A Trial to Evaluate Efficacy and Safety of Lenvatinib in Combination With Everolimus in Subjects With Unresectable Advanced or Metastatic Non Clear Cell Renal Cell Carcinoma (nccRCC) Who Have Not Received Any Chemotherapy for Advanced Disease: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for A Trial to Evaluate Efficacy and Safety of Lenvatinib in Combination With Everolimus in Subjects With Unresectable Advanced or Metastatic Non Clear Cell Renal Cell Carcinoma (nccRCC) Who Have Not Received Any Chemotherapy for Advanced Disease (NCT02915783), a na phase 2 study. The primary outcome is Objective Response Rate (ORR).

2. Clinical Question

The central statistical question is descriptive: how often did participants in this treatment group meet the stated response criteria? The record identifies objective response rate (ORR) as the primary objective and reports that the FAS included participants who received at least 1 dose of the study drugs. It does not report the numerical ORR estimate, the number of participants with a confirmed response, or the 95% confidence interval. The response result therefore cannot be characterized from the registry record.

The study addressed a defined clinical population: people with unresectable advanced or metastatic nccRCC who had not received chemotherapy for advanced disease. It was a Phase 2 study conducted at multiple centers. Because there was no comparator group, the primary question is not whether the combination outperformed another treatment or usual care. A single-arm response estimate can describe outcomes in the enrolled treatment group, but it cannot by itself establish how those outcomes compare with what would have occurred under another treatment.

The registry also lists progression-free survival and overall survival as secondary outcomes. Numerical results for those outcomes are not reported in the registry record. The record therefore defines the questions the study set out to address more clearly than it reports the answers.

3. Trial Design

This was a Phase 2, multicenter, single-arm study of lenvatinib combined with everolimus in participants with unresectable advanced or metastatic nccRCC who had not received chemotherapy for advanced disease. The registry lists enrollment as 41 and status as completed. The listed study start was 2017-02-20, and primary completion was 2021-11-02.

The treatment group received initial doses of lenvatinib 18 mg/day and everolimus 5 mg/day. The registry describes the drugs as oral and taken in immediate succession once a day. The arm description is incomplete in the registry record, so further details about dosing instructions should not be inferred from it.

There was no allocation to different groups and no masking: the record identifies the model as single group, allocation as not applicable, and masking as none. In practical terms, the primary analysis describes outcomes in participants receiving the study combination rather than a contrast between randomized treatment groups. The registry does not report a separate control arm or a like-for-like comparison.

The study description identifies pretreatment, treatment, and posttreatment phases. The primary outcome was investigator-assessed ORR, with RECIST v1.1 response criteria. The primary outcome timeframe is stated as running from the first dose to the first documentation of disease progression or death, whichever occurred first, up to approximately 3 years 9 months. Progression-free survival and overall survival are listed as secondary outcomes.

The registry's enrollment figure does not establish the analysis denominator for ORR. The described FAS included participants who received at least 1 dose of the study drugs, but the number in that population is not reported in the registry record. The number assessed for the endpoint and the handling of participants without an evaluable response are also not reported.

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: A total of 41 participants were enrolled (signed inform consent form) and screened, of which 10 were screen failures and 31 participants received the study treatment.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: The FAS included participants who received at least 1 dose of the study drugs.

5. Baseline Characteristics

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

Population: The full analysis set (FAS) included participants who received at least 1 dose of the study drugs.

6. Primary Endpoint

The registry lists the primary outcome as Objective Response Rate (ORR), measured over From the date of the first dose of study drug to the date of the first documentation of disease progression or death, whichever occurred first (up to approximately 3 years 9 months).

Objective response rate is the percentage of participants whose confirmed best overall response was complete response or partial response. The registry says response was assessed by the investigator using RECIST v1.1. A complete response required disappearance of all target and non-target lesions other than lymph nodes, with pathological lymph nodes reduced to a short axis < 10 mm. A partial response required at least a 30% decrease in the sum of target-lesion diameters relative to the baseline sum.

ORR is used as a summary of tumor response: it counts participants meeting a specified response threshold rather than describing every change in tumor measurements. Requiring confirmation is intended to distinguish a confirmed response from an unconfirmed assessment. As a general statistical point, a percentage is easier to interpret when its numerator, denominator, assessment rules, and uncertainty are also clear.

The registry identifies the FAS as participants who received at least 1 dose of the study drugs and specifies a 95% confidence interval for the endpoint. However, it does not report the response count, numerical ORR, analysis denominator, or confidence interval. The endpoint definition is available, but the magnitude and precision of the observed response estimate cannot be judged from this record.

The stated timeframe runs from the first dose to the first documentation of progression or death, whichever occurred first, up to approximately 3 years 9 months. That wording is part of the registry outcome definition; the actual follow-up duration for individual participants is not reported in the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The primary endpoint is a binary response outcome at the participant level: each participant either meets the confirmed complete or partial response definition, or does not. The registry expresses the endpoint as a percentage of participants. In general, a proportion is calculated from the number meeting the event definition divided by the relevant analysis population. The response count and denominator are not reported in the registry record, so the numerical proportion cannot be reconstructed.

The endpoint uses RECIST v1.1 and investigator assessment. As described in the registry, complete response requires disappearance of target and non-target lesions, with a specific condition for pathological lymph nodes. Partial response requires at least a 30% decrease in the sum of target-lesion diameters from baseline. These criteria define which observations count as response; they do not themselves state how many participants responded. The record says the best overall response must be confirmed.

The registry specifies a 95% confidence interval for ORR. In general, a confidence interval communicates the precision of an estimate under a chosen statistical method and its assumptions. The method used to calculate the interval is not reported in the registry record, and neither are the interval limits. Different interval procedures can behave differently, especially when a proportion is based on a modest number of observations or is close to an endpoint such as zero or one. Without the selected method and observed result, precision cannot be assessed.

The analysis population is described as the FAS, including participants who received at least 1 dose of the study drugs. This definition indicates that treatment exposure is relevant to population membership. The size of the FAS is not reported, and the record does not specify whether anyone enrolled failed to enter it. It also does not state how participants with missing, unevaluable, or unconfirmed response assessments were classified. In general, such rules matter because they determine the denominator and can affect an estimated response proportion.

The record lists 41 as enrollment. Enrollment and analysis population size are not interchangeable: participants may not all contribute to a particular endpoint, depending on the analysis definition and available assessments. The registry does not report the ORR denominator, so the enrollment figure should not be substituted for it.

There is no randomized allocation in this single-group design. General statistical interpretation of a one-group outcome focuses on estimating the outcome within that group. It does not provide a randomized treatment contrast, and adjustment for baseline differences between treatment groups is not applicable as a between-group comparison in this record. The allocation and masking fields indicate that no randomized comparison or masking was used.

The registry lists progression-free survival and overall survival as secondary outcomes. These are time-to-event outcomes in general: their analysis typically concerns the time until a defined event, while accounting for participants whose event has not been observed by the end of follow-up. The event definitions, censoring rules, analytical methods, estimates, and confidence intervals for these outcomes are not reported in the registry record. No survival-curve or hazard-based result should be inferred from the endpoint names alone.

The record does not report the statistical analysis plan, sample-size justification, or any interim analyses. It lists no analyses in the record. That absence does not establish what may have been planned or conducted outside the registry entry; those details are not reported in the registry record.

A planning illustration associated with the posted material is distinct from the original trial design. The stated illustration assumptions are a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation, with the effect to detect expressed as a stated fraction of the observed effect. For time-to-event outcomes, the illustration concerns total events; for other outcomes, it concerns participants per arm. These are hypothetical planning assumptions, not observed power, and they do not turn this single-arm trial into a randomized two-arm study. The numerical illustration outputs and the effect estimate used for them are not reported in the registry record.

As a general concept, over-dispersion refers to variability greater than a statistical model expects. It can make standard errors and confidence intervals too small if ignored. The listed primary endpoint, however, is a participant-level binary proportion, and the registry does not report an over-dispersion model or an analysis addressing it. It would be inappropriate to assume that such a method was used.

Multiplicity arises when several outcomes or analyses are tested and the chance of a false-positive finding across them may increase. The record lists a primary outcome and secondary outcomes, but does not report a multiplicity adjustment, testing hierarchy, or confirmatory status for secondary analyses. Therefore, the interpretation of any secondary findings cannot be assessed for multiplicity from this record; in any case, numerical secondary results are not reported.

10. Exact Estimates for Each Arm

No two-arm comparison is shown for this trial, but each arm's result can still be summarized with exact interval estimates computed from the posted counts. The Clopper-Pearson interval is exact and conservative; the Wilson interval is a common closer-to-nominal alternative; the Bayesian credible interval uses a uniform Beta(1, 1) prior. For small groups the three can differ noticeably.

R code and output

arm    <- c("Lenvatinib 18 mg/Day + Everolimus 5 mg/Day")
n      <- c(31)
events <- c(8)
for (i in seq_along(n)) {
  ci <- binom.test(events[i], n[i])$conf.int          # Clopper-Pearson exact interval
  cr <- qbeta(c(0.025, 0.975), 1 + events[i], 1 + n[i] - events[i])   # Bayesian, uniform Beta(1,1) prior
  wi <- (function(x, n) { p <- x / n; z <- qnorm(0.975); d <- 1 + z^2 / n
    c((p + z^2 / (2 * n) - z * sqrt(p * (1 - p) / n + z^2 / (4 * n^2))) / d, (p + z^2 / (2 * n) + z * sqrt(p * (1 - p) / n + z^2 / (4 * n^2))) / d) })(events[i], n[i])
  cat(sprintf("ARM|%s|%d|%d|%.1f|%.1f|%.1f|%.1f|%.1f|%.1f|%.1f\n", arm[i], n[i], events[i], 100 * events[i] / n[i],
              100 * ci[1], 100 * ci[2], 100 * wi[1], 100 * wi[2], 100 * cr[1], 100 * cr[2]))
}

ARM  Lenvatinib 18 mg/Day + Everolimus 5 mg/Day  31  8  25.8  11.9  44.6  13.7  43.2  13.7  43.4

11. Multiplicity, Missing Data and Analysis Populations

The registry identifies ORR as the primary outcome and lists progression-free survival and overall survival as secondary outcomes. It does not report a statistical testing hierarchy, multiplicity adjustment, or whether the secondary outcomes were intended to support formal confirmatory claims. In general, evaluating multiple outcomes can increase the chance of at least one apparently notable result by chance; a prespecified strategy can help control or interpret that issue. No such strategy is reported in the registry record.

The registry defines the FAS as participants who received at least 1 dose of the study drugs. It does not give the size of that population, the endpoint denominator, or the number of participants with missing or unevaluable response assessments. The handling of missing response data, including whether participants without a documented response were counted as nonresponders or treated another way, is not reported in the registry record.

The record does not describe missing-data procedures for progression-free survival or overall survival, including censoring rules or follow-up completeness. It also does not report the statistical analysis plan or any interim analyses. Those omissions prevent assessment of whether analysis decisions were prespecified and how incomplete outcome information was handled. They do not establish that any particular method was or was not used outside the registry record.

12. 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 0% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: nausea (9.7%), vomiting (9.7%), pneumonia (6.5%), cancer pain (6.5%), malignant neoplasm progression (6.5%).

For the listed lenvatinib and everolimus group, the registry records 31 participants at risk for serious adverse events and 12 affected. For other adverse events, it records 31 at risk and 31 affected. The record also lists 21 deaths. These are descriptive figures for the treatment group, not comparisons against a control group.

The listed serious adverse-event terms and percentages are nausea, 9.7%; vomiting, 9.7%; pneumonia, 6.5%; cancer pain, 6.5%; malignant neoplasm progression, 6.5%; and cardiac arrest, 3.2%. The registry record does not provide further detail about event timing, duration, severity beyond the serious-event classification, or attribution to study treatment. It also does not state the time window or cause information associated with the death count.

In general, an adverse-event count or percentage describes events recorded under the study's reporting definitions; it does not by itself establish that treatment caused an event. Nor does a count without a comparator estimate the difference in safety between treatments. The percentages should be read as registry-reported figures, not as evidence of comparative risk. The record does not provide enough detail to determine whether participants experienced more than one listed event or how repeated events were handled.

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

The registry record establishes that a multicenter Phase 2 single-arm study was conducted in participants with unresectable advanced or metastatic nccRCC who had not received chemotherapy for advanced disease. It specifies the combination and the primary response definition. It also lists secondary survival outcomes and descriptive adverse-event figures. Those details describe the study's scope and recorded measures.

The record does not report the numerical ORR, response count, denominator, or 95% confidence interval. It therefore does not show how often participants met the response criteria or how precisely that proportion was estimated. Numerical results for progression-free survival and overall survival are also not reported in the registry record. The absence of these estimates from the record should not be interpreted as an estimate of zero or as evidence that no events occurred.

Even if a single-arm response estimate were available, it would describe outcomes in the treated group rather than establish a causal treatment effect. Without a concurrent comparison group, differences from an external benchmark could reflect differences in patient characteristics, assessment, follow-up, or other factors. The registry record does not provide a randomized comparison.

The safety figures likewise describe reported events in the listed group. They do not determine whether an event was caused by treatment, and they do not quantify how the event rate compares with another treatment. The record does not report the relevant attribution or time-window details.

These limits are about what can be concluded from the registry record, not medical guidance. The result information available supports describing the design, outcome definitions, and recorded safety counts. It does not support a conclusion about the magnitude of efficacy, comparative benefit, or comparative safety.

14. Why This Trial Matters Statistically

This trial is statistically notable for the way its design shapes the questions it can answer. It is a single-arm Phase 2 study, so its central efficacy outcome is a response proportion within one treated group. That kind of estimate can be informative as a description of observed responses, but a treatment contrast requires a comparator. The registry does not describe one.

The primary endpoint is defined in operational detail: investigator-assessed RECIST v1.1, confirmed best overall response, and specified complete- and partial-response criteria. Such definitions help make clear what counts as an outcome. Yet interpretation also depends on results that are absent from the registry record: the response count, denominator, numerical percentage, and confidence interval. A precise outcome definition cannot substitute for the estimate and its uncertainty.

The record also illustrates why the analysis population matters. Enrollment is recorded as 41, while the FAS is defined by receiving at least 1 dose. Since the size of the FAS and the endpoint denominator are not reported, enrollment alone cannot establish how many participants contributed to ORR. Missing or unevaluable assessments and their handling are also unspecified.

Finally, a completed trial record is not necessarily a complete statistical report. The registry identifies secondary outcomes and lists safety figures, but does not provide numerical survival results or a statistical analysis plan. For researchers, this distinction is important: study design and endpoint definitions clarify what was intended to be measured, while estimates, uncertainty, analysis populations, and prespecified methods are needed to assess what the data show.

15. 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 main trial-specific limitation for interpreting efficacy is that the registry record does not report the primary ORR estimate or its 95% confidence interval. It also omits the number of confirmed responses and the analysis denominator. Although the record defines the FAS as participants who received at least 1 dose, the FAS size is not reported. Enrollment of 41 cannot be assumed to be the ORR denominator.

The study had a single group and no comparator. This prevents a direct randomized comparison and limits causal interpretation of any observed outcome. The registry also does not report the statistical analysis plan, the method used to calculate the confidence interval, a sample-size justification, or interim analyses. The response-assessment process is described as investigator-based, but further information about review procedures is not reported in the registry record.

The registry lists progression-free survival and overall survival as secondary outcomes but does not report their numerical results, event counts, or analytical details. The rules for missing or unevaluable response assessments, follow-up completeness, and censoring for time-to-event outcomes are not reported. The listed timeframe for the primary outcome does not reveal the actual follow-up received by participants.

Safety interpretation is also limited. The record gives affected counts, a death count, and percentages for listed serious adverse-event terms, but does not report event attribution, timing, duration, or the time window underlying the death count. With no control group, these figures do not support comparative safety estimates. These are limitations of the information reported in the registry record; they do not establish what may have been documented elsewhere.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: A Trial to Evaluate Efficacy and Safety of Lenvatinib in Combination With Everolimus in Subjects With Unresectable Advanced or Metastatic Non Clear Cell Renal Cell Carcinoma (nccRCC) Who Have Not Received Any Chemotherapy for Advanced Disease — NCT02915783.
• Registry record last updated 2023-01-17; status last verified 2021-06.
• Results first posted 2020-07-13.
• 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.

19. Record Summary

The record describes a completed multicenter Phase 2 single-arm study of lenvatinib plus everolimus in participants with unresectable advanced or metastatic nccRCC who had not received chemotherapy for advanced disease. Enrollment is listed as 41. The listed initial doses were lenvatinib 18 mg/day and everolimus 5 mg/day.

ORR, assessed by the investigator using RECIST v1.1, was the primary outcome. The FAS included participants who received at least 1 dose. Progression-free survival and overall survival were secondary outcomes. Numerical efficacy results and the ORR confidence interval are not reported in the registry record. The record lists serious and other adverse-event figures for the treatment group, but does not provide a comparator or further event attribution details.