Pertuzumab, Trastuzumab, and Paclitaxel Albumin-Stabilized Nanoparticle Formulation in Treating Patients With HER2-Positive Advanced Breast Cancer: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Pertuzumab, Trastuzumab, and Paclitaxel Albumin-Stabilized Nanoparticle Formulation in Treating Patients With HER2-Positive Advanced Breast Cancer (NCT01730833), a na phase 2 study. The primary outcome is Progression Free Survival (MBC Cohort).

2. Clinical Question

3. Trial Design

This was a phase II, prospective, open-label, single-group study sponsored by City of Hope Medical Center. The registry lists an enrollment of 63 and records the study as completed. Its recorded start date is 2013-07-25 and its primary completion date is 2021-01-12. Allocation is listed as not applicable, and masking as none.

The treatment regimen combined pertuzumab, trastuzumab, and paclitaxel albumin-stabilized nanoparticle formulation, also called nab-paclitaxel. Pertuzumab was administered intravenously on day 1. Trastuzumab and nab-paclitaxel were administered intravenously on days 1, 8, and 15. Courses were scheduled to repeat every 21 days unless disease progression or unacceptable toxicity occurred. Laboratory biomarker analysis was also listed as an intervention.

The registry describes a cohort of patients with stage IV HER2-overexpressing metastatic breast cancer and a cohort with HER2-positive locally advanced breast cancer. The primary progression-free survival outcome was specified for the metastatic cohort only. The record explicitly says that progression-free survival was not performed for the locally advanced cohort, where patients received neoadjuvant treatment; disease-free survival is identified as a more relevant analysis for that cohort.

Because there was no randomized control group, the study design does not support a randomized comparison of the combination against another treatment. The cohorts also differ by disease setting, so a comparison between them would not serve as a direct treatment contrast. The registry record does not report a sample-size justification or further details of the protocol’s statistical planning.

4. Participant Flow and Accounting

The registry reports how participants moved through each stage of the study. All counts below are exactly as posted; missing counts are not inferred from other stages.

Overall Study

Analysis population for the primary outcome, as defined in the registry: PFS was not performed on the LABC cohort (neoadjuvant patients). A more relevant analysis, Disease-free survival is present elsewhere in these results.

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 Progression Free Survival (MBC Cohort), measured over assessed up to 5 years.

The primary endpoint was progression-free survival for the metastatic breast cancer cohort, measured in months and assessed up to 5 years. It was defined as the time from initial treatment until disease progression or death. Progression followed RECIST v1.1: a 20% increase in the sum of the longest diameter of target lesions, a measurable increase in a non-target lesion, or the appearance of new lesions.

Progression-free survival is a time-to-event outcome. It incorporates both whether an event occurs and the time until that event, rather than recording only a response at a particular visit. In general, this type of endpoint can describe the period during which a patient remains alive without recorded progression. Death is included as an event in the registry definition, alongside disease progression.

The record says the estimate was to be made with the product-limit method of Kaplan and Meier. It identifies the median and a 95% confidence interval as the endpoint summary, but the actual median and interval are not reported in the registry record. The endpoint is restricted to the metastatic cohort. The record says it was not performed for the locally advanced cohort and points instead to disease-free survival as more relevant there.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

How is progression-free survival summarized?

The registry specifies the product-limit method of Kaplan and Meier for estimating progression-free survival. In general, this method uses the observed event times to estimate the probability of remaining free of the defined event over time. It can account for participants whose event time is not observed during follow-up by using the information available up to their last known observation. Such observations are commonly called censored; the registry’s endpoint description does not give further details about censoring rules or follow-up procedures.

The endpoint event is defined as progression or death, with progression assessed using RECIST v1.1 criteria. The median is a summary of the estimated time-to-event distribution: it marks the time at which the estimated progression-free proportion reaches the halfway point. A median is not an average, and it does not describe every patient’s course. The registry identifies the median as the reported parameter but does not report its value.

What does the confidence interval communicate?

A confidence interval describes the uncertainty around an estimate under the statistical method used. In general, a wider interval indicates less precision than a narrower interval. The registry specifies a 95% confidence interval for the median progression-free survival, but the interval endpoints are not reported in the registry record. Therefore, the precision of the median cannot be assessed from the recorded endpoint definition.

A confidence interval is not a guarantee that the true value lies within a particular calculated interval, nor does it substitute for the study design. Even a precise estimate from a single-group study would not create a randomized treatment contrast. Precision and causal comparison answer different questions: the former concerns uncertainty in an estimate, while the latter depends on the design and analysis supporting a comparison.

Why does the single-group design matter?

This study is identified as single-group, with allocation listed as not applicable and masking as none. These design details mean there is no randomized control group against which to estimate a treatment difference. Outcomes within the treated cohort can describe what was recorded among its participants, but they do not alone show what would have happened to comparable patients under another treatment. Differences between the metastatic and locally advanced cohorts would also be difficult to interpret as treatment differences because the cohorts have distinct disease settings and the primary endpoint was not performed for the locally advanced cohort.

The registry’s statistical-method note says that only sponsor-reported hazard ratios are used for time-to-event outcomes. No sponsor-reported hazard ratio is included in the record. A hazard ratio, in general, compares event rates over time between groups; it is not the same as a difference between medians. Here, there is no registered randomized group comparison and no reported hazard ratio to interpret.

How should planning calculations be understood?

The record describes sample-size calculations as planning illustrations based on the observed effect, not as the trial’s own design. It states assumptions of a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation, with the effect to detect expressed as a fraction of the observed effect. For time-to-event outcomes, the stated planning quantity is the total number of events; for other outcomes, it is participants per arm.

Such calculations are hypothetical design aids. They ask what sample size could be needed under specified assumptions to detect a chosen effect. They do not measure the probability that this completed study detected an effect, and they are not observed power. Since the actual primary estimate is not reported in the registry record, no effect size or planning result should be inferred from the endpoint description. The registry does not report the trial’s own sample-size justification.

Over-dispersion is a general statistical concern when outcome variability is greater than a model assumes; if ignored, uncertainty can be understated. The registry does not specify a model involving over-dispersion for this primary endpoint, so that issue cannot be attributed to the trial’s analysis. The stated Kaplan-Meier method is a nonparametric time-to-event estimator, and the record does not describe additional model-based adjustment.

What can be inferred from the outcome listing?

The registry lists four outcome measures and zero analyses. It names overall response in the metastatic cohort and five-year overall survival as secondary outcomes, but does not report their numerical estimates in the record. The number of listed outcomes is not evidence that all were measured, analyzed, or fully reported. The record also does not specify a hierarchy among secondary outcomes, an adjustment for multiple comparisons, or the statistical tests used for those outcomes. Accordingly, the posted information supports a description of what was planned or listed, rather than a full evaluation of the statistical analysis.

10. Multiplicity, Missing Data and Analysis Populations

The registry lists four outcome measures and zero analyses. It names overall response in the metastatic breast cancer cohort and five-year overall survival as secondary outcomes, while progression-free survival is identified as the primary endpoint. The record does not identify the other outcome measures in the information available, nor does it provide numerical results for the named outcomes.

When a study assesses multiple outcomes or makes repeated statistical comparisons, the chance of a false-positive finding can increase. Statistical plans may address this through prespecified outcome hierarchies or multiplicity adjustments. The registry record does not report whether any such approach was planned or used, so it is not possible to determine how multiplicity was handled. This absence should not be interpreted as evidence that an adjustment was or was not applied outside the registry information.

The record does not report how missing outcome data were handled, whether participants were censored at particular times, or which analysis populations were used. It also does not describe an intention-to-treat population, a per-protocol population, or rules for excluding observations. Those details matter because time-to-event estimates depend on event ascertainment and follow-up, while response outcomes can depend on how unevaluable cases are treated.

The primary endpoint estimate and its 95% confidence interval are not reported in the registry record. These reporting gaps limit assessment of both the result and its precision. No assumption about missingness, analysis population, or multiplicity method can be made from the outcome definitions alone.

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 0% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: thromboembolic event (11.1%), blurred vision (5.6%), catheter related infection (5.6%), dyspnea (4.4%), atrial fibrillation (2.2%).

The adverse-event record separates a cohort of stage IV HER2-overexpressing metastatic breast cancer patients from a cohort of HER2-positive locally advanced breast cancer patients. For serious adverse events, the record lists 3 affected among 18 at risk in the metastatic cohort and 4 affected among 45 at risk in the locally advanced cohort. For other adverse events, it lists 18 affected among 18 at risk and 45 affected among 45 at risk, respectively. The listed death counts are 8 and 2, respectively.

These are descriptive registry counts, not estimates of treatment-attributable risk. The record does not provide a comparator group, a detailed event ascertainment period, or an explanation of how the counts relate to repeated events or individual participants. Deaths are listed as counts, but their relationship to treatment, progression, or a specific follow-up period is not reported in the registry record.

The registry also lists thromboembolic event at 11.1%, blurred vision at 5.6%, catheter related infection at 5.6%, dyspnea at 4.4%, atrial fibrillation at 2.2%, and cardiac disorders - Other, specify at 2.2% among the top serious-event terms. The denominator and method behind these percentages are not reported in the registry record. The terms and percentages should therefore be read as registry-reported safety summaries, not as comparative rates.

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

The record establishes that a phase II open-label single-group study evaluated a combination of pertuzumab, trastuzumab, and nab-paclitaxel in HER2-positive advanced breast cancer. It identifies a primary progression-free survival endpoint for the metastatic cohort and describes how progression was defined. These details clarify the clinical question the study was designed to address.

The registry record does not report the primary endpoint estimate or its 95% confidence interval. It therefore does not establish the observed median progression-free survival in the metastatic cohort, nor does it show how precisely that median was estimated. Named secondary outcomes include overall response in the metastatic cohort and five-year overall survival, but their numerical results are also not reported in the record.

The single-group design means the study does not provide a randomized treatment comparison. Even if an outcome estimate were available, an outcome observed during treatment would not, by itself, establish the difference that would have occurred under another treatment. The record also does not report an analysis establishing a causal effect. Cohort differences should not be treated as a control comparison, particularly because the locally advanced cohort had a different clinical setting and did not have a progression-free survival analysis.

The safety counts and serious-event terms describe what the registry records, but do not establish that the treatment caused a particular event or quantify comparative safety. The record does not give the event denominator for the listed percentages or a comparator group. The appropriate reading is therefore descriptive and limited to the recorded counts and terms.

Overall, the registry documents the design, regimen, endpoint definitions, and selected safety summaries. It does not report the statistical results needed to judge the primary endpoint’s magnitude or precision. Absence of a reported estimate is not evidence of a favorable or unfavorable result; it is a limit on what can be concluded from the registry record.

13. Why This Trial Matters Statistically

This trial is statistically informative as an example of how design determines the questions an outcome can answer. Its primary endpoint is a time-to-event measure, and the registry identifies the Kaplan-Meier product-limit method and a median with a 95% confidence interval. Those choices describe a way to summarize event timing and its uncertainty. The endpoint definition also specifies the event criteria and the population to which the analysis applies.

At the same time, the single-group, open-label design sharply limits comparative interpretation. A treatment cohort can be described, but without a randomized control group there is no like-for-like randomized estimate of a treatment difference. The existence of separate metastatic and locally advanced cohorts does not change that point: they represent distinct disease settings, and progression-free survival was not performed for the locally advanced cohort.

The registry’s outcome listing highlights another practical issue in trial interpretation: a planned or named outcome is not equivalent to a reported result. The record lists four outcome measures and zero analyses, while the numerical primary estimate and confidence interval are not reported. Thus, readers can identify the statistical target but cannot assess its magnitude or precision from this record.

The safety information likewise demonstrates why counts need context. The registry presents cohort-specific affected and at-risk counts and percentages for selected serious-event terms, but lacks a comparator and does not report the percentage denominator or detailed ascertainment information. Those figures should not be mistaken for causal comparisons.

Statistical interpretation depends on both methods and reporting. This record makes the endpoint framework visible, while leaving important outcome estimates, missing-data procedures, analysis populations, and multiplicity methods unreported. Recognizing that boundary is central to a careful reading of clinical trial evidence.

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 central limitation for interpreting efficacy is that the registry record does not report the primary progression-free survival median or its 95% confidence interval. It also does not report a sponsor hazard ratio or numerical results for the named secondary outcomes. The endpoint definition and assessment period cannot substitute for those estimates.

The single-group design has no randomized control group, so it cannot produce a randomized treatment contrast. The open-label design is recorded, but the registry does not describe any procedures intended to address possible assessment or reporting influences. The metastatic and locally advanced cohorts differ in disease setting; the primary progression-free survival analysis was not performed for the locally advanced cohort.

Important analysis details are not reported in the registry record. These include handling of missing data and censoring, analysis populations, multiplicity procedures, the statistical tests used for secondary outcomes, and the trial’s sample-size justification. The record lists four outcome measures and zero analyses, so the relationship between listed outcomes and analyzed results is not clear from the registry information.

The safety summaries are limited by the absence of a control group and by missing context about event ascertainment, follow-up periods, and the denominators underlying the listed serious-event percentages. Death counts are reported without a stated timeframe or attribution. Consequently, the listed safety figures are descriptive and cannot establish comparative or treatment-attributable risk.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Pertuzumab, Trastuzumab, and Paclitaxel Albumin-Stabilized Nanoparticle Formulation in Treating Patients With HER2-Positive Advanced Breast Cancer — NCT01730833.
• Registry record last updated 2026-11-03; status last verified 2026-10.
• Results first posted 2023-06-28.
• 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

The registry describes a completed phase II, prospective, open-label, single-group study sponsored by City of Hope Medical Center. It lists an enrollment of 63, a start date of 2013-07-25, and a primary completion date of 2021-01-12. The intervention combined pertuzumab, trastuzumab, and nab-paclitaxel.

The primary outcome was median progression-free survival for the metastatic breast cancer cohort, assessed up to 5 years using the Kaplan-Meier product-limit method, with a 95% confidence interval specified. Progression-free survival was not performed for the locally advanced cohort. Although the registry lists four outcome measures, it records zero analyses, and the primary estimate and interval are not reported in the registry record.

Safety information includes cohort-specific serious and other adverse-event counts, death counts, and selected serious-event terms with percentages. The record does not establish a randomized treatment comparison, and key details about analysis populations, missing data, multiplicity, and safety denominators are not reported.