This page provides an independent statistical analysis and educational interpretation of publicly reported results. ClinicalTrials.gov provides the official trial registry record. Numerical trial results on this page are restricted to the results posted in the ClinicalTrials.gov record; calculations added by Clinical Biostats are labelled as such.
1. Trial at a Glance
This page covers the registry results for Combination Chemotherapy With or Without Erlotinib Hydrochloride in Treating Patients With Metastatic or Recurrent Squamous Cell Carcinoma of the Head and Neck (NCT01064479), a randomized phase 2 study. The primary outcome is Progression Free Survival (PFS).
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT01064479 |
| Phase | Phase 2 |
| Condition | Metastatic Squamous Cell Carcinoma of the Hypopharynx, Metastatic Squamous Cell Carcinoma of the Larynx, Metastatic Squamous Cell Carcinoma of the Oral Cavity |
| Allocation | Randomized |
| Design model | Parallel |
| Masking | Double |
| Enrollment | 123 |
| Arms in the primary outcome | 2 |
| Lead sponsor | M.D. Anderson Cancer Center |
| Results posted | Yes |
2. Clinical Question
Population
People with metastatic or recurrent squamous cell carcinoma of the head and neck were eligible. The registry lists disease involving the hypopharynx, larynx, oral cavity, or oropharynx, including stage IV disease. The posted record reports total enrollment of 123, but does not provide a detailed account of participant characteristics or the analysis population.
Intervention
Arm A received docetaxel with cisplatin or carboplatin, together with erlotinib hydrochloride. The arm description specifies treatment in repeating 21-day courses, with chemotherapy and erlotinib schedules described in the registry. The full treatment description is truncated in the registry record, so additional details are not reported there.
Comparator
Arm B received docetaxel with cisplatin or carboplatin and placebo. This design keeps the chemotherapy backbone in both groups while varying the added oral treatment. The registry describes a randomized, double-masked, parallel-group comparison.
Primary question
The primary endpoint was progression-free survival (PFS), measured in months. The central question was whether the distribution of time until disease progression or death differed between the chemotherapy-plus-erlotinib arm and the chemotherapy-plus-placebo arm. The registry lists median PFS estimates with 95% confidence intervals for each arm. It does not report the planned between-arm hazard ratio or stratified log-rank test result, so the posted figures alone do not establish the result of that planned comparison.
3. Trial Design
This was a randomized, double-masked, parallel-group phase 2 trial sponsored by M.D. Anderson Cancer Center. The registry reports enrollment of 123. Participants were assigned to one of two groups: combination chemotherapy with erlotinib hydrochloride, or the same chemotherapy approach with placebo. The design therefore aimed to assess the added treatment in the context of a shared chemotherapy backbone, rather than compare chemotherapy with no chemotherapy.
The chemotherapy backbone included docetaxel and either cisplatin or carboplatin. The arm descriptions specify intravenous chemotherapy and daily oral erlotinib or placebo in repeating 21-day courses, for up to 6 courses, subject to disease progression and unacceptable toxicity. The descriptions are truncated in the registry record, so further details of treatment after those courses are not reported there.
The registry identifies PFS as the primary outcome and lists a timeframe of 5 years. The planned primary analysis description says Kaplan-Meier methods would summarize PFS, with a stratified log-rank test comparing the arms at a two-sided alpha of 0.10. It also says hazard ratios with 95% confidence intervals would be presented. The posted primary results give medians and confidence intervals by arm, but do not include those comparative test or hazard-ratio results.
Arm-specific primary outcome denominators are 60 for the erlotinib arm and 59 for the placebo arm. These denominators do not add up to the reported enrollment of 123; participant disposition and reasons for any difference are not reported in the registry record. The registry lists the trial as completed, with a start date of 2010-02-05 and primary completion date of 2020-11-03. It does not report additional details on recruitment, follow-up completeness, or analysis populations.
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: 123 participants registered-4 participants were inevaluable (2 refused not due to toxicity, 2 other).
Overall Study
| Stage | Arm A (Combination Chemotherapy and Erlotinib Hydrochloride) | Arm B (Combination Chemotherapy and Placebo) |
|---|---|---|
| STARTED | 60 | 59 |
| COMPLETED | 45 | 42 |
| NOT COMPLETED | 15 | 17 |
Reasons for not completing this period:
| Reason | Arm A (Combination Chemotherapy and Erlotinib Hydrochloride) | Arm B (Combination Chemotherapy and Placebo) |
|---|---|---|
| Death | 10 | 11 |
| Withdrawal by Subject | 2 | 2 |
| Disease progression | 1 | 1 |
| Toxicity | 1 | 1 |
| Other | 1 | 2 |
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.
| Characteristic | Unit | Arm A (Combination Chemotherapy and Erlotinib Hydrochloride) | Arm B (Combination Chemotherapy and Placebo) | Total |
|---|---|---|---|---|
| Participants analysed | 60 | 59 | 119 | |
| Age, Categorical: <=18 years | Participants | 0 | 0 | 0 |
| Age, Categorical: Between 18 and 65 years | Participants | 52 | 51 | 103 |
| Age, Categorical: >=65 years | Participants | 8 | 8 | 16 |
| Sex: Female, Male: Female | Participants | 13 | 14 | 27 |
| Sex: Female, Male: Male | Participants | 47 | 45 | 92 |
| Race (NIH/OMB): American Indian or Alaska Native | Participants | 0 | 0 | 0 |
| Race (NIH/OMB): Asian | Participants | 2 | 1 | 3 |
| Race (NIH/OMB): Native Hawaiian or Other Pacific Islander | Participants | 0 | 0 | 0 |
| Race (NIH/OMB): Black or African American | Participants | 2 | 4 | 6 |
| Race (NIH/OMB): White | Participants | 51 | 49 | 100 |
| Race (NIH/OMB): More than one race | Participants | 0 | 0 | 0 |
| Race (NIH/OMB): Unknown or Not Reported | Participants | 5 | 5 | 10 |
| Region of Enrollment: United States | participants | 60 | 59 | 119 |
6. Primary Endpoint
The registry lists the primary outcome as Progression Free Survival (PFS), measured over 5 years.
| Element | Registry entry |
|---|---|
| Result type | Median |
| Measure of spread | 95% Confidence Interval |
| Unit | months |
| Endpoint classification | Time-to-Event Analysis |
Progression-free survival is a time-to-event endpoint. In general, it represents the time from a defined starting point until disease progression or death, according to the trial’s endpoint definitions. The registry identifies PFS as the primary endpoint and reports it in months. The exact operational definitions of progression, the starting point for measuring time, and assessment procedures are not reported in the registry record.
A time-to-event measure can use information about both whether an event occurred and when it occurred. Kaplan-Meier methods, named in the registry’s planned analysis, estimate the event-free distribution over time while accounting for participants whose event time is not observed during follow-up. The median is the time at which the estimated proportion remaining free of the event reaches the midpoint of that distribution. It is a summary of the estimated timing, not a description of every participant’s experience.
PFS is useful in a trial because it captures disease progression as well as death, rather than relying only on survival. However, a median by itself is not a complete comparison of the arms. It does not show the shape of the time-to-event distributions or account for all follow-up information in a comparative model. The registry’s planned log-rank test and hazard ratio were intended to address the between-arm comparison, but their results are not reported. Therefore, the arm-specific medians and confidence intervals can be described, while the planned comparative result remains unavailable in the registry record.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The posted primary results report median PFS of 6.08 months in the combination chemotherapy and erlotinib arm, with a 95% confidence interval from 5.45 to 7.52 months. In the combination chemotherapy and placebo arm, median PFS is 4.4 months, with a 95% confidence interval from 3.45 to 5.78 months. These are separate arm-level estimates. The registry does not report the hazard ratio, its confidence interval, or the stratified log-rank test result specified in the planned analysis description.
A median describes the estimated time by which half of the relevant event-time distribution has occurred. It does not mean that all participants had an event at that time, and it does not tell how far apart the arms are across the entire follow-up period. The confidence intervals express uncertainty around each arm’s median estimate. They should not be treated as a substitute for the direct statistical comparison between arms.
The planned analysis used a two-sided alpha of 0.10 for the stratified log-rank test. Since the registry does not post the test result, it is not possible to determine from the primary results whether that planned test met its stated threshold. Nor is it possible to assess the size and precision of the relative event-rate estimate, because no hazard ratio or confidence interval for that estimate is posted. The fact that two arm-specific medians are reported does not fill these gaps.
The registry’s primary description says that Kaplan-Meier methods would summarize PFS. In general, these methods use observed event times and account for censoring, which occurs when the event is not observed for a participant during the available follow-up. The record does not provide the number of events, numbers censored, follow-up distribution, or further details needed to evaluate how the estimates were supported. Those details are not reported in the registry record.
The displayed medians are descriptive evidence about the recorded trial results, but they do not by themselves show that adding erlotinib caused a change in PFS. Randomization supports a fair comparison in principle, yet interpretation also depends on the analysis, completeness of outcome data, and uncertainty in the between-arm estimate. With the planned comparative statistic absent, the posted primary results provide less information than the analysis plan says would be reported. No treatment recommendation follows from these figures alone.
9. Statistical Methods Explained
General: What does a median PFS estimate mean? For a time-to-event outcome, the median is a point on the estimated event-time distribution. It marks the time by which an estimated half of the population has experienced progression or death, under the endpoint definition used in the trial. It is not the average time to an event, and it does not imply that each participant’s course was close to the median. In this trial, the registry reports median PFS of 6.08 months for the erlotinib arm and 4.4 months for the placebo arm.
General: Why use Kaplan-Meier methods? Kaplan-Meier estimation is commonly used for time-to-event outcomes because not every participant’s event time is necessarily observed. A participant may leave observation or reach the end of available follow-up without a recorded event; that observation is censored at the last known time. The method incorporates the event times and censoring information into an estimated survival curve. The registry says Kaplan-Meier methods would be used, but does not report the number of events, censoring details, or estimated curves in the posted primary results.
General: What information does a confidence interval provide? A confidence interval describes the uncertainty associated with an estimate under the statistical method used. The primary results give 95% confidence intervals for each arm’s median: 5.45 to 7.52 months for the erlotinib arm and 3.45 to 5.78 months for the placebo arm. These intervals apply to the separate median estimates. They are not a confidence interval for the difference between arms or for a hazard ratio. A direct comparative interval would be needed to express uncertainty around a relative treatment contrast.
What was the planned comparison? The registry describes a stratified log-rank test comparing PFS in Arm A versus Arm B, with a two-sided alpha of 0.10. In general, a log-rank test compares time-to-event patterns across groups while accounting for the timing of events and censoring. Stratification can account for prespecified grouping factors in the comparison. The stratification factors are not reported in the registry record. The test result is also not reported, so the planned comparison cannot be evaluated from the posted primary values alone.
The record also says that hazard ratios for PFS would be presented as point estimates with 95% confidence intervals. A hazard ratio is a relative summary of event rates over follow-up, subject to assumptions about how those rates compare over time. It is not the same quantity as a ratio of medians. Neither the planned hazard-ratio estimate nor its confidence interval is reported. The registry’s statement of planned methods should therefore be kept distinct from the numerical results that are actually posted.
General: Why can over-dispersion matter? In some outcomes, participant-level observations vary more than a simple statistical model expects. This extra variability, often called over-dispersion, can make standard errors too small if the model does not account for it. That concern is relevant to some count or clustered-data analyses, but the registry’s posted primary endpoint is time-to-event PFS, and the primary results do not describe an over-dispersion model. The analysis details needed to assess additional modeling assumptions are not reported in the registry record.
How should secondary planning illustrations be read? The posted secondary outcome calculations include illustrative sample-size estimates based on observed effects, with a two-sided significance level of 0.05, equal allocation, and a normal approximation. Such calculations are planning illustrations, not evidence about the trial’s achieved power and not the trial’s own sample-size justification. They show how a future study’s planned size could depend on the effect it aims to detect. Smaller assumed effects require larger samples in those illustrations. The registry’s own design rationale and sample-size justification are not reported. No time-to-event planning illustration is available for the primary endpoint in the posted calculations.
General: Why are unadjusted secondary tests less conclusive? When several outcomes are examined, each test creates an opportunity for a chance finding. If results are interpreted without accounting for the number or order of comparisons, a nominal p-value can overstate the strength of evidence. Adjustment strategies or a prespecified hierarchy can address this issue, but the registry does not report such a strategy for the secondary outcomes. The posted secondary comparisons are unadjusted recalculations from summary counts, not sponsor-reported analyses; they should be treated as exploratory rather than as substitutes for a complete prespecified analysis.
10. Multiplicity, Missing Data and Analysis Populations
The registry lists multiple outcomes: PFS as primary, with overall survival, tumor response, disease control, and rash rates as secondary outcomes. The registry does not report whether the secondary outcomes were tested under a prespecified hierarchy, whether any multiplicity adjustment was used, or how confirmatory and exploratory analyses were distinguished in the protocol. Without that information, the secondary findings should not be interpreted as if each were an independently confirmatory test.
The primary analysis description does specify a stratified log-rank test with a two-sided alpha of 0.10. However, the result of that test and the planned hazard ratio with its confidence interval are not reported. The registry also does not describe whether other primary analyses, sensitivity analyses, or interim analyses were conducted. These details are not reported in the registry record and should not be inferred from the posted arm-level medians.
Information about missing outcome data and analysis populations is limited. The record reports enrollment of 123, while the primary outcome denominators are 60 and 59. Participant disposition, reasons for the difference, and whether all randomized participants were included in the primary analysis are not reported. The registry does not state whether the analysis followed an intention-to-treat principle, how censoring was handled in practice, or how missing assessments were addressed.
These omissions matter because analysis choices can affect estimates and their uncertainty. For PFS, follow-up and censoring information help readers understand which event-time data contribute to the estimates. For binary outcomes, analysis denominators and missing-data handling clarify which participants contribute to each count. The absence of these details does not prove that the analyses were inappropriate; it limits what can be independently assessed from the registry record.
11. Safety Results
The registry reports serious adverse events as affected participants divided by participants at risk.
| Arm | Participants with serious adverse events | Participants at risk | Percentage |
|---|---|---|---|
| Arm A (Combination Chemotherapy and Erlotinib Hydrochloride) | 21 | 60 | 35.0% |
| Arm B (Combination Chemotherapy and Placebo) | 46 | 59 | 78.0% |
Deaths
| Arm | Deaths (participants affected of at risk) |
|---|---|
| Arm A (Combination Chemotherapy and Erlotinib Hydrochloride) | 37 of 60 |
| Arm B (Combination Chemotherapy and Placebo) | 53 of 59 |
Other (non-serious) adverse events
Participants with at least one non-serious event at or above the registry's 5% reporting threshold.
| Arm | Participants affected of at risk |
|---|---|
| Arm A (Combination Chemotherapy and Erlotinib Hydrochloride) | 56 of 60 |
| Arm B (Combination Chemotherapy and Placebo) | 55 of 59 |
Most frequent serious adverse event terms
| Event term | Organ system | Arm A (Combination Chemotherapy and Erlotinib Hydrochloride) | Arm B (Combination Chemotherapy and Placebo) |
|---|---|---|---|
| Dehydration | Gastrointestinal disorders | 8 of 60 | 5 of 59 |
| Lung infection | Infections and infestations | 7 of 60 | 5 of 59 |
| Sepsis | Infections and infestations | 5 of 60 | 2 of 59 |
| Nausea | Gastrointestinal disorders | 4 of 60 | 2 of 59 |
| Diarrhea | Gastrointestinal disorders | 5 of 60 | 1 of 59 |
| Anemia | Blood and lymphatic system disorders | 3 of 60 | 3 of 59 |
| Febrile neutropenia | Blood and lymphatic system disorders | 3 of 60 | 2 of 59 |
| Aspiration | Respiratory, thoracic and mediastinal disorders | 2 of 60 | 3 of 59 |
| Abdominal pain | Gastrointestinal disorders | 3 of 60 | 1 of 59 |
| Hypotension | Vascular disorders | 2 of 60 | 1 of 59 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Arm A (Combination Chemotherapy and Erlotinib Hydrochloride) | Arm B (Combination Chemotherapy and Placebo) |
|---|---|---|---|
| Diarrhea | Gastrointestinal disorders | 46 of 60 | 30 of 59 |
| Fatigue | General disorders | 40 of 60 | 33 of 59 |
| Nausea | Gastrointestinal disorders | 38 of 60 | 27 of 59 |
| Rash maculo-papular | Skin and subcutaneous tissue disorders | 35 of 60 | 12 of 59 |
| Rash acneform | Skin and subcutaneous tissue disorders | 31 of 60 | 10 of 59 |
| Dry skin | Skin and subcutaneous tissue disorders | 22 of 60 | 13 of 59 |
| Mucositis oral | Gastrointestinal disorders | 16 of 60 | 17 of 59 |
| Vomiting | Gastrointestinal disorders | 23 of 60 | 10 of 59 |
| Oral pain | Gastrointestinal disorders | 11 of 60 | 12 of 59 |
| Anorexia | Metabolism and nutrition disorders | 14 of 60 | 7 of 59 |
Serious events with the highest arm-level rate: dehydration (13.3%), lung infection (11.7%), diarrhea (8.3%), sepsis (8.3%), nausea (6.7%).
The registry reports serious adverse events in 21 of 60 participants in the erlotinib arm and 46 of 59 participants in the placebo arm. It also reports other adverse events in 56 of 60 and 55 of 59 participants, respectively. These are participant counts, not counts of separate episodes. The registry lists deaths in 37 participants in the erlotinib arm and 53 in the placebo arm; these figures alone do not establish cause or relationship to treatment.
Serious adverse-event terms listed include dehydration at 13.3%, lung infection at 11.7%, diarrhea at 8.3%, sepsis at 8.3%, nausea at 6.7%, and anemia at 5.1%. The registry record does not provide enough context in the posted figures to interpret these percentages as a complete arm-by-arm comparison. It also does not report event timing, exposure-adjusted rates, duration, severity grades for each event, or attribution to study treatment in these summary figures.
Safety counts describe events recorded during the study and should be interpreted with the study population, follow-up, and event definitions in mind. They do not by themselves establish that a treatment caused an event or provide a complete comparison of safety. The detailed definitions and additional safety-analysis methods are not reported in the registry record.
12. What the Result Does, and Does Not, Mean
The posted results describe a randomized comparison of combination chemotherapy with erlotinib against combination chemotherapy with placebo. For the primary endpoint, the registry reports arm-specific median PFS estimates and 95% confidence intervals. Those figures provide descriptive information about estimated event timing in each group, but the planned comparative hazard ratio and stratified log-rank test result are not posted.
That distinction limits what can be concluded statistically. A difference between arm-level summaries is not the same as a reported estimate of the treatment contrast, and separate confidence intervals do not quantify uncertainty in that contrast. The absent hazard ratio and test result mean that the main planned inferential comparison cannot be assessed from the registry results alone. The posted values also do not describe all aspects of the PFS curves or participant follow-up.
The secondary results add context but do not replace the primary analysis. Numerical results are available for disease control and rash rates, while results for overall survival and tumor response are not reported in the registry record. The available secondary comparisons are unadjusted recalculations from summary counts, and the registry does not describe a multiplicity plan. They therefore warrant cautious, exploratory interpretation.
These findings do not establish whether one treatment approach is preferable, and they should not be used as individual medical advice. They also do not establish that any observed outcome was caused by the added erlotinib. Randomization is a strength of the design, but a complete interpretation depends on the comparative analysis, data completeness, and methods that are not fully reported in the registry.
The trial is best understood as a phase 2 randomized study with a clearly stated PFS objective and incomplete posted inferential results. The medians can be quoted as the registry’s reported arm estimates; the uncertainty and significance of the between-arm comparison remain unresolved in the posted record.
13. Why This Trial Matters Statistically
This trial is statistically informative as an example of why an endpoint’s arm-specific summaries and its comparative analysis answer different questions. A median PFS describes each arm separately. The planned stratified log-rank test and hazard ratio would address how the time-to-event experience compares between arms. When the comparative result is absent, readers cannot substitute a visual or numerical contrast between medians for the intended inferential analysis.
The design also illustrates the value of a randomized, double-masked, placebo-controlled structure when the aim is to evaluate the addition of one agent to a shared chemotherapy backbone. Random allocation can support comparable groups on average, and masking can reduce some sources of bias. Those design features do not remove the need for transparent reporting of analysis populations, follow-up, censoring, and comparative estimates.
The registry provides a declared primary analysis approach, including Kaplan-Meier summaries and a stratified log-rank test, while the posted primary results include only median estimates and confidence intervals. That gap is important for statistical literacy: a method described in advance is not itself evidence that its result favored either arm. Readers need the estimate, its uncertainty, and the test result to assess the stated comparison.
Finally, the registry lists several secondary outcomes but reports numerical results for only some of them. Unadjusted secondary comparisons can be useful for describing patterns and generating questions, but they have less confirmatory force when multiplicity handling and analysis plans are not reported. The record thus demonstrates the importance of distinguishing design, planned methods, posted estimates, and conclusions that the available evidence can support.
14. Limitations
- The posted summary statistics are the only data these results rest on; patient-level data, full protocols and statistical analysis plans are not available.
- Recalculated results are simple, unadjusted calculations from posted summaries. They do not replace the sponsor's prespecified analysis.
Several trial-specific reporting gaps constrain interpretation. The registry reports total enrollment of 123, whereas the arm denominators for PFS are 60 and 59. A participant flow account, reasons for this difference, and the populations included in each analysis are not reported. It is therefore not possible to determine from the posted information how enrollment translated into the primary analysis set.
The primary endpoint has arm-specific medians and 95% confidence intervals, but the planned comparative hazard ratio and stratified log-rank test result are not posted. The registry’s description does not identify the stratification factors. Nor does it report event counts, censoring information, follow-up distribution, or details of outcome assessment. These omissions limit assessment of the time-to-event analysis and its precision.
Although several secondary outcomes are listed, numerical results are available only for disease control and rash rates in the posted results. Overall survival and tumor response results are not reported in the registry record. Multiplicity handling, secondary analysis plans, and whether these outcomes were treated as exploratory or confirmatory are also not reported. The unadjusted comparisons recalculated from summary counts cannot resolve those gaps.
The treatment descriptions in the registry are truncated, and further treatment details are not reported there. Participant characteristics, detailed eligibility criteria, sample-size justification, missing-data methods, and analysis-population definitions are also not reported. The serious adverse-event summary does not provide event timing, attribution, or exposure-adjusted rates. These limitations do not establish that the underlying trial lacked such procedures; they define what cannot be evaluated from the registry record.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Combination Chemotherapy With or Without Erlotinib Hydrochloride in Treating Patients With Metastatic or Recurrent Squamous Cell Carcinoma of the Head and Neck — NCT01064479.
- Registry record last updated 2024-07-16; status last verified 2024-07.
- Results first posted 2022-01-25.
- 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.
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18. Record Summary
NCT01064479 is a completed randomized, double-masked, parallel-group phase 2 trial sponsored by M.D. Anderson Cancer Center. It enrolled 123 participants with metastatic or recurrent squamous cell carcinoma of the head and neck. The comparison was docetaxel with cisplatin or carboplatin plus erlotinib hydrochloride versus the chemotherapy backbone plus placebo.
PFS was the primary endpoint. The registry reports median PFS of 6.08 months (95% CI 5.45 to 7.52) in the erlotinib arm and 4.4 months (95% CI 3.45 to 5.78) in the placebo arm. The planned hazard ratio and stratified log-rank test result are not reported. Numerical secondary results are posted for disease control and rash rates; results for overall survival and tumor response are not reported in the registry record. Missing details on analysis populations, participant disposition, and multiplicity further limit interpretation.