1303GCC: Trastuzmab & Pertuzumab With Hormonal Therapy or Chemotherapy in Women Aged 60 and Over.: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for 1303GCC: Trastuzmab & Pertuzumab With Hormonal Therapy or Chemotherapy in Women Aged 60 and Over. (NCT02000596), a non-randomized phase 2 study. The primary outcome is Overall Response Rate (ORR) in Patients.

2. Clinical Question

The study concerned women aged 60 and over with HER2/neu-overexpressed locally advanced and/or metastatic breast carcinoma. The registry identifies metastatic breast cancer as the condition and describes trastuzumab plus pertuzumab as the treatment used in the initial cohort. The study question was whether this combination, alone and with additional hormonal therapy or chemotherapy in later treatment, could be evaluated in this population.

The treatment pathway is important to interpreting the question. Cohort 2 Arm A and Cohort 2 Arm B were options for participants who progressed on trastuzumab plus pertuzumab alone; the additional treatment depended on ER/PR status. The endpoint population is specified as continuing into Arm B, not as all participants enrolled or everyone treated in every cohort. Therefore, the primary endpoint does not by itself describe response across the full study population.

3. Trial Design

The registry classifies the study as phase II, non-randomized, unmasked, and single group. Enrollment was 2. The study began in 2014-01, had a primary completion date of 2015-11, and is listed as terminated. A reason for termination is not reported in the registry record.

The treatment strategy began with trastuzumab plus pertuzumab as first-line treatment for HER2-overexpressed metastatic breast cancer. For participants who progressed on that combination, the registry describes two treatment pathways: anastrozole and fulvestrant in addition to trastuzumab plus pertuzumab for those who were ER/PR positive, or eribulin in addition to trastuzumab plus pertuzumab for those who were ER/PR negative. These descriptions define treatment stages and eligibility conditions; they do not establish that participants were randomized between the options.

Because allocation was non-randomized and the design is listed as single group, the cohorts should not be interpreted as randomized comparison arms. The registry explicitly cautions that the groups are not a like-for-like control comparison. Differences in participants’ disease course and eligibility for later treatment could affect who appears in each cohort. The progression-based pathway also means a participant could move from the initial treatment cohort to a later treatment cohort.

The registry lists overall response rate as the primary outcome, with progression-free survival, overall survival, treatment-related adverse events, and quality of life via patient-reported outcomes among the secondary outcomes. The registry record does not report a sample-size justification, detailed statistical analysis plan, or reason for the enrollment of 2. Further design details beyond the classifications and treatment descriptions 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.

Cohort 1

Cohort 2

Analysis population for the primary outcome, as defined in the registry: Participants started in "Cohort 1: T+P" Arm/Group and continued in "Cohort 2 Arm B" due to progressive disease

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.

Population: Participants started in "Cohort 1: T+P" Arm/Group and continued in "Cohort 2 Arm B" due to progressive disease

6. Primary Endpoint

The registry lists the primary outcome as Overall Response Rate (ORR) in Patients, measured over Participants were staged every two cycles for the duration of the study participation ( CR+PR+SD=ORR), up to 11 months.

The primary endpoint is titled overall response rate in patients and is measured as a count of participants. The registry defines it as the total of complete response, partial response, and stable disease among the total number of participants in the specified population. Complete response is described as disappearance of all target lesions. Partial response is defined as at least 30% decrease in the sum of the longest diameter of target lesions. Stable disease is defined as lasting at least 27 weeks. The registry attributes these response criteria to RECIST 1.1.

Participants were staged every two cycles for the duration of study participation, up to 11 months. The registry’s endpoint population is participants who started in Cohort 1 and continued in Cohort 2 Arm B because of progressive disease. This population definition matters: the outcome is not presented as a response count for everyone enrolled or for all treatment cohorts combined.

As a general statistical concept, response endpoints provide a categorical summary of participants’ observed disease status under a defined assessment rule. They can be useful when the question concerns whether participants meet specified response categories during a stated observation period. Their interpretation depends on consistent assessment, the population included, and the exact endpoint definition. Here, the registry’s stated definition includes complete response, partial response, and stable disease; interpretation should follow that record-specific definition rather than substituting a different convention.

A numerical primary endpoint result is not reported in the registry record. Consequently, the endpoint definition can be described, but the recorded information does not establish how many participants met it.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

Statistical interpretation begins with the design. This study is classified as non-randomized and single group, with no masking. In general, random assignment helps balance measured and unmeasured participant characteristics across treatment groups. Without it, observed differences between cohorts can reflect who entered each cohort, their disease course, or eligibility criteria, as well as treatment. In this study, the later treatment pathways explicitly depend on progression and ER/PR status, so the cohorts do not function as randomized controls.

What does the endpoint count?

The primary endpoint is a count of participants meeting the registry’s response definition. The record combines complete response, partial response, and stable disease. Complete response means disappearance of all target lesions; partial response means at least 30% decrease in the sum of the longest diameter of target lesions; stable disease means at least 27 weeks. These categories are attributed to RECIST 1.1. The stated evaluation schedule is every two cycles, for the duration of participation, up to 11 months.

As a general statistical point, an endpoint definition determines which observations count as events and the population over which they are counted. A count alone does not communicate the frequency of an outcome unless its denominator and analysis population are also clear. In this record, the primary population is described as participants who started in Cohort 1 and continued in Cohort 2 Arm B after progressive disease. The registry does not report a numerical response result, so neither the event count nor a response proportion can be interpreted from the recorded endpoint definition alone.

How should a confidence interval be understood?

In general, a confidence interval describes the uncertainty around an estimated effect or rate under a statistical model and repeated-sampling framework. A wider interval indicates less precision, while a narrower interval indicates more precision, subject to the model’s assumptions. An interval does not remove selection bias or turn a non-randomized comparison into a randomized one. No confidence interval for the primary endpoint is reported in the registry record, so the precision of any response estimate cannot be assessed from the recorded information.

What can the design say about treatment effects?

In general, a comparison is most informative when groups are formed in a way that supports a fair counterfactual: what would have happened to comparable participants under another treatment strategy. Randomization can support that comparison by reducing systematic differences at baseline. Here, allocation is non-randomized, the study is listed as single group, and the later options are assigned according to progression and ER/PR status. Those features mean that comparing outcomes across cohorts would mix treatment differences with differences in the participants and their clinical course. The registry explicitly warns that the groups are not a like-for-like control comparison.

The treatment sequence also matters for counting and analysis. The registry describes participants who progressed on trastuzumab plus pertuzumab alone as eligible for later treatment. It describes the primary population as moving from Cohort 1 to Cohort 2 Arm B. Therefore, cohort-level counts may reflect treatment stages rather than distinct, mutually exclusive participant sets. As a general statistical matter, repeated observations or overlapping cohort membership must be handled with a defined analysis method; treating linked observations as independent can understate uncertainty. The registry record does not report a method for handling cohort transitions.

What do the planning assumptions mean?

The registry’s sample-size assumptions describe a planning illustration based on an observed effect, with a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. The effect to detect is described as a stated fraction of the observed effect. The record says that time-to-event planning uses a total event count, while other planning outputs are expressed as participants per arm. These are planning conventions, not observed outcomes and not evidence of observed power.

In general, a sample-size calculation estimates what study size might be needed to detect a specified effect under stated assumptions. Its result depends on the assumed effect, variability or event rate, allocation, significance level, and analysis method. A planning illustration does not establish that a study was designed with those assumptions, unless the protocol confirms that. The registry does not report a sample-size justification or a detailed protocol-based statistical plan. No numerical planning output is stated in the registry record details, so no required sample size can be inferred from them.

For time-to-event outcomes such as progression-free survival or overall survival, general planning methods often focus on the number of events because information accrues as events occur. The record’s planning note identifies a total-event approach for these outcomes. This does not provide a reported time-to-event analysis, follow-up distribution, hazard estimate, or result. None of those is reported in the registry record.

Why do analysis details matter?

As a general statistical concept, an analysis plan specifies how endpoint observations, missing assessments, participants who stop treatment, and repeated or sequential measurements will be handled. It may also define the effect measure, model, uncertainty interval, and any adjustment for multiple outcomes. Those choices can affect interpretation. The registry lists zero analyses and does not report these details. It is therefore not possible to determine from the record whether any adjusted or model-based analysis was planned or performed.

Over-dispersion is a general issue in count data when variation exceeds what a chosen probability model expects. In that situation, a model that assumes too little variation can produce uncertainty estimates that are too small. This concept does not establish that over-dispersion occurred in this study; the record provides no fitted count model or dispersion estimate. More broadly, a model should only be discussed as an actual trial method when the registry reports it. Here, the available statistical interpretation is constrained to the design classifications, endpoint definitions, and descriptive counts recorded.

10. Multiplicity, Missing Data and Analysis Populations

The registry lists five outcome measures in total: the primary overall response endpoint and secondary outcomes covering progression-free survival, overall survival, treatment-related adverse events, and quality of life via patient-reported outcomes. When a study evaluates multiple outcomes, the chance of at least one apparently unusual result can increase if each is tested separately at a conventional threshold. In general, multiplicity procedures can control or describe that issue, but the appropriate approach depends on the objectives and prespecified testing strategy.

A multiplicity adjustment or testing hierarchy is not reported in the registry record. The record also lists zero analyses, so no inferential results or testing strategy can be reviewed. This absence does not show that no analysis was ever conducted; it means such an analysis is not reported in the registry record.

Missing-data methods and analysis populations are also not reported in the registry record. The primary endpoint’s population is described as participants who started in Cohort 1 and continued in Cohort 2 Arm B due to progressive disease, but the record does not state how participants with unavailable assessments, early discontinuation, or incomplete follow-up were handled. It does not identify an intention-to-treat, per-protocol, or other analysis population.

As a general statistical point, missing outcomes can affect estimates when the likelihood of missingness is related to disease status, treatment, or other participant characteristics. The direction and extent of any effect depend on the missingness pattern and analysis assumptions. Without reported counts of missing assessments and a stated method, the influence of missing data cannot be evaluated. Similarly, the registry’s progression-based movement between cohorts calls for explicit handling of participant transitions, but that handling is not reported.

11. 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 5% reporting threshold.

Most frequent non-serious adverse event terms

The registry lists serious adverse events for Cohort 1: T+P among two participants at risk, with zero affected. For Cohort 2 - Arm A, it lists zero participants at risk and zero affected. For Cohort 2 - Arm B, it lists zero serious adverse events among two participants at risk. These are the counts recorded for the cohorts, not estimates of comparative risk.

For other adverse events, the registry lists two participants affected among two at risk in Cohort 1 and two affected among two at risk in Cohort 2 - Arm B. Cohort 2 - Arm A has zero at risk and zero affected. The record also lists two deaths for Cohort 1 and two for Cohort 2 - Arm B, with none for Cohort 2 - Arm A. These listings do not establish that adverse events or deaths were caused by treatment. The registry’s secondary outcome description refers to treatment-related adverse events assessed by CTCAE v4.0, but the counts alone do not clarify attribution for each event.

The cohort pathway is essential to reading these figures. Participants who progressed on T+P could continue to a later treatment cohort, and the primary endpoint population explicitly follows the path into Arm B. Cohort counts may therefore describe treatment stages involving the same participants rather than independent sets. They should not be added as though each cohort necessarily contained different people. The record does not provide event-level details or a more complete account of overlap.

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

The registry record documents a phase II study of trastuzumab plus pertuzumab, with additional hormonal therapy or chemotherapy described for participants who progressed. It provides the primary endpoint definition, secondary outcomes, and descriptive adverse-event counts. It does not report a numerical primary response result. As a result, the posted record does not establish how many participants met the response definition or how precisely an outcome rate was estimated.

The record also does not support a treatment comparison. The study was non-randomized and single group, and the later treatment choices depended on progression and ER/PR status. The registry itself notes that the arms are not a like-for-like control comparison. Differences between cohort outcomes, if considered, could reflect these participant-selection and disease-course differences rather than the treatment added at the later stage.

The safety counts are descriptive and should not be interpreted as proof of treatment causation. The registry lists zero serious adverse events among the participants at risk in Cohort 1 and Cohort 2 Arm B, and other adverse events affecting all participants listed as at risk in those cohorts. It also lists deaths in those cohorts. The available counts do not provide a basis for attributing events or deaths to treatment, and the sequence means that cohort entries may not represent independent participants.

In general, a small study can be informative for describing feasibility, procedures, and observed events, but estimates from a very limited participant group are imprecise and may not represent broader populations. Here, enrollment was 2. The registry provides no confidence interval or numerical response estimate with which to quantify precision. The record’s status is terminated, but the reason is not reported in the registry record.

The findings that can be stated are consequently narrow: the study had the listed design and treatment pathway, specified a response endpoint and other outcomes, and recorded the stated safety counts. The registry does not provide enough reported outcome or analysis information to draw comparative conclusions about efficacy, quantify treatment effects, or establish causal safety relationships.

13. Why This Trial Matters Statistically

This trial is statistically notable because its treatment pathway and endpoint population are linked to disease progression. Participants began with trastuzumab plus pertuzumab, while the additional options were described for those whose disease progressed. The primary endpoint population specifically follows participants from Cohort 1 into Cohort 2 Arm B. This illustrates why a cohort label cannot automatically be read as a distinct randomized group: treatment stages may be connected, and eligibility for a later stage can select participants with particular disease histories.

The study is also a clear example of the distinction between an endpoint definition and an endpoint result. The registry defines response categories and an assessment schedule, but a definition alone does not say how many participants met the criteria. Without a numerical primary result and its uncertainty, neither the size nor precision of a response estimate can be evaluated.

Its non-randomized, single-group classification matters for causal interpretation. Comparisons across the treatment pathways would be vulnerable to selection differences because later therapy depended on progression and ER/PR status. The registry’s warning that the arms are not like-for-like controls reinforces a general lesson: treatment descriptions do not by themselves create valid comparison groups.

Finally, the recorded safety counts demonstrate why denominators, participant overlap, and attribution matter. Counts from sequential cohorts should not be added as if the cohorts were independent, and an adverse event or death listed in a treatment cohort is not automatically evidence that treatment caused it. Careful statistical reading separates what the registry records from what its design and reporting do not establish.

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.

Enrollment was 2, and the registry does not report a numerical primary response result. This sharply limits what can be learned about the frequency or precision of response from the record. A confidence interval, response proportion, and statistical test result are not reported in the registry record.

The study was non-randomized, unmasked, and single group. There is no randomized control group for separating treatment effects from participant characteristics, disease course, or other influences. The later treatment options were linked to progression and ER/PR status, so cohort membership reflects clinical pathway conditions as well as treatment. The registry explicitly cautions that the arms are not a like-for-like control comparison.

The primary endpoint population is restricted to participants who started in Cohort 1 and continued into Cohort 2 Arm B because of progressive disease. This is not described as the full enrollment population. The record does not explain how movement between cohorts was handled in analysis, whether participants contributed information at multiple stages, or how incomplete assessments were treated.

The study is listed as terminated, but the reason is not reported in the registry record. A sample-size justification, detailed statistical analysis plan, multiplicity method, missing-data method, and named analysis populations are also not reported. Although secondary outcomes are listed, numerical results for them are not included in the registry record information. The safety data are descriptive and do not establish treatment attribution. Together, these reporting and design limitations restrict interpretation to the stated aims, definitions, and counts rather than comparative or causal conclusions.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: 1303GCC: Trastuzmab & Pertuzumab With Hormonal Therapy or Chemotherapy in Women Aged 60 and Over. — NCT02000596.
• Registry record last updated 2022-05-27; status last verified 2022-05.
• Results first posted 2022-05-27.
• 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

The registry describes a phase II, non-randomized, unmasked, single-group study sponsored by University of Maryland, Baltimore. Enrollment was 2, the start date was 2014-01, the primary completion date was 2015-11, and the study status is terminated. The reason for termination is not reported in the registry record.

The treatment pathway began with trastuzumab plus pertuzumab. Participants who progressed were described as receiving additional hormonal therapy if ER/PR positive or eribulin if ER/PR negative. The primary outcome was a response count defined using complete response, partial response, and stable disease, with assessment every two cycles up to 11 months. The primary population was described as participants continuing from Cohort 1 into Cohort 2 Arm B after progression.

The registry lists progression-free survival, overall survival, treatment-related adverse events, and quality of life via patient-reported outcomes as secondary outcomes. It reports descriptive safety counts but no numerical primary response result or analysis results. The groups are not randomized like-for-like controls, and the record does not report a detailed statistical plan, missing-data methods, or multiplicity approach.