Cetuximab + / - Carboplatin for Estrogen Receptor-Negative, Progesterone Receptor-Negative Metastatic Breast Cancer: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Cetuximab + / - Carboplatin for Estrogen Receptor-Negative, Progesterone Receptor-Negative Metastatic Breast Cancer (NCT00232505), a randomized phase 2 study. The primary outcome is Overall Disease Response Rate.

2. Clinical Question

The trial rationale was to compare the combination with cetuximab alone in this population. The primary endpoint description includes complete response, partial response, stable disease, and progressive disease. It says radiographic assessment was planned every 8 weeks until disease progression, and gives a timeframe of 5 years. How the categories were converted into the overall response rate used for a group comparison is not reported in the registry record.

3. Trial Design

This was a randomized, single-masked, parallel-group phase II trial. The registry record lists an enrollment of 112 and describes two initial treatment assignments: cetuximab alone or cetuximab with carboplatin. Details about the randomization procedure, allocation concealment, and who was masked are not reported in the registry record.

The cetuximab-only arm could lead to crossover: patients not responding to treatment could move to the combination arm. The adverse-event record separately lists a group titled “Cetuximab and Carboplatin After Cetuximab Alone.” This treatment history matters when reading safety counts because that group is not simply the original combination assignment. The registry record does not report how crossover was handled in the primary efficacy analysis.

The combination regimen added intravenous carboplatin on days 1, 8, and 15 to the weekly cetuximab regimen; each description says treatment repeated every 28 days unless progression or unacceptable toxicity occurred. The trial status is completed. The record lists a start of 2005-11 and primary completion on 2010-06-21.

The record names overall disease response rate as the primary outcome and overall survival and progression-free survival as secondary outcomes. It gives the response outcome a timeframe of 5 years, while also describing radiographic assessments every 8 weeks until progression. Detailed follow-up rules, endpoint analysis methods, and the planned statistical analysis are not reported in the registry record. The enrollment figure alone does not establish how many participants were included in any outcome analysis or how many were assigned to each initial arm.

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: Four patients declined participation for personal reasons, three were screen failures, three had death or progression during the screening period.

Overall Study

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 Overall Disease Response Rate, measured over 5 years.

The primary endpoint is overall disease response rate, recorded in participants and assessed by radiographic imaging using RECIST. The description distinguishes complete response, partial response, stable disease, and progressive disease. Complete response is disappearance of all target lesions. Partial response is at least a 30% decrease in the sum of the longest diameters of target lesions. Progression is a 20% increase in that sum, a measurable increase in a non-target lesion, or the appearance of new lesions. Stable disease is neither sufficient shrinkage for partial response nor sufficient increase for progression.

Response endpoints are used to describe whether measurable disease changes under treatment, rather than relying only on time until an event. A radiographic rule can make assessments more consistent by defining what counts as response or progression. In general, however, a response rate depends on the analysis rule that determines which categories count as responses and which participants are included. The registry record does not specify how its four listed categories were combined to calculate the overall response rate, nor does it report category counts or response results.

The outcome description says imaging was assessed every 8 weeks until progression, and lists a timeframe of 5 years. It does not report the observed assessment schedule or the results at any assessment. Overall survival and progression-free survival are listed as secondary outcomes, but their outcome results are not reported in the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry identifies the study as randomized, single-masked, and parallel-group. In general, random assignment is intended to make the assigned groups comparable, on average, at the start of a trial. A parallel-group design assigns participants to a treatment strategy for comparison. Masking can reduce the influence of knowledge about assignment on care or assessment, depending on who is masked. The record does not say who was masked, how assignment was generated or concealed, or how the primary outcome was analyzed, so those design details cannot be evaluated from the registry entry.

What does a response count represent?

The primary outcome is described as a count of participants, and its meaning is participants with an event (counts). Here, the event is related to the response categories assessed under RECIST. For a binary endpoint, an analysis commonly distinguishes participants meeting a defined response rule from those who do not. In general, a response proportion is interpretable only when the response rule, analysis population, and handling of participants without an evaluable assessment are clear. The registry lists complete response, partial response, stable disease, and progressive disease but does not state the exact rule used to turn these categories into the overall response rate. It also provides no response counts.

How should a treatment contrast be read?

In general, a treatment comparison for a binary outcome can report a difference between group proportions, a ratio of proportions, or another prespecified measure. These summaries answer different questions and should be interpreted with their uncertainty. A confidence interval describes a range of effect values compatible with the data and model assumptions; narrower intervals indicate greater precision. A p-value describes how compatible the observed data are with a specified null hypothesis under the analysis assumptions. Neither a confidence interval nor a p-value is reported for the primary outcome in this registry record, and no treatment contrast can be reconstructed without group outcome data.

The outcome description gives RECIST rules for target and non-target lesions. It defines complete response as disappearance of all target lesions; partial response as at least a 30% decrease in the sum of the longest diameters of target lesions; and progression as a 20% increase in that sum, a measurable increase in a non-target lesion, or new lesions. Stable disease is the category that meets neither the partial-response nor progression definition. In general, using explicit criteria can standardize classification, but assessment still depends on the imaging schedule, evaluability, and rules for handling incomplete observations. Those operational details are not reported in the registry record beyond the stated assessment schedule and endpoint description.

What can the planning assumptions tell us?

The record describes a planning illustration based on the observed effect, not the trial's own design. Its stated assumptions are a two-sided significance level of 0.05, equal allocation between the two arms, and a normal approximation; the effect to detect is a stated fraction of the observed effect. In general, sample-size planning asks how much information a future study would need to detect a specified effect under chosen assumptions. Such an illustration is not an observed result, does not establish the design used for this trial, and is not observed power. The numerical planning outputs are not reported in the registry record. No sample-size justification for the actual trial is reported.

What is missing from the analysis record?

The registry record reports zero outcome analyses. This means no outcome analysis is presented in the record; it does not establish whether analyses were conducted outside the registry. The statistical model, covariate adjustment, confidence-interval method, missing-data approach, and analysis population are not reported. In general, those choices affect how a trial estimate is produced and interpreted. The crossover option is especially relevant because an analysis by initial assignment and an analysis based on treatment received answer different questions. The registry record does not describe which approach, if any, was used.

10. Multiplicity, Missing Data and Analysis Populations

The record lists one primary outcome, overall disease response rate, and two secondary outcomes, overall survival and progression-free survival. It does not report a multiplicity plan, such as how inference across several outcomes or comparisons was handled. In general, testing multiple outcomes can increase the chance of at least one apparently unusual result when all are interpreted as confirmatory. A prespecified strategy can distinguish primary from supportive analyses and clarify how uncertainty is controlled. The registry record does not describe such a strategy, and it reports no outcome analyses or inferential results.

Missing-data methods are also not reported. The endpoint description states that radiographic assessments were planned every 8 weeks until progression, but the record does not give the number of missing or unevaluable assessments, reasons for missingness, or any imputation or censoring rules. In general, missing outcome information can affect an estimate if the participants with observed assessments differ from those without them. The extent and direction of any such effect cannot be assessed without the missingness and analysis details.

The analysis populations are not specified. The record does not say whether the primary analysis included participants according to initial randomized assignment, treatment received, or another eligibility rule. This is important because patients not responding to cetuximab alone could cross over to the combination arm. An analysis based on initial assignment and one based on treatment actually received may address different questions. The registry record does not explain how this crossover was incorporated into efficacy analyses.

11. 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 1% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: allergic reaction/hypersensitivity (including drug fever) (12.0%), dyspnea (shortness of breath) (9.9%), anorexia (8.0%), pain - other (specify, __) (8.0%), seizure (8.0%).

The registry lists serious adverse-event participant counts by treatment group. For cetuximab, it records 3 affected among 31 at risk. For “Cetuximab and Carboplatin After Cetuximab Alone,” it records 8 affected among 25 at risk. For “Cetuximab and Carboplatin,” it records 20 affected among 71 at risk. The record also lists other adverse-event counts: 27 among 31 for cetuximab, 24 among 25 for the post-cetuximab combination group, and 68 among 71 for the combination group. These are recorded counts, not a comparative analysis.

The post-cetuximab combination group has a different treatment history from the group initially assigned to the combination. It should not be treated as a separate randomized comparison arm. The record does not provide details about exposure duration, event timing, severity criteria, attribution, or adjustment for follow-up. Those details limit interpretation of comparisons across the listed groups.

The registry lists serious adverse-event terms with percentages: allergic reaction/hypersensitivity (including drug fever), 12.0%; dyspnea (shortness of breath), 9.9%; anorexia, 8.0%; pain, 8.0%; seizure, 8.0%; and limb edema, 6.5%. The denominator and calculation details for these term percentages are not reported in the registry record. These figures should be read as registry safety reporting, not as proof that a treatment caused an event or as a direct comparison of treatment risks.

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

The registry record identifies a randomized phase II comparison of cetuximab alone with cetuximab plus carboplatin in ER-negative, PR-negative metastatic breast cancer; the official title also specifies HER-2 nonoverexpressing disease. It describes radiographic response criteria and lists survival outcomes as secondary. Those details clarify what the study set out to assess, but they do not supply the outcome evidence needed to quantify the comparison.

No primary response counts, group response estimates, or comparative analysis are reported in the registry record. Consequently, the posted results do not establish the size, direction, or precision of a response difference. They also do not establish that the treatments had the same response results. An unavailable result is not evidence of no difference, and the completed status does not fill that evidentiary gap.

The registry record does include adverse-event counts and selected serious-event terms, but these are presented across groups with different treatment histories, including a group that received combination treatment after cetuximab alone. Without reported exposure, follow-up, and comparative analysis details, the counts do not support a causal comparison of safety between the randomized assignments.

In general, a trial result is interpreted in light of its endpoint definition, analysis population, statistical method, uncertainty, and missing data. Here, several of those elements are not reported, and the outcome analyses are absent from the registry record. The trial therefore documents a clinical question and selected descriptive information, but the posted results do not provide a numerical answer to that question. No treatment recommendation follows from these registry data alone.

13. Why This Trial Matters Statistically

This trial is statistically informative as an example of why a registry entry’s design and outcome listings must be distinguished from an analyzed result. Randomization and a named primary endpoint describe the intended comparison, but interpretation requires the observed outcome data and a transparent analysis. For this trial, the registry record gives neither primary response counts nor an outcome analysis, so the central comparison cannot be quantified.

The response endpoint also illustrates the importance of a precise estimand: the exact outcome being compared, for which participants, and under what treatment strategy. The record describes four radiographic categories and allows crossover from cetuximab alone for patients not responding, but it does not state how the categories were converted into the overall response rate or how crossover was handled in the primary analysis. Those choices can change the question answered by an analysis.

The safety reporting offers a related lesson. Counts are listed for the initial cetuximab group, the initial combination group, and a post-cetuximab combination group. Keeping randomized assignments distinct from later treatment histories is necessary for a fair reading. A list of counts does not, by itself, estimate a causal difference or account for exposure and follow-up.

Finally, the record’s planning assumptions are identified as an illustration rather than the trial’s design. In general, planning calculations are conditional on assumptions and should not be confused with observed evidence or observed power. This distinction is important when reading any sample-size illustration alongside a trial record. Here, the available registry information supports careful description of design and reporting, while leaving the efficacy comparison unresolved.

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.

The main limitation of the registry record for interpreting efficacy is that it does not report primary response results or outcome analyses. There are no response counts by randomized assignment, no group estimates, and no uncertainty measure for the primary comparison. Overall survival and progression-free survival are listed as secondary outcomes, but their results are not reported either.

The record does not give arm-specific enrollment or the number analyzed for each outcome. It does not report participant flow, missing or unevaluable imaging, or how such observations were handled. Although imaging was described as occurring every 8 weeks until progression and the outcome timeframe is listed as 5 years, observed follow-up and endpoint assessment details are not reported.

The response description lists RECIST categories and definitions, but does not state the operational rule used to calculate overall response rate from those categories. Details of the randomization process, masking, analysis populations, statistical model, covariate adjustment, and multiplicity handling are also not reported. The permitted crossover from cetuximab alone adds an interpretation issue, and the registry record does not explain its treatment in efficacy analyses.

The safety record provides counts for groups with different treatment histories, but does not report event timing, exposure duration, attribution, or a comparative safety analysis. It also does not give the denominator or calculation method for the listed serious-event term percentages. These gaps limit what can be concluded from the posted safety information; they do not establish that an analysis or detail was absent outside the registry record.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Cetuximab + / - Carboplatin for Estrogen Receptor-Negative, Progesterone Receptor-Negative Metastatic Breast Cancer — NCT00232505.
• Registry record last updated 2017-06-28; status last verified 2017-05.
• Results first posted 2017-06-28.
• 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.

18. Record Summary

NCT00232505 is a completed randomized, single-masked, parallel-group phase II trial sponsored by UNC Lineberger Comprehensive Cancer Center. It studied cetuximab alone and cetuximab plus carboplatin in metastatic breast cancer that was ER-negative and PR-negative; the official title also specifies HER-2 nonoverexpressing disease. The registry lists enrollment of 112.

The primary outcome was overall disease response rate, assessed radiographically using RECIST. Overall survival and progression-free survival were listed as secondary outcomes. Patients in the cetuximab-only arm who did not respond could cross over to the combination arm.

The registry record does not report primary response results, secondary outcome results, or outcome analyses. It does list adverse-event counts and selected serious-event terms, but these do not supply a comparative efficacy estimate or a complete safety comparison.