Neodjuvant Nivolumab and Lirilumab, Followed by Surgery, Followed by Adjuvant Nivolumab and Lirilumab, in SCCHN: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Neodjuvant Nivolumab and Lirilumab, Followed by Surgery, Followed by Adjuvant Nivolumab and Lirilumab, in SCCHN (NCT03341936), a na phase 2 study. The primary outcome is 1-Year Disease-Free Survival Percentage.

2. Clinical Question

This is a question about outcomes observed after a treatment sequence in a selected clinical population. It is not a randomized comparison of the combination against another treatment or against no treatment. Accordingly, the study can describe the recorded outcome in its participants, but the design does not by itself establish how outcomes would have differed under an alternative approach.

The registry lists 1-Year Disease-Free Survival Percentage as the primary outcome. Its description counts participants who were alive and disease free at one year past salvage surgery, while participants alive at their last contact before that mark are censored. The timeframe is one year since salvage surgery, up to 1 year and 23 days since treatment start. A numerical primary outcome result is not reported in the registry record, so the clinical question cannot be answered from the recorded result information.

3. Trial Design

The registry describes a phase 2, single-group study sponsored by Dana-Farber Cancer Institute. The study concerns nivolumab and lirilumab for locoregionally recurrent squamous cell carcinoma of the head and neck; the official title specifies patients with relapsed, resectable disease. The listed enrollment is 29. The record gives a start date of 2018-03-15, a primary completion date of 2021-07-06, and a status of active, not recruiting.

The treatment sequence is described as nivolumab and lirilumab before salvage surgical resection, followed by adjuvant nivolumab and lirilumab. Both interventions are listed as drugs, and the arm description says they are administered intravenously. It describes a single dose of each drug before surgery and gives some cycle-level details for subsequent treatment. However, that description ends partway through a sentence, so the full adjuvant schedule is not reported in the registry record.

There is no allocated control arm: allocation is listed as not applicable, masking as none, and the model as single group. This design is suited to describing outcomes and safety observations in the treated group. It does not provide a randomized, concurrent treatment contrast. Any comparison with outcomes from other populations or studies would need to account for differences in patient selection, care, and follow-up; such a comparison is not specified in the registry record.

The primary endpoint is a time-to-event outcome estimated by Kaplan-Meier methods. Secondary outcomes listed include response at salvage surgery, median disease-free survival, one-year overall survival percentage, and median change in programmed cell death ligand-1 combined positive score. The registry identifies five outcome measures, but the analysis information and numerical results are not reported in the registry record.

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

Reasons for not completing this period:

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 1-Year Disease-Free Survival Percentage, measured over 1 year since salvage surgery, up to 1 year and 23 days since treatment start.

The primary endpoint is the percentage of participants alive and disease free one year after salvage surgery. The registry states that Kaplan-Meier methods are used and that participants alive at their last contact before the one-year mark are censored. The timeframe is one year since salvage surgery, up to 1 year and 23 days since treatment start.

This endpoint combines two aspects of outcome: being alive and having no recorded disease at the specified time. It is therefore different from an endpoint that counts only tumor response at surgery or only overall survival. It is also a time-to-event measure: participants may have different lengths of follow-up, and censoring allows information from participants whose status is known only up to an earlier contact to contribute to the estimate.

In general, a one-year estimate can be clinically interpretable because it refers to a defined follow-up point after an operation. Its precision depends on the available follow-up and the number and timing of events; those details are not reported in the registry record. The endpoint description identifies a 95% confidence interval as the dispersion measure, but no numerical estimate or interval is reported. Without those results, the proportion estimated to be alive and disease free at one year, and the uncertainty around that estimate, cannot be assessed from this record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

How does the single-group design shape interpretation?

The study is listed as single group, with allocation not applicable and no masking. Participants therefore do not form randomized treatment and control groups within this trial. In general, random allocation helps balance known and unknown prognostic factors across groups, on average. Without that design feature, an outcome observed after treatment cannot be separated from the outcome that might have occurred under another treatment or under usual care. This is a limitation on causal interpretation, not a reason to disregard descriptive observations.

The treatment sequence also includes salvage surgery. The primary endpoint is measured after that surgery, so it describes the outcome of the overall treatment context recorded by the study, rather than an isolated drug effect. The registry does not report a design that separates the contributions of nivolumab, lirilumab, surgery, or other care.

What does Kaplan-Meier estimation do?

The registry explicitly states that disease-free survival is analyzed using Kaplan-Meier methods. In general, this method estimates the probability of remaining free of the event over time while allowing participants to have different follow-up durations. A participant whose event status is not observed through the full follow-up period can contribute information up to the last known contact and then be censored. Censoring is not itself counted as an event.

The endpoint description says that participants alive at last contact before the one-year mark are censored. It does not provide details about the event definition beyond the endpoint wording, the number of censored participants, event timing, or follow-up completeness. Those details are important for understanding how much information supports the estimate and whether the assumptions underlying the method are plausible. They are not reported in the registry record.

How should the confidence interval be understood?

The primary endpoint lists a 95% confidence interval. In general, a confidence interval communicates statistical uncertainty around an estimate: a narrower interval indicates greater precision under the method and assumptions used, while a wider interval indicates less precision. It does not describe the range of outcomes for individual participants, and it does not account automatically for every source of bias. The registry record names the interval type but reports neither the endpoint estimate nor interval limits, so its precision cannot be evaluated.

What can be inferred from the outcome listings?

The registry names response at salvage surgery, median disease-free survival, one-year overall survival percentage, and median change in programmed cell death ligand-1 combined positive score as secondary outcomes. It identifies five outcome measures in total. The registry record does not report numerical outcome results, detailed analysis methods for those secondary outcomes, or a statistical analysis plan. It is therefore not possible to assess the estimators, uncertainty measures, or analytic populations for those outcomes from the record.

In general, different outcome types call for different statistical summaries. A binary outcome may be expressed as a proportion, a time-to-event outcome may account for censoring, and a continuous measurement may be summarized by a change or distribution. These general distinctions do not establish which detailed methods were used for each listed secondary outcome; those methods are not reported in the registry record.

What does the sample-size planning information mean?

The sample-size assumptions describe planning illustrations based on an observed effect, with a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. They specify that the effect to detect is a stated fraction of the observed effect. For time-to-event outcomes, the illustration is described in terms of a total number of events; for other outcomes, it is described as participants per arm. These are planning illustrations, not observed power and not evidence that the trial was designed using those assumptions. The registry does not report the numerical illustrations or the trial's own sample-size justification.

In general, a planning calculation explores how much information a future study might need under stated assumptions. If it is based on an observed effect, it inherits uncertainty in that estimate and should not be read as a guarantee that a study will achieve a particular result. The record does not report the observed primary effect needed to evaluate such an illustration. It also describes a single-group trial, whereas the stated planning assumptions use equal allocation between two arms; the relation between those assumptions and the trial design is not reported in the registry record.

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("Nivolumab+Lirilumab")
n      <- c(28)
events <- c(15)
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  Nivolumab+Lirilumab  28  15  53.6  33.9  72.5  35.8  70.5  35.7  70.6

11. Multiplicity, Missing Data and Analysis Populations

The registry identifies five outcome measures and lists four secondary outcomes in addition to the primary endpoint. It does not report whether the trial prespecified a hierarchy among outcomes, adjusted for multiple statistical tests, or treated secondary analyses as exploratory. When several outcomes are examined, the chance of at least one apparently unusual result can increase; in general, multiplicity procedures are used to manage that issue. Without a reported plan or results, it is not possible to determine how multiplicity was handled or how it should affect interpretation.

The primary endpoint description specifies Kaplan-Meier analysis and a 95% confidence interval. The registry record does not report an analysis plan, details of the analysis population, the event definition beyond the endpoint wording, or how participants with missing follow-up information were handled. It states that participants alive at last contact before the one-year point are censored, but does not provide the number censored, reasons for loss of follow-up, or further assumptions about censoring.

In general, missing outcome information can affect both the estimate and its precision, particularly if availability of follow-up is related to participants’ outcomes. Censoring methods address incomplete observation under assumptions; they do not make missing information irrelevant. Because the record does not provide outcome data or follow-up details, the direction or extent of any effect from missing information cannot be assessed.

The registry's sample-size planning assumptions are described as illustrations, not as the trial's own design justification. The actual sample-size justification and any interim analyses are not reported in the registry record. No numerical primary endpoint result or analysis population is available for assessment.

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: dyspnea (14.3%), dysphagia (10.7%), wound infection (7.1%), productive cough (7.1%), cardiac arrest (3.6%).

For the nivolumab-plus-lirilumab group, the registry reports 28 participants at risk for serious adverse events and 12 affected. For other adverse events, it reports 28 at risk and 28 affected. The record also lists 7 deaths. It does not state in this safety entry whether those deaths were caused by treatment or disease, and they should not be interpreted as treatment-related on the basis of the count alone.

The most frequently listed serious-event terms are dyspnea (14.3%), dysphagia (10.7%), wound infection (7.1%), and productive cough (7.1%). Cardiac arrest and chest pain - cardiac are each listed at 3.6%. These percentages describe the registry's reported event terms; the record does not give additional detail about event severity grading, timing, recurrence, or attribution.

In general, a participant-level count of people affected is different from a count of individual event episodes, since one person may experience more than one event. The registry entry does not clarify the counting convention for the listed terms. These figures describe recorded safety observations in a single group; without a comparator, they cannot establish whether the treatment caused an event or how the event frequency compares with another treatment.

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

The registry record establishes the study question and design: a phase 2 single-group evaluation of nivolumab and lirilumab in relapsed, resectable squamous cell carcinoma of the head and neck, with treatment given around salvage surgery. It defines one-year disease-free survival after surgery as the primary endpoint and specifies Kaplan-Meier methods. It also reports safety counts and serious adverse-event terms for the treatment group.

What it does not establish from the recorded results is the numerical one-year disease-free survival estimate, its confidence interval, or the results of the listed secondary outcomes. Those results are not reported in the registry record. Consequently, the available information does not quantify the primary outcome or its precision and cannot answer how often participants were alive and disease free at the stated time.

Even if an outcome estimate were available, a single-group design would not establish a treatment effect relative to another approach. In general, an observed outcome in a treated group is not the same as a comparative effect: the latter requires a credible estimate of what would have happened to a comparable population under an alternative. The study record lists no concurrent comparator.

The safety figures are likewise descriptive. They identify recorded participants affected and selected serious-event terms, but the record does not provide causal attribution or a comparison group. The count of deaths is not, by itself, an explanation of their causes.

Overall, the information supports understanding what treatment sequence was studied, which primary outcome was intended, and what safety entries are recorded. It does not support a claim that the treatment works or does not work, nor does it establish how its outcomes compare with another treatment. The missing numerical outcome results and the lack of a comparator are central limits on what can be concluded.

14. Why This Trial Matters Statistically

This trial raises a clear statistical question: how to describe a time-to-event outcome after a treatment sequence that includes salvage surgery, when follow-up may differ among participants. Kaplan-Meier estimation is identified for the primary disease-free survival endpoint, and the registry explains that participants alive at their last contact before the one-year mark are censored. This makes the endpoint definition and handling of incomplete follow-up important to interpretation.

The design also illustrates the distinction between describing an outcome and estimating a treatment effect. A single-group study can record what occurred among participants receiving the combination and undergoing the described care. Without a comparator, it cannot isolate the contribution of the drugs or establish how outcomes would have differed under another approach. That distinction matters when interpreting disease-free survival and safety observations.

The registry record also highlights why precision is not conveyed by naming a confidence interval alone. A 95% confidence interval is specified, but neither its bounds nor the underlying endpoint estimate are reported. Without them, readers cannot judge the uncertainty associated with the primary outcome. Follow-up and censoring details would further help clarify how much information contributes to the estimate.

Finally, the outcome list and planning assumptions raise questions about analysis choices that cannot be resolved from the record. The statistical analysis plan, multiplicity handling, sample-size justification, and numerical sample-size illustrations are not reported. These gaps do not change the stated design, but they limit evaluation of how the planned analyses were connected to the trial question.

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 limitation for statistical interpretation is that the registry record does not report the numerical primary outcome result or its 95% confidence interval. Although the endpoint and its intended Kaplan-Meier method are described, the estimate's size and precision cannot be assessed. Numerical results for the listed secondary outcomes are also not reported.

The single-group design provides no randomized comparator. As a result, the record cannot distinguish outcomes associated with the treatment sequence from outcomes related to participant characteristics, disease course, surgery, or other care. The registry does not report an adjusted comparative analysis.

The endpoint depends on time-to-event follow-up and censoring, but the number of events and censored participants, follow-up completeness, and detailed event definition are not reported. The description says participants alive at last contact before the one-year mark are censored; it does not provide further information needed to evaluate missing follow-up or censoring assumptions.

The treatment schedule description is incomplete: the cycle details end partway through a sentence. The record therefore does not fully specify the adjuvant schedule. It also does not report the statistical analysis plan, analysis populations, multiplicity approach, interim analyses, or the trial's sample-size justification. Planning assumptions are described, but numerical illustrations are not reported. These limitations restrict assessment of both the planned analyses and the results available for interpretation.

For safety, the record reports counts and selected serious-event percentages but does not provide attribution, timing, grading details, or a comparator. The relationship between the enrollment entry and the safety risk counts is not explained. These omissions mean the safety entries should be read as descriptive registry information rather than comparative evidence.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Neodjuvant Nivolumab and Lirilumab, Followed by Surgery, Followed by Adjuvant Nivolumab and Lirilumab, in SCCHN — NCT03341936.
• Registry record last updated 2025-06-18; status last verified 2025-06.
• Results first posted 2022-06-16.
• 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 registry record describes a phase 2, single-group study sponsored by Dana-Farber Cancer Institute, evaluating nivolumab and lirilumab around salvage surgery for relapsed, resectable squamous cell carcinoma of the head and neck. Listed enrollment is 29. The record gives a start date of 2018-03-15, a primary completion date of 2021-07-06, and status active, not recruiting.

The primary endpoint is one-year disease-free survival after salvage surgery, estimated using Kaplan-Meier methods with a 95% confidence interval. The numerical result and interval are not reported in the registry record. The safety entry lists 28 participants at risk for serious adverse events, 12 affected by serious adverse events, 28 affected by other adverse events, and 7 deaths. No randomized comparator is listed.