Pazopanib Versus Temsirolimus in Poor-Risk Clear-Cell Renal Cell Carcinoma (RCC): Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Pazopanib Versus Temsirolimus in Poor-Risk Clear-Cell Renal Cell Carcinoma (RCC) (NCT01392183), a randomized phase 2 study. The primary outcome is Progression Free Survival (PFS).

2. Clinical Question

3. Trial Design

This was a randomized, open-label phase 2 trial with a crossover model. The registry records 69 participants enrolled: 35 in the temsirolimus control group and 34 in the pazopanib treatment group for the primary endpoint. The brief summary described enrollment of up to 90 patients, with all participants enrolled at M.D. Anderson. The registry lists the trial as completed.

The listed study dates are a start date of 2012-10-24 and a primary completion date of 2019-09-08. No further account of the enrollment process, follow-up schedule, or reasons for the difference between the planned maximum enrollment and the recorded enrollment is reported in the registry record.

The pazopanib arm description specifies 800 mg by mouth daily. The temsirolimus description specifies 25 mg by vein weekly over 30–60 minutes, with Benadryl before each dose. Both arm descriptions include quality-of-life assessment at baseline and every 8 weeks at clinical evaluation. The primary endpoint description is restricted to the first drug administration in each arm, while the listed study model is crossover. The sequence, timing, and analysis of any crossover are not reported in the registry record, so the primary comparison should be read as the stated first-drug comparison rather than as a complete account of later treatment.

The registry lists overall survival (OS) as a secondary outcome. It does not report the detailed statistical analysis method for either endpoint, allocation concealment, stratification factors, or the trial's original sample-size justification. Those details should not be inferred from the trial's phase or enrollment figures.

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.

First Drug Administration

Reasons for not completing this period:

Second Drug Administration

Analysis population for the primary outcome, as defined in the registry: The ratio is comparing both arms to each other, therefore the data would be identical.

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 Progression Free Survival (PFS), measured over Measured form start of treatment up to 3 years.

PFS measures the time from initiation of treatment until the first recorded disease progression or death from any cause. In this trial, the endpoint description applies to the first drug administration in each arm and states that measurement extended up to 3 years. Progression was defined using RECIST v1.0: a 20% or more increase in the sum of the longest diameters of target lesions, a measurable increase in a non-target lesion, or the appearance of new lesions.

Time-to-event endpoints are used when the timing of an event matters and participants may have different lengths of observation. They can incorporate the ordering and timing of events rather than reducing follow-up to whether an event occurred by one fixed date. The median is a time-point summary of the event-time distribution; it does not describe every participant's course or the uncertainty in a comparison by itself. A hazard ratio is a relative summary of event rates over follow-up, under assumptions about how that relative contrast behaves over time.

The registry reports median PFS of 2.7 months for temsirolimus and 5.2 months for pazopanib, alongside a hazard ratio. The medians and the hazard ratio summarize the data in different ways, so the medians should not be treated as a substitute for the reported comparative analysis.

7. Results Posted in the Registry

• Temsirolimus (Control Group) vs Pazopanib (Treatment Group): hazard ratio 1.36 (95% CI 0.84–2.22) (as reported in the registry).

8. Secondary Efficacy Endpoints

The registry also posts results for secondary outcomes. For each outcome below, the endpoint type, the test applied to the posted summary statistics, the result and its interpretation are given in turn. Secondary endpoints are usually not adjusted for multiple testing, so they support rather than confirm the primary finding.

Overall Survival (OS)

• Endpoint type: Time to event: compared as a hazard ratio.
• Test: Hazard ratio as reported by the sponsor; it was not recalculated.
• Result:
  • Temsirolimus (Control Group) vs Pazopanib (Treatment Group): hazard ratio 1.16 (95% CI 0.70–1.93) (as reported in the registry).
• Interpretation:
  • The 95% confidence interval includes no difference (a ratio of 1), so these data do not show a statistically significant difference between Temsirolimus (Control Group) vs Pazopanib (Treatment Group) and the control. The interval gives the range of effects that remain compatible with the data.

Overall survival is the listed secondary endpoint. Its reported summary has the same broad direction in the median values as the primary endpoint, while the hazard-ratio confidence interval includes 1. Taken together, the endpoints do not give a precise or conclusive estimate of the relative difference. The secondary endpoint adds a view of survival beyond progression, but it does not resolve the uncertainty in the primary comparison.

Secondary outcomes generally carry less weight than the designated primary endpoint because they may be less central to the trial question and may involve additional opportunities to find an apparently notable result. When several outcomes are examined, chance alone can produce an unusual result among them. Adjustments for multiple testing can help control that concern, but whether such adjustment was planned or used is not reported in the registry record.

The registry lists one secondary outcome and reports a hazard ratio, but does not give a p-value, analysis method, or multiplicity strategy. The OS result should therefore be treated as supportive descriptive evidence rather than as an independent confirmatory finding. It should be interpreted with the primary result and its uncertainty, the trial's limited enrollment, and the missing detail about analysis and follow-up.

Secondary outcomes can still contribute useful context, particularly when they address a distinct aspect of the clinical course. Their value depends on prespecified definitions, complete follow-up, and transparent reporting of how analyses were selected and interpreted. Those details are not fully available in the registry record, so the secondary result cannot be used to make stronger claims than its estimate and interval support.

Secondary outcomes registered for this trial, for reference (only those above were recalculated):

• Overall Survival (OS)

9. Statistical Interpretation

10. Statistical Methods Explained

Time-to-event analysis is appropriate when an outcome is defined by how long it takes for an event to occur. PFS is such an outcome: it runs from treatment initiation to progression or death. Participants who have not experienced the event by the end of their observed follow-up may contribute partial information rather than a known event time. This feature is commonly handled by censoring in survival analysis, but the registry does not report the censoring rules or the analysis method used in this trial.

What does a median time summarize?

A median event time is the point at which the estimated event-time distribution reaches its midpoint. It offers an interpretable summary of the time scale, but it does not show the full pattern of events over follow-up. Two groups can have different medians while their event patterns overlap, and the median does not by itself quantify the uncertainty in the between-group contrast. The registry reports full ranges for the medians' associated time summaries, but it does not provide additional detail on how those ranges were calculated.

What does the hazard ratio describe?

A hazard is the event rate at a given time among participants who have not yet experienced the event. A hazard ratio compares hazards between groups over time. Under the usual proportional-hazards interpretation, a single hazard ratio summarizes a relative contrast that is assumed to remain reasonably stable over follow-up. If that assumption does not hold, one overall hazard ratio may not capture changing differences across time. Whether proportional hazards were assessed or assumed in this trial is not reported in the registry record.

The sponsor-reported PFS hazard ratio is 1.36, with a 95% confidence interval from 0.84 to 2.22. The registry's endpoint description states that a value greater than 1 means the treatment group performed better. However, the comparison label reads temsirolimus versus pazopanib, and the model coding is not reported. This makes it important to keep the registry's directional convention distinct from any independent assumption about which group is in the numerator. The estimate and interval can be quoted, but the exact coding cannot be reconstructed from the registry record.

Why does the confidence interval matter?

A confidence interval describes the uncertainty around an estimated effect under the analysis framework. A narrower interval indicates greater precision, while a broader interval leaves more plausible values compatible with the data. For the PFS hazard ratio, the interval includes 1 and extends to values on both sides of it. The estimate therefore does not precisely distinguish a relative advantage in one direction from no difference or a relative advantage in the other direction. The registry does not report a p-value, and one should not invent one from the interval.

Why can event-time data be difficult to summarize?

Participants may have different follow-up durations, and some may leave observation before an event is recorded. The analysis needs to account for this without treating an unobserved event time as though it were known. The registry gives the endpoint definition and timeframe, but it does not state the number of censored participants, follow-up completeness, missing-data handling, or the specific survival estimator. Those omissions limit the ability to independently assess the analysis.

The registry's stated endpoint text refers to an adjusted hazard ratio, but it does not identify adjustment variables or a model. The reported analysis method is not specified. Randomization supports a comparison between assigned groups, but the details needed to evaluate any adjustment or the implementation of randomization are not reported. The results should therefore be interpreted as the registry's reported estimates, not as an independently reconstructed model.

For context, the posted median PFS values are 2.7 months for temsirolimus and 5.2 months for pazopanib. These summaries describe the observed event-time distributions in each group. The comparative hazard ratio combines information differently, using event timing across follow-up. A difference between the medians and the uncertainty in the hazard ratio are not contradictory: they are different summaries, and their interpretation depends on the full event-time data and analysis assumptions.

11. Confidence Intervals and Precision

The PFS hazard ratio is reported as 1.36, with a 95% confidence interval from 0.84 to 2.22. The interval is broad enough to include the no-difference value of 1 and values on either side. It therefore leaves substantial uncertainty about the direction and magnitude of the relative contrast. The registry does not report a p-value for this estimate.

The median PFS values are 2.7 months for temsirolimus and 5.2 months for pazopanib. The registry gives ranges of 1.2 to 24.6 months and 0.4 to 34.5 months, respectively. These ranges indicate that observed times varied considerably, but a range is not a confidence interval and does not directly express the precision of the median or the treatment comparison. No confidence interval for either median is reported in the registry record.

For OS, the reported hazard ratio is 1.16, with a 95% confidence interval from 0.7 to 1.93. That interval also includes 1 and values on either side. Its uncertainty means the secondary comparison is not precise about the direction of the relative contrast. The median OS values and their ranges likewise describe observed times, not the uncertainty in a comparative effect.

Confidence intervals are compatible with a range of effects under the analysis assumptions; they do not state the probability that a particular value is true. The registered enrollment and group sizes provide context for the amount of information available, but precision also depends on event counts, follow-up, and the analysis. Event counts for the efficacy analyses are not reported in the registry record.

12. Planning a Similar Trial: Sample Size

This is a planning illustration, not a re-evaluation of the original trial. It asks: if a new study wanted to detect a difference like the one observed, or a smaller one, how large would it need to be? It is deliberately not “observed power” of the finished trial, which is not a meaningful quantity.

The planning entries are illustrations based on the observed effect, not the trial's original design calculations. For these time-to-event outcomes, the entries give the total number of events needed, not participants per arm. The planning assumptions are a two-sided significance level of 0.05, equal allocation between the two arms, and a normal approximation. The effect to detect is set to the stated fraction of the observed effect. The registry's own original design assumptions and sample-size justification are not reported.

The 80% power column means the illustrative event count that would give an 80% chance of detecting the specified effect if the planning assumptions and effect were correct. The 90% power column expresses the corresponding event count for a higher chance of detection. These are planning targets, not guarantees about a future study. They do not say how likely the observed result is to be true, and this is not observed power.

Rows planning for 100%, 75%, and 50% of the observed effect use progressively smaller effects. Smaller effects are harder to distinguish from random variation, so the planning illustration requires more events to detect them at the same stated power. For example, for PFS the entries rise from 333 total events for 80% power at 100% of the observed effect to 1,329 total events at 50% of the observed effect. At 90% power, the corresponding entries are 445 and 1,779 total events. These are event counts, not participant counts.

Such illustrations help show how strongly planning requirements depend on the assumed effect size. They should not be compared directly with the enrolled participant count as though enrollment and required events were interchangeable. The actual event counts for the efficacy analyses are not reported in the registry record, and no conclusion about whether a planned target was reached can be drawn from these entries.

13. How the Sample Size Is Derived

Power is the probability that a study of a given size rejects the null hypothesis when a specific true effect exists. It depends on four things: the effect to detect, the variability of the outcome, the significance level (here a two-sided α of 0.05, so z_1−α/2 = 1.960) and the desired power (z_1−β = 0.842 for 80% and 1.282 for 90%).

Formula

d is the total number of events needed (Schoenfeld's formula) with 1:1 allocation and proportional hazards.

Worked calculation for this trial

1. Hazard ratio HR = 1.360, so ln(HR) = 0.3075.
2. d = 4 × (1.96 + 0.842)² / [ln(1.360)]² = 332.1, rounded up to 333 events in total for 80% power.

The smaller-effect rows in the table above repeat the same calculation with the effect multiplied by 0.75 and 0.5 (for ratios, applied to the logarithm of the ratio).

R code

alpha <- 0.05
z_a   <- qnorm(1 - alpha / 2)          # two-sided
hr <- 1.36                              # observed hazard ratio
events_needed <- function(power, frac = 1) ceiling(round(4 * (z_a + qnorm(power))^2 / log(hr^frac)^2, 6))   # Schoenfeld, 1:1 allocation
for (f in c(1, 0.75, 0.5))
  cat(sprintf("%3.0f%% of observed effect: events = %s (80%% power), %s (90%% power)\n", 100 * f,
              format(events_needed(0.80, f), big.mark = ","), format(events_needed(0.90, f), big.mark = ",")))

# Simulation: given d total events under proportional hazards, events in the treatment arm are Binomial(d, hr / (1 + hr)).
# The score (log-rank type) statistic is (D1 - d / 2) / sqrt(d / 4).
set.seed(1392183)
d    <- events_needed(0.80)
reps <- 20000
D1 <- rbinom(reps, d, hr / (1 + hr))
z  <- (D1 - d / 2) / sqrt(d / 4)
cat(sprintf("Simulated power with %s events: %.3f (%d replicates)\n", format(d, big.mark = ","), mean(abs(z) > z_a), reps))

Output from running the code

100% of observed effect: events = 333 (80% power), 445 (90% power)
 75% of observed effect: events = 591 (80% power), 791 (90% power)
 50% of observed effect: events = 1,329 (80% power), 1,779 (90% power)
Simulated power with 333 events: 0.795 (20000 replicates)

The simulation uses the fact that, with d events in total and proportional hazards, the number of events in the treatment arm is binomial. It is an approximation that conditions on the total number of events, and it should land close to the target power.

14. Analyses Reported by the Sponsor

The registry's reported PFS analysis is a hazard ratio of 1.36 with a 95% confidence interval from 0.84 to 2.22. No p-value or analysis method is reported. The statistical display uses the sponsor's reported hazard ratio rather than replacing it with an independently recalculated comparison. The registry records no discrepancy between the sponsor result and the posted summary statistics.

A simple recalculation from posted summary statistics would be unadjusted and would not reproduce an adjusted time-to-event model. It cannot recover unreported covariates, event times, censoring, or model choices. Where a sponsor's own analysis is available, that analysis takes precedence over a recalculation for describing the trial's reported result. In this case, the sponsor's reported estimate and interval are the central comparative figures.

The registry describes an adjusted hazard ratio but does not name the adjustment method or variables. It also does not specify the hazard-ratio coding. The comparison label and the stated directional convention should therefore be read together rather than assuming a numerator from the ordering of group names alone. The interval's inclusion of 1 remains the key qualification: the reported estimate is not precise enough to rule out no relative difference.

15. Multiplicity, Missing Data and Analysis Populations

The registry identifies PFS as the primary endpoint and OS as a secondary outcome. It does not report whether the trial used a formal strategy to control multiplicity across outcomes, analyses, or time points. When multiple hypotheses are examined, the chance of at least one apparently unusual result can increase. Statistical adjustment or a prespecified hierarchy can address that issue, but neither approach should be assumed without a report.

The registry does not report the planned analysis populations, such as whether the primary analysis used all randomized participants, participants who received treatment, or another defined set. It also does not give participant flow by analysis population, exclusions after randomization, or reasons for missing outcome data. These details matter because removing participants or handling missing observations differently can affect the comparability created by randomization.

For time-to-event analyses, censoring and follow-up completeness are especially relevant. The registry gives the endpoint definitions and timeframes but does not report censoring rules, numbers censored, loss to follow-up, or how missing dates or assessments were handled. It also does not report whether the proportional-hazards assumption was assessed. These omissions prevent a full assessment of how the reported estimates depend on follow-up and model assumptions.

Although the listed trial model is crossover, the primary endpoint description focuses on the first drug administration in each arm. The crossover sequence, timing, and any effect on the analysis are not reported in the registry record. The registry also does not report interim analyses, stopping rules, or the original statistical analysis plan. These absences do not prove that such procedures were not used; they mean their details are unavailable in the registry record.

16. 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% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: dyspnea (6.0%), edema (6.0%), nausea (4.0%), pneumonia (4.0%), acute kidney injury (3.6%).

The registry reports serious adverse events affecting 15 of 50 participants at risk in the temsirolimus group and 10 of 55 at risk in the pazopanib group. Other adverse events affected 35 of 50 and 33 of 55, respectively. Deaths are reported as 32 in the temsirolimus group and 31 in the pazopanib group. These are the registry's counts and should not be reinterpreted as rates using a different denominator.

The listed serious-event terms include dyspnea and edema at 6.0% each, nausea and pneumonia at 4.0% each, acute kidney injury at 3.6%, and non-cardiac chest pain at 2.0%. The registry does not provide enough detail to establish event attribution, exposure-adjusted rates, recurrence, timing, or severity grading. The number at risk differs from the primary endpoint group sizes, and the relationship between those safety denominators and the randomized groups is not explained in the registry record.

These figures are descriptive safety summaries. Differences in counts alone do not establish that one treatment caused more or fewer events, particularly without details about exposure duration, definitions, and follow-up.

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

The results describe a randomized comparison of first-treatment PFS and a secondary OS outcome in poor-risk clear-cell renal cell carcinoma. The recorded PFS medians were 2.7 months for temsirolimus and 5.2 months for pazopanib. The sponsor-reported PFS hazard ratio was 1.36, with a 95% confidence interval from 0.84 to 2.22. Because the interval includes 1 and extends in both directions around it, the comparative estimate remains uncertain.

The registry's own directional description says a hazard ratio greater than 1 favors the treatment group, but the comparison label is written as temsirolimus versus pazopanib. The coding and analysis method are not reported. The estimate should therefore be quoted with that ambiguity rather than used to make an unqualified directional claim. Median values describe each group's event-time summary; they do not resolve the uncertainty in the hazard-ratio comparison.

The OS comparison also has an interval that includes 1, and its analysis details are limited. It should not be treated as proof that the groups differ or are equivalent. Failure to establish a precise difference is not evidence that the treatments have identical effects. Conversely, an observed difference in medians does not alone establish a reliable treatment effect.

The results do not establish what would occur in every patient, how outcomes would compare in populations not represented by the trial, or how safety differs after accounting for exposure and follow-up. The registry record does not report the full eligibility criteria, analysis population, censoring details, or original statistical plan. Those limits matter when interpreting a small randomized phase 2 study with broad confidence intervals.

These are statistical interpretations of registry-reported findings, not treatment recommendations. Decisions about care require clinical context beyond these summary estimates.

18. Why This Trial Matters Statistically

This trial illustrates why a reported median and a comparative effect estimate should be read together but not treated as interchangeable. The medians offer an accessible summary of time to progression or death, while the hazard ratio uses the event-time comparison across follow-up. The confidence interval supplies essential context: the PFS estimate is compatible with a range of relative effects, including no difference.

It also demonstrates how reporting details affect interpretation. The registry gives the hazard ratio and interval but not the model method, adjustment variables, p-value, or coding. Its written direction rule and comparison label are not straightforwardly aligned. Transparent specification of the contrast and analysis would make the direction easier to interpret without relying on assumptions.

The enrollment figures show that the recorded trial included 69 participants, with 35 and 34 in the primary endpoint groups. The original sample-size justification is not reported. The separate planning illustrations emphasize that time-to-event study planning depends on the effect size and the number of events, not simply the number of people enrolled.

Finally, the crossover designation alongside a first-drug primary comparison makes treatment sequence and analysis details important. The registry does not report those details. This is a useful reminder that design labels, endpoint definitions, analysis methods, and follow-up procedures all contribute to how a clinical result can be understood.

19. 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.

Several trial-specific limitations constrain interpretation. Enrollment was 69, although the brief summary described enrollment of up to 90. The registry does not explain the reason for the final enrollment or provide the original sample-size justification. The planning illustrations are not the trial's design calculations and cannot establish whether the study was planned to detect a particular effect.

The listed model is crossover, but the primary endpoint description compares first drug administration in each arm. The registry does not report the crossover sequence, timing, treatment after crossover, or whether later treatment affected follow-up or analyses. This limits understanding of the overall treatment experience beyond the first-drug comparison.

The sponsor-reported hazard ratios are available, but the analysis methods, adjustment factors, coding direction, p-values, and proportional-hazards assessment are not. The registry does not report event counts for the efficacy analyses, censoring details, missing-data handling, or analysis populations. Without these, the estimates cannot be independently reproduced or fully assessed for sensitivity to assumptions.

The safety denominators of 50 and 55 do not match the primary endpoint group sizes of 35 and 34, and the registry does not explain the denominator definitions or their relationship to randomized participants. The summary also lacks exposure-adjusted safety measures and detailed event attribution. Finally, eligibility details beyond the poor-risk clear-cell disease description are not reported in the registry record, limiting assessment of how broadly the findings apply.

20. Related Tutorials

21. Related Statistical Calculators

22. Sources

• ClinicalTrials.gov: Pazopanib Versus Temsirolimus in Poor-Risk Clear-Cell Renal Cell Carcinoma (RCC) — NCT01392183.
• Registry record last updated 2021-09-20; status last verified 2021-08.
• Results first posted 2021-09-20.
• 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.

23. Record Summary

The registry describes a completed randomized, open-label phase 2 crossover trial of pazopanib versus temsirolimus in poor-risk clear-cell renal cell carcinoma. It records 69 participants enrolled, with 35 in the temsirolimus group and 34 in the pazopanib group for the primary endpoint. The primary endpoint was PFS during first drug administration, with OS listed as a secondary outcome.

Median PFS was 2.7 months with temsirolimus and 5.2 months with pazopanib. The reported PFS hazard ratio was 1.36, with a 95% confidence interval from 0.84 to 2.22. The interval includes 1, leaving the relative comparison uncertain. The registry does not report the analysis method, p-value, original sample-size justification, or full crossover and missing-data details.