Checkpoint Blockade Immunotherapy Combined With Stereotactic Body Radiation in Advanced Metastatic Disease: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Checkpoint Blockade Immunotherapy Combined With Stereotactic Body Radiation in Advanced Metastatic Disease (NCT02843165), a randomized phase 2 study. The primary outcome is Objective Response Rate.

2. Clinical Question

The comparison concerns response assessed at a specified time, rather than a continuous change score or a time-to-event endpoint. The registry describes the study purpose as determining whether adding SBRT to CBI would improve response compared with CBI alone. The posted results estimate the difference between the groups in the number and proportion of participants meeting the objective-response definition. They do not, by themselves, establish how the result would generalize beyond the participants and study conditions recorded in the registry.

3. Trial Design

The registry identifies this as a randomized phase II study with a parallel design. The two groups were checkpoint blockade immunotherapy plus stereotactic body radiation therapy and checkpoint blockade immunotherapy alone. Masking was listed as none. The registry names the University of California, San Diego as sponsor and records the study status as completed. It lists 106 participants as enrolled.

The primary outcome was objective response rate, recorded as a count of participants. Response was assessed at 16 weeks from baseline, using RECIST v1.0 criteria for target lesions assessed by MRI. The primary endpoint population is described as all participants who received at least one cycle of checkpoint blockade immunotherapy, with or without SBRT. This description does not establish whether every enrolled participant was included in the endpoint analysis, or how participants without an evaluable response were handled; those details are not reported in the registry record.

The registry also lists adverse events, progression-free survival, overall survival, and stable disease among the secondary outcomes. Stable disease has a posted result with an assessment timeframe of 5 years. The registry record does not include numerical results for progression-free survival or overall survival. Although the study is randomized, it was not masked, so participants and study personnel were not recorded as blinded to group assignment. The registry record does not report the original sample-size justification, the planned allocation ratio, the full statistical analysis plan, or whether interim analyses were planned or conducted.

4. Participant Flow and Accounting

The registry reports how participants moved through each stage of the study. All counts below are exactly as posted; missing counts are not inferred from other stages.

Overall Study

Analysis population for the primary outcome, as defined in the registry: All participants who received at least one cycle of checkpoint blockade immunotherapy with or without SBRT

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 Objective Response Rate, measured over Responses measured by RECIST at 16 weeks from baseline.

The primary endpoint is objective response rate, expressed in the registry as a count of participants. It records how many participants met the study’s response definition by the assessment at 16 weeks from baseline. Under RECIST v1.0, complete response means disappearance of all target lesions; partial response means a decrease of at least 30% in the sum of the longest diameters of target lesions. Overall response is the combination of complete and partial responses. The registry describes target-lesion assessment by MRI.

A binary response outcome makes a clinically interpretable comparison possible: each participant is classified according to whether the response definition was met. The resulting group proportions can be compared directly, while the counts show how many participants contributed to each group’s result. This type of endpoint is useful for evaluating whether treatment groups differ in the fraction meeting a prespecified response criterion at a defined assessment time.

The measure does not capture every aspect of a participant’s course. It does not, by itself, describe how long a response lasted, changes in symptoms, or outcomes after the assessment time. The registry separately lists progression-free survival and overall survival as secondary outcomes, but their numerical results are not reported in the registry record. A response result should therefore be interpreted as evidence about the stated RECIST-based endpoint, not as a substitute for those other outcomes.

7. Results Posted in the Registry

• Checkpoint Blockade Immunotherapy: 12.5% (6/48) versus 19.0% (11/58) on control; risk difference -6.5 percentage points (95% CI -20.2 to 7.3), risk ratio 0.66 (0.26–1.65); unadjusted two-proportion z-test p = 0.367.

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.

Rate of Stable Disease

• Endpoint type: Binary: the number of participants with the event, compared as proportions.
• Test: Unadjusted two-proportion z-test, with a Wald 95% confidence interval for the risk difference.
• Result:
  • Checkpoint Blockade Immunotherapy: 8.3% (4/48) versus 12.1% (7/58) on control; risk difference -3.7 percentage points (95% CI -15.2 to 7.7), risk ratio 0.69 (0.21–2.22); unadjusted two-proportion z-test p = 0.530.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between Checkpoint Blockade Immunotherapy and the control. The interval gives the range of effects that remain compatible with the data.

The registry lists adverse events, progression-free survival, overall survival, and stable disease as secondary outcomes. A numerical result is posted for stable disease, assessed at 5 years. Numerical progression-free survival and overall survival results are not reported in the registry record. The adverse-event information is reported separately as participant counts and selected serious-event terms. This means that the registry record does not supply a complete set of numerical secondary-endpoint comparisons from which to judge a consistent pattern across all listed outcomes.

The primary endpoint asks whether the groups differed in objective response at 16 weeks. Stable disease is a distinct disease-status category, while progression-free survival and overall survival concern time-to-event outcomes. They address related but not identical aspects of the study question, and they cannot be used interchangeably with objective response. The posted stable-disease result should therefore be considered alongside, but not as a substitute for, the primary endpoint. The available secondary information does not establish whether the response pattern is supported by longer-term outcomes.

Unadjusted secondary comparisons generally carry less evidential weight than a prespecified primary comparison because multiple outcomes and comparisons create more opportunities for chance findings. In general, multiplicity procedures can address that issue, but the registry record does not report whether adjustment was planned or applied. The record also does not report a complete secondary analysis plan. Consequently, secondary results should be treated as descriptive and interpreted cautiously, especially when not accompanied by a stated adjustment strategy or full outcome data.

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

• Number of Participants With Adverse Events
• Progression Free Survival
• Overall Survival
• Rate of Stable Disease

9. Statistical Interpretation

10. Statistical Methods Explained

Objective response is a binary outcome: a participant either meets the stated response definition or does not. For a binary outcome, the observed proportion is the count meeting the definition divided by the number assessed in the group. The registry reports counts and group sizes, along with proportions and comparative statistics. A difference in proportions is an absolute measure: it expresses how far apart the two group proportions are on the probability scale. The reported risk difference is -0.065 for CBI alone relative to CBI plus SBRT. Its sign depends on the order of the groups in the comparison, so it should be read with that reference direction in mind.

What does the confidence interval describe?

In general, a confidence interval describes the statistical uncertainty around an estimate under the assumptions of the method used to construct it. It is not a range containing a fixed percentage of individual participant outcomes, nor does it identify which value is true. For the risk difference, the interval runs from -0.202 to 0.073. Because it includes zero, the posted data are compatible with no difference as well as with differences on either side of zero. The interval’s width also indicates that the estimate is not highly precise.

How should the p-value be read?

In general, a p-value measures how unusual data at least as incompatible with a specified null hypothesis would be if that null hypothesis and the statistical model were correct. It does not give the probability that the null hypothesis is true, and it does not measure the clinical importance of a result. The reported unadjusted p-value for objective response is 0.367. It should be considered alongside the point estimate and confidence interval, rather than as a standalone verdict. The registry record does not report whether this p-value came from the sponsor’s prespecified primary analysis or detail the analysis procedure.

Why are relative measures also reported?

The risk ratio and odds ratio compare the groups on relative scales, rather than expressing an absolute difference. The registry reports a risk ratio of 0.659, with an interval from 0.263 to 1.651, and an odds ratio of 0.610, with an interval from 0.208 to 1.794. For a ratio, the null value is one; both reported intervals include that value. Relative scales can be useful for describing the relationship between group outcomes, but they can be less immediately intuitive than a difference in proportions. They are calculated from the same observed responses and should not be counted as independent confirmation.

What does randomization contribute?

In general, random assignment is intended to make the groups comparable, on average, with respect to factors known and unknown at the time of assignment. It supports an interpretation of the between-group comparison, but does not guarantee that every feature is balanced in a particular trial. The registry records random allocation and a parallel design; details of the allocation procedure, concealment, and analysis populations are not reported in the registry record. Masking was listed as none. Lack of masking can matter for aspects of study conduct and outcome assessment, although the registry’s RECIST-based endpoint is defined using target-lesion criteria.

The primary outcome is assessed at a fixed time, and the registry identifies the endpoint population as participants who received at least one cycle of CBI. The record does not explain how missing scans, deaths before assessment, withdrawals, or other unevaluable outcomes were treated. Those details matter because the analyzed group and outcome classification can affect the estimated response proportions.

The calculations and interpretive statements above concern the posted binary outcome. The registry record does not report a complete statistical analysis plan, the original sample-size rationale, planned interim analyses, or multiplicity procedures. Without those details, the reported estimates can be described, but the analysis cannot be fully reconstructed or checked against a prespecified plan.

11. Confidence Intervals and Precision

The primary comparison is based on 11 objective responses among 58 participants in the CBI-plus-SBRT group and 6 among 48 participants in the CBI-alone group. The estimated risk difference is -0.065 for CBI alone relative to CBI plus SBRT. Its 95% confidence interval extends from -0.202 to 0.073. This interval crosses zero, so the data do not pin down the direction of the difference with precision. Values consistent with the interval include a lower response proportion in the CBI-alone group, no difference, and a higher proportion in that group.

Precision is limited by the amount of information in the comparison: the response counts are small relative to the group sizes, and the confidence interval spans a broad range of possible differences. The point estimate is not a guarantee that the underlying difference is close to -0.065. A confidence interval is a measure of uncertainty about the estimated group contrast under the method’s assumptions; it is not a prediction interval for individual participants and does not remove uncertainty about study conduct or missing outcome data.

The relative measures show a similar uncertainty pattern. The risk ratio interval, 0.263 to 1.651, includes one, as does the odds ratio interval, 0.208 to 1.794. These intervals reflect the same response data on different scales. The registry record does not describe the procedure used to construct the intervals or report an adjusted estimate. The appropriate reading is therefore that the observed groups differed by the stated estimate, while the range of plausible values remains wide and includes the null comparison.

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 figures are illustrations based on the observed effect, not a report of the trial’s original design calculation. The registry record does not report the original sample-size justification or design assumptions. The illustration assumes a two-sided significance level of 0.05, equal allocation between the two arms, and a normal approximation. It varies the effect to be detected by using the stated fractions of the observed effect.

For this binary outcome, the planning figures are participants per arm, not total events. The 80% power column gives the illustrative number of participants per arm for a design with an 80% chance of detecting the specified effect under the stated assumptions. The 90% power column gives the corresponding per-arm number for a 90% chance. These are design-planning concepts: power is the probability of detecting an effect of a specified size under a set of assumptions if that effect is present. It is not the probability that a finding is true.

The display considers planning for 100% of the observed effect, 75% of the observed effect, and 50% of the observed effect. Smaller effects require more participants to detect under otherwise unchanged assumptions, which is why the illustrative sample sizes grow as the target effect becomes smaller. The estimates are sensitive to the assumed effect and to the planning method. Because the observed effect is estimated from the same trial data and is uncertain, using it as a planning target should not be mistaken for a reliable forecast of the effect in a future study.

These figures are not observed power. They do not describe the probability that this completed trial detected a true effect, and they do not replace interpretation of the observed estimate and confidence interval.

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

n is the number of participants in each arm, p₀ and p₁ are the control and treatment proportions, and p̄ is their average.

Worked calculation for this trial

1. Control proportion p₀ = 0.190; treatment proportion p₁ = 0.125; average p̄ = 0.157.
2. First term: z_1−α/2 × √[2p̄(1−p̄)] = 1.96 × 0.5149 = 1.0092.
3. Second term: z_1−β × √[p₀(1−p₀) + p₁(1−p₁)] = 0.842 × 0.5129 = 0.4317.
4. n = (1.0092 + 0.4317)² / (-0.0647)² = 496.7, rounded up to 497 participants per arm 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
p0 <- 0.189655172413793                          # control proportion
p1 <- 0.125                          # treatment proportion
n_per_arm <- function(power, frac = 1) {
  q1 <- p0 + (p1 - p0) * frac               # smaller effect = fraction of the observed difference
  pbar <- (p0 + q1) / 2
  z_b <- qnorm(power)
  ceiling(round((z_a * sqrt(2 * pbar * (1 - pbar)) + z_b * sqrt(p0 * (1 - p0) + q1 * (1 - q1)))^2 / (q1 - p0)^2, 6))
}
for (f in c(1, 0.75, 0.5))
  cat(sprintf("%3.0f%% of observed effect: n per arm = %s (80%% power), %s (90%% power)\n", 100 * f,
              format(n_per_arm(0.80, f), big.mark = ","), format(n_per_arm(0.90, f), big.mark = ",")))

# Check against R's built-in function (unrounded n per arm)
cat("power.prop.test:", round(power.prop.test(p1 = p0, p2 = p1, power = 0.80)$n, 1), "\n")

# Simulation: how often does the z-test reject at the 80%-power sample size?
set.seed(2843165)
n    <- n_per_arm(0.80)
reps <- 20000
x0 <- rbinom(reps, n, p0); x1 <- rbinom(reps, n, p1)
ph <- (x0 + x1) / (2 * n)
z  <- ((x1 - x0) / n) / sqrt(ph * (1 - ph) * 2 / n)
cat(sprintf("Simulated power at n = %s per arm: %.3f (%d replicates)\n", format(n, big.mark = ","), mean(abs(z) > z_a, na.rm = TRUE), reps))

Output from running the code

100% of observed effect: n per arm = 497 (80% power), 665 (90% power)
 75% of observed effect: n per arm = 921 (80% power), 1,232 (90% power)
 50% of observed effect: n per arm = 2,153 (80% power), 2,882 (90% power)
power.prop.test: 496.7 
Simulated power at n = 497 per arm: 0.807 (20000 replicates)

The simulation draws many pairs of event counts at the planned sample size and counts how often the two-proportion z-test rejects the null. It should land close to the target power; at very small required sample sizes it can fall below it, because the normal approximation is rough there.

14. Multiplicity, Missing Data and Analysis Populations

The registry identifies objective response rate as the primary outcome and lists several secondary outcomes. The record does not report a multiplicity strategy, such as a procedure for controlling the chance of false-positive findings across several outcomes or comparisons. It also does not report whether particular secondary analyses were designated as confirmatory or exploratory in the original analysis plan. Without this information, the statistical weight of individual secondary findings cannot be fully assessed. Unadjusted secondary comparisons should be read cautiously because multiple looks at outcomes can increase the chance of apparently notable findings arising by chance.

The record describes the primary endpoint population as all participants who received at least one cycle of checkpoint blockade immunotherapy, with or without SBRT. It does not state whether this population is identical to all randomized participants or explain how participants who did not receive a cycle were handled. The registry record does not report the number of missing or unevaluable response assessments, the reasons for missingness, or how such cases were classified in the analysis. It also does not describe approaches to missing data for the listed secondary outcomes.

The registry does not report a complete statistical analysis plan, details of an intention-to-treat analysis, or planned interim analyses. These omissions do not establish that no such procedures existed; they mean the procedures are not reported in the registry record. The primary result can be described from the posted numbers, but its correspondence to the original prespecified analysis and the handling of incomplete outcome information cannot be verified from the registry record alone.

15. 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: abdominal pain (10.4%), vomiting (10.4%), thromboembolic event (8.6%), nausea (6.2%), cough (6.2%).

The registry reports serious adverse events for 24 of 58 participants in the CBI-plus-SBRT group and 15 of 48 participants in the CBI-alone group. Other adverse events are reported for 44 of 58 and 35 of 48 participants, respectively. These are participant counts in the registry’s adverse-event groups, not estimates of whether an event was caused by one treatment or the other. The record also lists 36 deaths in the CBI-plus-SBRT group and 29 in the CBI-alone group. The timeframe and attribution rules for these death counts are not reported in the registry record.

The listed serious-event terms include abdominal pain and vomiting, each reported as 10.4%; thromboembolic event at 8.6%; and nausea, cough, and dyspnea, each at 6.2%. The registry record does not provide enough context to infer the timing, duration, severity distribution beyond the serious-event designation, or causal relationship of these events to study treatment. These figures describe recorded events; they do not establish comparative safety or determine the cause of any individual event.

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

The posted primary result estimates the difference in objective response between two randomized groups at 16 weeks from baseline. The observed response counts were 11 of 58 participants with CBI plus SBRT and 6 of 48 with CBI alone. The estimated risk difference, expressed for CBI alone relative to CBI plus SBRT, is -0.065, with a 95% confidence interval from -0.202 to 0.073. The interval includes zero, and the unadjusted p-value is 0.367. The estimate is therefore uncertain, and the data do not establish a clear difference in objective response between the groups.

This result does not show that the groups are identical. An interval crossing zero means that the observed data do not distinguish the null comparison from a range of possible group differences with sufficient precision under the reported analysis. Nor does the point estimate alone establish the size or direction of a reproducible effect. The observed difference is based on the participants and outcome information recorded in this trial.

The endpoint is a RECIST-defined response assessment, not a direct measure of every outcome relevant to advanced metastatic cancer. The registry lists progression-free survival and overall survival as secondary outcomes, but their numerical results are not reported in the registry record. The primary response comparison should not be interpreted as a result about survival, long-term disease control, quality of life, or the full balance of benefits and harms.

The study was randomized and parallel-group, which supports a between-group comparison, but it was not masked. Important analysis details—including missing outcome handling, the original statistical plan, and multiplicity procedures—are not reported in the registry record. The registry’s results are therefore useful as a description of the posted comparison, but they do not answer every question about study conduct, outcome completeness, or the interpretation intended by the original analysis plan.

No treatment recommendation follows from these statistics. They describe how the recorded endpoint differed between the trial groups and how uncertain that estimated contrast is; they do not determine what an individual should receive.

17. Why This Trial Matters Statistically

This trial illustrates how a randomized phase II comparison can be statistically informative even when it does not yield a precise estimate. The endpoint is a straightforward binary outcome, and the registry provides both group counts and a comparative estimate. Reading the count, effect estimate, confidence interval, and p-value together makes clear that the observed direction is not the same as a precise or conclusive estimate of a group difference.

It also demonstrates why the scale of an effect matters. A risk difference expresses an absolute contrast, while risk ratios and odds ratios express relative contrasts. These measures can help describe the same data from different perspectives, but they do not provide independent evidence. Their intervals all include the relevant null value, reinforcing the importance of uncertainty rather than a single point estimate.

The registry record also highlights the distinction between a posted result and a fully documented statistical analysis. The original sample-size justification, missing-data procedures, multiplicity approach, and full analysis plan are not reported in the registry record. Such information matters for assessing what the trial was designed to detect, how incomplete outcomes were handled, and how secondary findings should be interpreted. The planning illustrations based on the observed effect are not a substitute for the original design rationale.

Finally, the separation between objective response and secondary outcomes is important. A response assessment at 16 weeks does not stand in for survival outcomes, and the listed survival results are not reported in the registry record. Statistical interpretation depends on matching conclusions to the outcome actually measured, while treating imprecision and incomplete reporting as part of the evidential picture.

18. 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 registry record does not report the original sample-size justification, so it is not possible to determine from the record whether the trial was designed around a particular clinically meaningful response difference. The planning illustrations based on the observed effect do not recover that original rationale. The primary comparison also has limited precision: the objective-response counts are 11 and 6, and the confidence interval for the risk difference ranges from -0.202 to 0.073.

The primary endpoint is defined for participants who received at least one cycle of checkpoint blockade immunotherapy. The record does not explain how this group relates to all randomized participants, or how missing, unevaluable, or absent 16-week assessments were handled. The endpoint assessment used MRI and RECIST v1.0 criteria, but details about assessment procedures, review, or safeguards against assessment bias are not reported in the registry record. Masking was listed as none.

The registry does not report the full statistical analysis plan, multiplicity procedures, or whether interim analyses were conducted. It also does not provide numerical progression-free survival or overall survival results despite listing those as secondary outcomes. These gaps restrict assessment of the full endpoint pattern and the relationship between the posted analysis and the original plan.

The adverse-event information includes counts and selected serious-event terms, but the record does not report enough detail to interpret event timing, attribution, or the basis for the death counts. These limitations do not negate the posted numbers; they define what can and cannot be concluded from the registry record alone.

19. Related Tutorials

20. Related Statistical Calculators

21. Sources

• ClinicalTrials.gov: Checkpoint Blockade Immunotherapy Combined With Stereotactic Body Radiation in Advanced Metastatic Disease — NCT02843165.
• Registry record last updated 2025-09-30; status last verified 2025-09.
• Results first posted 2025-07-28.
• 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.

22. Record Summary

The registry records NCT02843165 as a completed randomized phase II, parallel-group study of checkpoint blockade immunotherapy plus stereotactic body radiation therapy versus checkpoint blockade immunotherapy alone in advanced metastatic cancer. Masking was listed as none, and enrollment was 106. The primary endpoint was RECIST v1.0 objective response at 16 weeks from baseline among participants who received at least one cycle of immunotherapy.

Objective response was recorded for 11 of 58 participants in the CBI-plus-SBRT group and 6 of 48 in the CBI-alone group. The estimated risk difference for CBI alone relative to the combination group was -0.065, with a 95% confidence interval from -0.202 to 0.073 and an unadjusted p-value of 0.367. The interval includes zero and indicates substantial uncertainty about the contrast.

The registry lists adverse events, progression-free survival, overall survival, and stable disease as secondary outcomes. Stable disease results are posted, but numerical progression-free survival and overall survival results are not reported in the registry record. The original design assumptions, full analysis plan, missing-data handling, and multiplicity procedures are also not reported.