comparator. The 95% CI of 0.48–0.86 quantifies uncertainty around that estimate, and the reported P-value is =0.0031.
The estimate is above 1, corresponding to an estimated 16% higher hazard of death for erdafitinib relative to pembrolizumab. The 95% CI of 0.92–1.48 includes 1, and the reported P-value is =0.2121.
21. Trial Timeline
Trial start
The registry lists March 23, 2018 as the trial start date.
Primary completion
The registry lists April 15, 2024 as the primary completion date.
Active, not recruiting
the ClinicalTrials.gov record identifies THOR as active, not recruiting.
22. What Is and Is Not Reported
The ClinicalTrials.gov record is sufficiently detailed to support a formal discussion of the primary OS analyses, but it does not support reconstruction of every statistical feature that might appear in a full clinical-trial publication.
| Item | Reported in the ClinicalTrials.gov record? |
|---|---|
| Overall survival endpoint definition | Yes |
| Primary OS analyses | Yes |
| Hazard ratios | Yes |
| 95% confidence intervals | Yes |
| P-values | Yes |
| ITT population definition | Yes |
| Log-rank method | Yes |
| Stratified log-rank method | Yes |
| Median overall survival | No |
| Kaplan-Meier estimates | No |
| Primary OS event counts | No |
| Subgroup efficacy estimates | No |
| Non-inferiority margin | No |
| Interim-analysis procedure | No |
| Missing-data / imputation procedure | No |
| Bayesian analysis | No |
This distinction prevents an important statistical error: replacing missing registry information with assumptions based on how similar trials are often analyzed.
23. Related Tutorials
Learn more about the methods used in this trial:
24. Related Statistical Calculators
25. Sources
- ClinicalTrials.gov: THOR — NCT03390504. Official registry record and source for the trial data summarized on this page.
- PubMed: PubMed record associated with the THOR trial publication.
Continue with Clinical Biostats
Build from the statistical methods used in THOR to explore survival analysis, clinical-trial methodology, and statistical calculators.
26. Record Summary
THOR provides a clear example of how a multi-arm randomized phase 3 trial can generate distinct time-to-event comparisons. The ClinicalTrials.gov record identifies overall survival as the registered primary endpoint and provide two formal ITT analyses: erdafitinib versus chemotherapy with a log-rank test, yielding an HR of 0.65 (95% CI 0.48–0.86; P=0.0031), and erdafitinib versus pembrolizumab with a stratified log-rank test, yielding an HR of 1.16 (95% CI 0.92–1.48; P=0.2121).
The central statistical lesson is that these results must be interpreted in their proper comparison-specific context. Hazard ratios describe relative time-to-event effects rather than absolute survival, confidence intervals communicate uncertainty around those estimates, and P-values quantify evidence under a specified testing framework rather than effect magnitude. The ITT population preserves the randomized treatment comparison, while the absence of reported design details such as multiplicity procedures, interim monitoring, missing-data methods, and stratification variables limits how far the statistical interpretation can be extended beyond the information explicitly reported by the registry.