PRISM (Panitumumab Regimen In Second-line Monotherapy of Head and Neck Cancer): Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for PRISM (Panitumumab Regimen In Second-line Monotherapy of Head and Neck Cancer) (NCT00446446), a na phase 2 study. The primary outcome is Objective Response Rate.

2. Clinical Question

The central statistical question is descriptive: what proportion of the defined study population had an objective response during the assessment period, and how precisely was that proportion estimated? A response rate can describe tumor responses observed under the study’s assessment rules. In a single-arm study, it cannot by itself establish how outcomes would have differed under another treatment or under no study treatment.

The registry record identifies an objective response rate endpoint but does not report its observed value, the number of participants with a response, or the stated 95% confidence interval. It therefore does not allow the response proportion or its precision to be described. The record also does not report a comparative estimate. The study’s stated aim was to estimate the effect of second-line panitumumab monotherapy on objective response in this patient population; the available record details the question and endpoint definition, but not the primary endpoint result.

The endpoint was assessed from investigator review of scans using modified RECIST version 1.0. Responses had to meet the specified tumor criteria and be confirmed at least 28 days after response criteria were first met. These requirements define what counted as a response; they do not substitute for reporting how many participants met that definition.

3. Trial Design

PRISM was a phase 2, open-label, multicenter, single-group trial of second-line panitumumab monotherapy in patients with metastatic or recurrent squamous cell carcinoma of the head and neck. The registry record lists enrollment of 52 and identifies Amgen as the sponsor. The recorded status is completed. The study start date was 2007-10-30, and the primary completion date was 2010-12-15.

All participants were assigned to the panitumumab group; there was no allocation to a control arm. The study was unmasked, so it was open-label. Panitumumab was given by intravenous infusion at 9 mg/kg every 21 days. The stated stopping conditions were disease progression, unacceptable toxicity, withdrawal of consent, death, or end of study. The primary endpoint assessment period ran from the first dose through the data cut-off date of 16 December 2010. Median treatment duration was 9.0 weeks, with a range of 3.0 to 68.9 weeks.

The primary endpoint population is described as the full analysis set: all enrolled participants who received at least one dose and had measurable disease at baseline. The registry record does not state how many participants met that definition. Although enrollment is recorded as 52, that entry alone does not establish the number included in the endpoint analysis.

The design supports a description of response and safety observed among participants treated in the study. Without a randomized or other concurrent comparator, differences from an external benchmark would not be controlled by the trial design. The registry record does not report a planned comparator, a control group, a statistical analysis plan, or a sample-size justification. The listed sample-size assumptions concern planning illustrations, not a reported design rationale for this trial. No outcome analysis records are listed 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.

Before assignment: Results are reported for the primary analysis with a data cut-off date of 16 December 2010.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: Full analysis set (all enrolled participants who received at least 1 dose of panitumumab) with measurable disease at Baseline

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 From first dose of study drug until the data cut-off date of 16 December 2010. Median duration of treatment was 9.0 weeks (range: 3.0 to 68.9 weeks)..

The primary endpoint was objective response rate, defined as the percentage of participants whose best tumor response was complete response or partial response before initiation of subsequent anti-cancer therapy. Response assessments were based on investigators’ review of scans using modified Response Evaluation Criteria in Solid Tumors (RECIST) version 1.0. The registry record specifies a 95% confidence interval as the measure of dispersion for this endpoint.

A complete response required disappearance of all target lesions and non-target lesions, with no new lesions. A partial response required at least a 30% decrease in target-lesion size, without progression of existing non-target lesions or new lesions. The definition also allowed partial response when all target lesions disappeared but one or more non-target lesions remained, provided the findings did not qualify as complete response or progressive disease and there were no new lesions. A response had to be confirmed at least 28 days after the criteria were first met.

Objective response is used as a binary endpoint: each participant either meets the response definition or does not. The resulting proportion gives a compact description of tumor response under the study’s assessment rules. In general, a confidence interval communicates the uncertainty around an estimated proportion; it reflects that the observed study participants are not the only possible group of patients who might have been enrolled. It does not resolve limitations arising from the single-arm design or establish a treatment comparison.

The record defines the endpoint but does not report the observed response proportion, response count, or confidence interval. The endpoint’s numerical result and its precision are therefore not reported in the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The methods described in the registry record establish what the study intended to measure and how response was classified. They do not include a complete account of the statistical analysis. In particular, no outcome analyses are listed, and the record does not report the primary response estimate, its confidence interval, or the analysis procedures used to produce them.

What does a response proportion represent?

Objective response rate is a binary-outcome summary. A participant contributes to the response category if the best response meets the specified complete-response or partial-response definition; otherwise, the participant does not meet the primary endpoint. The proportion is meaningful only in relation to its analysis population and denominator. Here, the endpoint population is described as enrolled participants who received at least one dose and had measurable disease at baseline. The number in that population is not reported in the registry record, so the denominator used for the primary endpoint cannot be confirmed.

In general, binary outcomes are often summarized by the number meeting the endpoint and the number assessed, alongside a percentage. Those quantities are not reported for this endpoint in the registry record. The enrollment entry of 52 is not enough to reconstruct them: enrollment and the defined primary analysis population are not necessarily interchangeable, and no endpoint count is stated.

How should the confidence interval be understood?

The registry record specifies a 95% confidence interval for the objective response rate, but does not report its limits or the method used to calculate it. In general, a confidence interval expresses uncertainty in an estimated quantity under the assumptions of the calculation method. A narrower interval indicates greater precision in that estimate, while a wider interval indicates less precision. A confidence interval is not a guarantee that the true value lies within a particular range, nor does it address bias caused by study selection, assessment, or design.

For a single-group response proportion, the interval concerns the estimated proportion in the population represented by the study, under the analysis assumptions. It does not create a comparison group. A confidence interval around a single-arm response estimate cannot by itself show the size of a difference from another treatment, because no concurrent comparator estimate is reported. Since neither the point estimate nor interval is reported, the precision of the response estimate cannot be assessed.

What does the response definition add?

The endpoint uses investigator review of scans and modified RECIST version 1.0. The registry record describes lesion-based criteria for complete and partial response and requires confirmation at least 28 days after response criteria are first met. It also restricts the endpoint to responses before subsequent anti-cancer therapy begins. These rules make the endpoint operational: they specify which observations count as responses and when an observation qualifies.

In general, prespecified response rules can improve consistency by giving assessors a shared classification framework. They do not eliminate all measurement uncertainty. This record identifies investigator review and an open-label design, but does not report independent central review, adjudication procedures, or blinding of scan assessors. Those procedures are not reported in the registry record.

What can be inferred from a single-group design?

A single-group design estimates outcomes observed in participants who received the study treatment. In general, it can describe response frequency, treatment exposure, and safety events within the enrolled group. It cannot use randomization to balance measured and unmeasured prognostic factors against a concurrent control group. Without a control arm, observed outcomes cannot be interpreted as a direct randomized estimate of what treatment changed.

Open-label status means the study is identified as unmasked. The registry record does not report whether this affected the conduct or assessment of the endpoint. It is appropriate to note the design when considering how responses were assessed, without assuming that any particular bias occurred.

What do the planning assumptions mean?

The registry record describes sample-size illustrations based on the observed effect, with a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. It states that the effect to detect is a stated fraction of the observed effect. These are planning assumptions for illustrations, not the trial’s own sample-size justification and not an observed-power analysis.

The trial itself is single-arm, while the illustrations refer to equal allocation between two arms. That planning setup does not mean the trial had a comparator group. The record does not report the numerical planning outputs, nor does it state the trial’s sample-size justification. In general, a planning calculation describes a hypothetical design under specified assumptions; it does not describe the probability that a completed study has demonstrated an effect. A sample-size illustration is not a substitute for the observed endpoint estimate and its uncertainty.

More broadly, the registry record does not report the method used for the primary endpoint confidence interval, handling of missing response assessments, an interim-analysis plan, or a complete statistical analysis plan. These omissions limit the methodological detail available for interpreting the endpoint. They do not justify filling in a method by assumption.

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("Panitumumab")
n      <- c(51)
events <- c(2)
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  Panitumumab  51  2  3.9  0.5  13.5  1.1  13.2  1.2  13.2

11. Multiplicity, Missing Data and Analysis Populations

The registry record lists objective response rate as the primary outcome and lists several secondary outcomes: time to response, duration of response, rate of disease control, time to progression, progression-free survival, overall survival, and participants with adverse events. It records 8 outcome measures and no analysis records. The listed secondary outcomes therefore indicate additional intended measures, but their numerical results are not reported in the registry record.

Multiplicity arises when several outcomes or analyses are considered. In general, the more statistical questions examined, the more important it is to understand which were primary, which were secondary, and whether methods were planned to account for multiple testing. The registry record does not report a multiplicity adjustment, a testing hierarchy, or a complete statistical analysis plan. It is therefore not possible to determine how the listed outcomes were prioritized statistically or whether any adjustment was planned.

The endpoint population is defined as enrolled participants who received at least one dose and had measurable disease at baseline. The record does not report the number included in that population or the number with evaluable response assessments. It also does not describe how missing or unevaluable scans, withdrawals, or participants who began subsequent therapy before response confirmation were handled in the analysis. Those missing-data and analysis-population details are not reported in the registry record.

In general, missing outcome information can affect both the analysis denominator and the interpretation of a proportion. Different rules for excluding or classifying participants with missing assessments can yield different estimates. No such rule should be inferred from the endpoint definition alone. The record’s population description and response criteria are informative, but they do not establish how incomplete observations were treated.

12. Safety Results

The registry reports serious adverse events as affected participants divided by participants at risk.

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: dysphagia (3.8%), vomiting (3.8%), pneumonia (3.8%), lymphopenia (1.9%), cardiac failure congestive (1.9%).

For the panitumumab group, the registry record lists 52 participants at risk for serious adverse events and 14 affected. It separately lists 52 at risk and 50 affected for other adverse events. These are two different safety summaries; the record does not state whether the participants affected in one category overlap with those in the other. No death count is reported in the registry record.

The listed serious adverse-event terms are dysphagia, vomiting, and pneumonia, each at 3.8%; lymphopenia, cardiac failure congestive, and myocardial infarction, each at 1.9%. These percentages are quoted as recorded. The record does not give event counts for each term, so the percentages should not be converted into counts or treated as a complete description of all events.

In general, a count of participants affected is different from a count of events: one participant may experience more than one event. The registry entry does not provide enough detail to determine event recurrence, timing, severity grades beyond the serious-event classification, or relationships between events. These safety data describe reports within a single treatment group. With no control group, they do not provide a comparative estimate of excess risk or establish whether an event was caused by treatment.

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

The registry record establishes that PRISM was a phase 2, open-label, single-arm study of panitumumab monotherapy for patients with metastatic or recurrent squamous cell carcinoma of the head and neck. It also defines the primary objective-response endpoint, its assessment rules, and the population intended for that analysis. Those details clarify what the trial set out to measure.

The record does not report the primary endpoint result. There is no reported objective response proportion, response count, or 95% confidence interval. As a result, the magnitude and precision of the primary endpoint cannot be evaluated from the registry record. A treatment schedule, endpoint definition, and study enrollment entry are not substitutes for an outcome estimate.

Even if a response proportion were reported, a single-arm study would describe observed responses in the treated group rather than provide a randomized comparison. The design does not establish what would have happened to comparable participants receiving another treatment. It cannot, on its own, support a causal estimate of a difference between treatment strategies.

The record’s safety entries describe participants affected by serious and other adverse events in the panitumumab group and list selected serious-event terms. They do not provide a control-group safety comparison. The record does not report a death count, and the listed terms do not represent a complete account of event timing or recurrence.

The findings that can be stated are therefore limited to the design, endpoint definition, treatment exposure summary, and posted safety counts. Results for the primary and secondary efficacy outcomes are not reported in the registry record. This absence should not be interpreted as evidence that the study observed no responses or no events; it means the relevant outcome values are not reported in the record.

14. Why This Trial Matters Statistically

This trial illustrates an important distinction between a clearly defined endpoint and a reported endpoint result. The registry record specifies objective response, the scan-based criteria, the confirmation requirement, and the analysis population. These details are necessary for interpreting a response estimate, but they do not tell readers what the estimate was. Statistical interpretation requires both a defined quantity and its observed value, together with information about uncertainty.

The study also provides a useful example of what a single-arm design can and cannot answer. A single treatment group can be used to describe outcomes among participants who received that treatment. It does not create a randomized counterfactual or a direct treatment comparison. When reviewing a single-arm response study, it is important to distinguish a descriptive response proportion from evidence about comparative benefit.

Endpoint denominators matter as well. The registry records enrollment of 52, while defining the primary endpoint population more narrowly as participants who received at least one dose and had measurable disease at baseline. The number in that population is not reported. Without the analysis denominator and response count, neither the response percentage nor its precision can be checked or interpreted.

Finally, safety summaries require careful reading. The registry lists participants affected by serious and other adverse events, along with selected serious-event terms and percentages. These entries provide some descriptive safety information, but they do not establish comparative risk, event causation, or the full distribution of event severity and timing. The record’s omissions are statistically meaningful: they set limits on the conclusions readers can draw, rather than inviting the missing results to be inferred.

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 objective response rate, response count, or 95% confidence interval. It also does not report numerical results for the listed secondary outcomes. Without these outcome results, the treatment-group response magnitude and its precision cannot be assessed.

The single-arm, open-label design has no concurrent comparator. It can describe outcomes within the treated group, but cannot provide a randomized comparison with another treatment. Investigator review of scans is specified, but independent central review, assessor blinding, and adjudication procedures are not reported in the registry record. No claim about how these features affected observed responses can be made from the record.

The full analysis set is defined by receipt of at least one dose and measurable disease at baseline, but its size is not reported. The record does not state how missing or unevaluable assessments were handled, how participants who did not complete follow-up were treated in the endpoint analysis, or whether subsequent therapy affected analysis beyond the endpoint’s stated timing rule. These details are not reported in the registry record.

The registry record does not report a sample-size justification for the trial, an interim-analysis plan, or a complete statistical analysis plan. It describes planning illustrations, but those assumptions do not establish the trial’s design rationale or its statistical methods. For safety, the record provides affected-participant counts and selected serious-event terms, but does not report a death count or detailed event-level information such as recurrence and timing. These limitations constrain interpretation without indicating what unreported results would have shown.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: PRISM (Panitumumab Regimen In Second-line Monotherapy of Head and Neck Cancer) — NCT00446446.
• Registry record last updated 2022-10-05; status last verified 2022-09.
• Results first posted 2016-03-07.
• 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

PRISM (NCT00446446) was a completed phase 2, open-label, multicenter, single-arm study sponsored by Amgen. It enrolled 52 participants with metastatic or recurrent squamous cell carcinoma of the head and neck. The study evaluated second-line panitumumab monotherapy, administered as an intravenous infusion at 9 mg/kg every 21 days until a specified stopping condition.

The primary endpoint was objective response rate in the defined full analysis set, assessed by investigator scan review using modified RECIST version 1.0. The registry record describes the response criteria and specifies a 95% confidence interval, but does not report the response estimate or interval. It lists 14 participants affected by serious adverse events and 50 affected by other adverse events, each among 52 at risk in the panitumumab group. A death count and numerical results for the listed secondary outcomes are not reported in the registry record.