A Study of Pertuzumab in Participants With Metastatic Breast Cancer: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for A Study of Pertuzumab in Participants With Metastatic Breast Cancer (NCT02491892), a randomized phase 2 study. The primary outcome is Percentage of Participants Achieving a Best Overall Response of Confirmed Complete Response (CR) or Partial Response (PR).

2. Clinical Question

3. Trial Design

This was a randomized, open-label, phase II, multicenter study with a parallel-group design. The two groups received different pertuzumab dosing regimens. Because the study was unmasked, participants and study personnel were not blinded to the assigned regimen, according to the registry record. Random assignment can support a fair comparison between groups, while the open-label design is relevant when interpreting outcomes that could be affected by knowledge of treatment assignment.

The registry record lists enrollment of 79 participants. The brief description says approximately 120 participants would be enrolled, so the reported enrollment and the approximate number in the study description are not the same. The record does not explain this difference. The primary result includes 41 participants in the 420 mg group and 37 in the 1050 mg group; the number analyzed for other endpoints can differ. How participants were allocated, whether any were excluded after randomization, and the reasons for any difference between enrollment and analyzed denominators are not reported in the registry record.

The 420 mg regimen included an 840 mg loading dose followed by 420 mg every 3 weeks. The 1050 mg regimen had no loading dose and used 1050 mg every 3 weeks. Both regimens continued until progression or unacceptable toxicity. The registry lists the study as completed, with a start date of 2003-02 and primary completion in 2005-04.

The primary assessment was the percentage achieving a confirmed complete or partial response. The registry also lists secondary outcomes concerning response, progression, treatment failure, and death. The posted material does not state the protocol’s sample-size justification, the randomization method, or a prespecified statistical analysis plan. Those design details 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.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: ITT Population.

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: Intent-to-Treat (ITT) Population: All randomized participants who received at least one dose of pertuzumab.

6. Primary Endpoint

The registry lists the primary outcome as Percentage of Participants Achieving a Best Overall Response of Confirmed Complete Response (CR) or Partial Response (PR), measured over Up to approximately 1 year (at Baseline; every 6 weeks for the first 8 cycles, then every 12 weeks until progression or death; and up to 4 weeks after initial response).

The primary endpoint is the percentage of participants whose best overall tumor response was a confirmed complete response (CR) or partial response (PR). It combines two response categories: confirmed CR required disappearance of all target lesions, while confirmed PR required at least at 30 percent (%) decrease in the sum of the longest diameters of target lesions. A response had to be confirmed at a follow-up assessment completed within 4 weeks of the first documented response. Tumor response was assessed using RECIST.

This endpoint is used to describe how many participants met the specified tumor-response criteria during the assessment period. It is a binary outcome at the participant level: each participant either met the combined CR-or-PR definition or did not. The reported percentage is based on the number meeting the criteria divided by the number analyzed. It does not measure how long a response lasted, whether disease remained stable, or time to progression; those are distinct outcomes listed separately in the registry.

The endpoint timeframe is up to approximately 1 year, with assessments at baseline, every 6 weeks for the first 8 cycles, then every 12 weeks until progression or death, and up to 4 weeks after initial response. A confirmed response definition helps distinguish documented responses from changes observed only once. Even so, the endpoint is a summary of response frequency and does not, on its own, describe the full course of disease or establish the comparative effect of the two regimens.

7. Results Posted in the Registry

• Pertuzumab 1050 mg: 0.0% (0/37) versus 4.9% (2/41) on control; risk difference -4.9 percentage points (95% CI -11.5 to 1.7); unadjusted two-proportion z-test p = 0.174.

8. Secondary Efficacy Endpoints

The registry also posts results for secondary outcomes. For each outcome below, the endpoint type, the test applied to the posted summary statistics, the result and its interpretation are given in turn. Secondary endpoints are usually not adjusted for multiple testing, so they support rather than confirm the primary finding.

Number of Participants Who Experienced PD or Death

• Endpoint type: Binary: the number of participants with the event, compared as proportions.
• Test: Unadjusted two-proportion z-test, with a Wald 95% confidence interval for the risk difference.
• Result:
  • Pertuzumab 1050 mg: 97.3% (36/37) versus 92.7% (38/41) on control; risk difference 4.6 percentage points (95% CI -4.9 to 14.1), risk ratio 1.05 (0.95–1.16); unadjusted two-proportion z-test p = 0.356.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between Pertuzumab 1050 mg and the control. The interval gives the range of effects that remain compatible with the data.

Percentage of Participants Who Died

• Endpoint type: Binary: the percentage of participants with the event (counts rebuilt from the posted percentages and group sizes).
• Test: Unadjusted two-proportion z-test, with a Wald 95% confidence interval for the risk difference.
• Result:
  • Pertuzumab 1050 mg: 32.4% (12/37) versus 46.3% (19/41) on control; risk difference -13.9 percentage points (95% CI -35.4 to 7.6), risk ratio 0.70 (0.40–1.24); unadjusted two-proportion z-test p = 0.210.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between Pertuzumab 1050 mg and the control. The interval gives the range of effects that remain compatible with the data.

Percentage of Participants Achieving a Best Overall Response of SD

• Endpoint type: Binary: the percentage of participants with the event (counts rebuilt from the posted percentages and group sizes).
• Test: Unadjusted two-proportion z-test, with a Wald 95% confidence interval for the risk difference.
• Result:
  • Pertuzumab 1050 mg: 37.8% (14/37) versus 43.9% (18/41) on control; risk difference -6.1 percentage points (95% CI -27.9 to 15.7), risk ratio 0.86 (0.50–1.48); unadjusted two-proportion z-test p = 0.587.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between Pertuzumab 1050 mg and the control. The interval gives the range of effects that remain compatible with the data.

The registry lists secondary outcomes covering tumor response, progression, death, and treatment failure. Across these measures, the general pattern is that several outcomes are common, while confirmed tumor responses are uncommon in the posted primary result. Outcomes such as stable disease and progression or death describe different aspects of participants’ courses than the primary CR-or-PR endpoint. They should not be treated as interchangeable evidence of response.

The secondary results can give context to the primary endpoint, but they do not resolve its uncertainty. The registry lists 19 secondary outcomes and no reported analyses for the posted secondary endpoints. The displayed comparisons are unadjusted recalculations from summary statistics. They are therefore useful as descriptive comparisons, but should not be treated as confirmatory evidence or as substitutes for a prespecified primary analysis.

General statistical explanation: examining multiple outcomes creates multiple opportunities to observe a result that appears notable by chance. A multiplicity adjustment or a prespecified hierarchy can help control how confirmatory claims are made across many tests. The registry record does not report such a strategy. Without that context, isolated secondary p-values deserve less weight than a prespecified primary result, particularly when endpoints differ in definition, follow-up period, or clinical meaning.

Secondary outcomes also vary in what they capture. A proportion experiencing progression or death, for example, is not the same measure as time to progression or duration of response. Time-to-event outcomes account for when events occur and may also involve censoring; a simple event count does not convey that timing. The posted summaries should be read according to each endpoint’s stated definition and timeframe, rather than combined into a single overall conclusion.

These secondary data can help describe the range of outcomes recorded in the study, but the absence of reported analyses and multiplicity information limits inferential interpretation. They do not make the primary response estimate more precise, and they do not establish that the dosing regimens differ or are equivalent.

Secondary outcomes registered for this trial, for reference (only those above were recalculated):

• Time to Response Among Participants Achieving a Best Overall Response of Confirmed CR or PR
• Duration of Response Among Participants Achieving a Best Overall Response of Confirmed CR or PR
• Percentage of Participants Achieving a Best Overall Response of Confirmed CR
• Duration of Response Among Participants Achieving a Best Overall Response of Confirmed CR
• Number of Participants Who Experienced PD or Death
• Time to Progression
• Number of Participants Who Experienced PD or Withdrew From the Study Early
• Time to Treatment Failure

9. Statistical Interpretation

10. Statistical Methods Explained

The primary outcome is binary at the participant level: a participant either had a best overall response of confirmed CR or PR, or did not. The registry reports each group’s percentage and the analyzed denominator. For the comparison, the posted effect measure is a risk difference, calculated as the response proportion in the 1050 mg group minus the response proportion in the 420 mg group. The estimate is -0.049. A negative value indicates a lower observed response proportion in the 1050 mg group under that subtraction order.

What does the confidence interval describe?

General statistical explanation: a confidence interval describes uncertainty around an estimated effect under the assumptions of the method used. It is not a range that guarantees the true effect lies within its endpoints, and it does not give the probability that a particular effect is true. For the primary comparison, the 95% interval runs from -0.115 to 0.017. Because the interval includes zero, the data do not distinguish the observed difference clearly from no difference at the conventional level. Its width also signals substantial uncertainty about the size and direction of the difference.

How should the p-value be read?

The unadjusted p-value for the primary comparison is 0.174. General statistical explanation: a p-value describes how unusual data at least as incompatible with a specified null hypothesis would be if that null hypothesis and the analysis assumptions were correct. It is not the probability that the null hypothesis is true, nor is it a measure of clinical importance. A p-value above 0.05 does not establish equivalence or prove the absence of an effect. In this study, the small number of responses and the broad interval make the size of any difference uncertain.

What does “unadjusted” mean?

The posted p-value is an unadjusted recalculation from the group summary statistics. No reported analysis is listed for the primary endpoint. An unadjusted comparison does not account for a family of multiple tests. General statistical explanation: when many outcomes or comparisons are examined, the chance of at least one apparently notable result can increase if each is judged on its own. The registry does not report a multiplicity strategy, so the primary p-value should not be interpreted as adjusted for other outcomes or analyses.

Why can sparse responses matter?

General statistical explanation: with few outcome events, a change in the status of a small number of participants can move the estimated group proportions noticeably. Sparse data also tend to yield less precise estimates. Here, the primary result includes 2 responses in the 420 mg group and none in the 1050 mg group. The confidence interval makes the uncertainty visible; the point estimate alone would not.

How should the planning illustrations be understood?

The posted sample-size illustrations use the observed effect as their starting point, with scenarios for detecting 100% of the observed effect, 75% of the observed effect, and 50% of the observed effect. Their assumptions are a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. These are planning illustrations, not the trial’s original design justification and not observed power. The protocol’s own sample-size rationale is not reported in the registry record. General statistical explanation: planning estimates depend on the effect considered worth detecting, the variability of the outcome, and the design assumptions. Using an effect estimated from a small study can produce unstable planning figures, so the illustrations should not be treated as firm requirements for a future study.

The record lists no reported analyses for the posted secondary outcomes. Their displayed comparison statistics are unadjusted recalculations from summary data. General statistical explanation: a recalculated test may not match a prespecified trial analysis if that analysis used different assumptions, a different population, covariate adjustment, or another method. Those details are not reported in the registry record, so the recalculations are best understood as simple comparisons of the posted summaries.

11. Confidence Intervals and Precision

The primary estimate is a risk difference of -0.049 for the 1050 mg regimen compared with the 420 mg regimen. Its 95% confidence interval is -0.115 to 0.017. The interval crosses zero, so the data are compatible with no difference in response proportions. It also extends in both directions from zero, leaving uncertainty about whether the underlying difference favors either regimen. The point estimate alone does not convey this uncertainty.

The confidence interval is relatively broad in relation to the small number of observed responses: there were 2 responses among 41 participants in the 420 mg group and 0 among 37 participants in the 1050 mg group. General statistical explanation: intervals tend to be wider when information is limited, and sparse binary outcomes can make estimates sensitive to a few observations. A wide interval does not mean that all values within it are equally plausible, but it does caution against treating the point estimate as precise.

The unadjusted p-value is 0.174. The p-value and interval address related questions but are not interchangeable: the interval shows a range of effects compatible with the estimate under its method, while the p-value measures the compatibility of the data with a null hypothesis under specified assumptions. Neither establishes that the regimens are equivalent. The registry does not report a prespecified equivalence or non-inferiority margin.

The primary endpoint is based on an ITT population, but the registry record does not explain missing outcome handling or the relationship between the analyzed denominators and all enrolled participants. That missing information is relevant to precision and potential bias. No adjusted primary analysis is listed, and the exact statistical method used for the registry comparison is not reported. The displayed estimate is an unadjusted recalculation from the posted summary statistics.

12. Multiplicity, Missing Data and Analysis Populations

The registry identifies the primary endpoint and lists secondary outcomes, but it does not report a statistical analysis plan specifying how multiple outcomes or comparisons were handled. No reported analyses are listed for the primary or secondary results in the posted material. The comparison statistics are unadjusted recalculations from the summary data. Consequently, the registry record does not establish which secondary tests, if any, were prespecified as confirmatory or whether any multiplicity adjustment was planned.

General statistical explanation: multiplicity matters when several hypotheses are tested. If each test is considered independently, the chance of obtaining at least one small p-value by chance can increase as the number of tests grows. A prespecified testing hierarchy, an adjustment procedure, or an explicitly exploratory interpretation can address this issue. The record does not report which approach, if any, was used. Secondary comparisons should therefore be interpreted cautiously and should not be elevated to confirmatory findings solely because an unadjusted p-value is available.

The primary population is identified as ITT. The primary denominators are 41 and 37, while enrollment is reported as 79. The registry does not describe the number randomized to each group, participants excluded from the analysis, the reasons for any exclusions, or whether all randomized participants were included in the ITT analysis. The brief description states that approximately 120 participants would be enrolled, and the record does not explain why the final enrollment was 79.

Missing outcome handling is not reported in the registry record. It is therefore unclear how participants without an evaluable response assessment were treated, whether missingness differed between groups, or whether any sensitivity analysis was performed. General statistical explanation: missing outcome data can affect an estimate if the chance of having an observed result is related to the outcome or differs across groups. The record does not provide enough detail to assess that possibility.

The protocol’s sample-size justification and any interim analyses are not reported in the registry record. The posted planning illustrations are based on observed effects and should not be confused with the trial’s original planning assumptions or with observed power.

13. Safety Results

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

Other (non-serious) adverse events

Participants with at least one non-serious event at or above the registry's 5% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: ejection fraction decreased (4.9%), ascites (2.7%), diarrhoea (2.7%), dysphagia (2.7%), large intestinal obstruction (2.7%).

For serious adverse events, the registry reports 10 of 41 participants in the 420 mg group and 8 of 37 in the 1050 mg group as affected. For other adverse events, it reports 36 of 41 and 37 of 37, respectively. These are participant counts with the stated denominators; they do not, by themselves, describe the severity, duration, recurrence, or timing of each event. The registry does not report deaths in the adverse-event summary.

The listed serious adverse event terms include ejection fraction decreased at 4.9%, and ascites, diarrhoea, dysphagia, large intestinal obstruction, and pleural effusion at 2.7% each. These percentages describe reported terms in the registry summary, not proof that the study drug caused them. The record does not provide enough detail to determine attribution, overlap between events, or how event terms were coded.

General statistical explanation: safety counts are descriptive, and estimates based on small groups can be imprecise. A difference in counts is not automatically evidence of a causal difference between regimens. Interpretation also depends on exposure duration, how events were collected, and whether participants could experience more than one event. Those details are not reported in the registry record. The figures should therefore be read as reported safety observations, not as a complete comparative safety analysis.

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

The primary result describes the proportion of participants in each group who achieved a confirmed CR or PR during the specified follow-up. There were 2 such participants among 41 in the 420 mg group and none among 37 in the 1050 mg group. The risk difference estimate was -0.049, with a 95% confidence interval from -0.115 to 0.017 and an unadjusted p-value of 0.174. These data show a low observed response frequency and substantial uncertainty about the comparative difference.

The result does not establish that the 420 mg regimen is better, or that the 1050 mg regimen is worse. The interval includes zero and allows effects in either direction. It also does not establish equivalence: demonstrating equivalence requires a prespecified margin and an analysis designed for that purpose, neither of which is reported in the registry record.

The study compared two dosing regimens of pertuzumab, not pertuzumab with no treatment or with another drug. The result therefore cannot estimate the effect of pertuzumab versus no pertuzumab. It also does not answer whether either regimen changes survival, duration of response, quality of life, or other outcomes. Such conclusions would require relevant outcome data and an appropriate analysis.

The primary endpoint is a response measure based on RECIST criteria. It captures confirmed tumor shrinkage meeting the stated definitions, but it does not capture every potential clinical outcome. Stable disease is reported separately, as are progression, death, and time-based outcomes. Those measures should be interpreted on their own terms rather than used to redefine the primary endpoint.

Finally, the registry does not report details about missing data, the sample-size rationale, or a multiplicity plan. The posted comparisons are unadjusted recalculations. These limitations, alongside the small number of primary responses, mean the estimates are best read as uncertain descriptive evidence rather than a definitive basis for a dose-comparison claim.

15. Why This Trial Matters Statistically

Statistically, this study illustrates the difference between an observed contrast and a precise conclusion. The primary response proportions differ in the posted data, but there are few responses and the confidence interval spans zero. Reporting the point estimate without its interval would obscure how much uncertainty remains. The interval is central to understanding what the study can and cannot distinguish.

The parallel randomized design offers a direct comparison between two dosing regimens of the same drug. At the same time, the open-label design and the lack of reported detail on randomization and missing outcomes limit how fully the comparison can be evaluated from the registry record. The ITT population is named, but the record does not explain its construction or how unevaluable responses were handled.

The study also highlights the importance of separating a primary endpoint from a broader set of secondary outcomes. The registry lists many outcomes, but no reported analyses or multiplicity strategy. Unadjusted secondary comparisons can be useful descriptively, yet they carry less confirmatory weight when the testing framework is not documented. Similarly, sample-size illustrations based on observed effects are not evidence of the trial’s original planning rationale and are not observed power.

Finally, the enrollment count differs from the approximate enrollment described in the study summary, and the registry does not explain the difference. This is a reminder that trial registration records can contain incomplete or differently framed details. Careful interpretation depends on distinguishing documented results from unanswered design and analysis questions.

16. 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.
• Participant counts were reconstructed from posted percentages and arm sizes, so small rounding differences are possible.

The primary endpoint has few observed responses: 2 in the 420 mg group and 0 in the 1050 mg group. This limits precision and makes the comparative estimate sensitive to a small number of outcomes. The confidence interval is broad and includes zero, so the data do not clearly determine the direction or size of the difference.

The registry reports enrollment of 79, while the study description says approximately 120 participants would be enrolled. The reason for this difference is not reported in the registry record. The primary endpoint denominators are 41 and 37, and the record does not explain their relationship to the full enrolled or randomized population, despite identifying the analysis population as ITT.

The study was open-label. The primary endpoint uses defined response criteria, but the registry does not report whether response assessment was independently reviewed or blinded. Such assessment details are not reported in the registry record. Missing response data, exclusions, and sensitivity analyses are also not described.

No statistical analysis plan, sample-size justification, or multiplicity strategy is reported. The posted p-value and effect estimate are unadjusted recalculations from summary statistics, and no reported analysis is listed. The registry record also does not report an equivalence or non-inferiority margin, so the results cannot support a claim that the regimens are equivalent.

Finally, the study compared two pertuzumab doses without a no-treatment or active comparator. Its primary result is limited to confirmed response frequency and does not by itself establish effects on survival, duration of response, or other outcomes. These limitations are specific to the design and information available in the registry record.

17. Related Tutorials

18. Related Statistical Calculators

19. Sources

• ClinicalTrials.gov: A Study of Pertuzumab in Participants With Metastatic Breast Cancer — NCT02491892.
• Registry record last updated 2015-08-25; status last verified 2015-08.
• Results first posted 2015-08-25.
• 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.

20. Record Summary

The registry describes a completed, randomized, open-label, multicenter phase II study of pertuzumab in participants with metastatic breast cancer and low HER2 expression. It compared 420 mg every 3 weeks after an 840 mg loading dose with 1050 mg every 3 weeks without a loading dose. Enrollment was 79; the primary endpoint was assessed in an ITT population.

The primary endpoint was the percentage with a best overall response of confirmed CR or PR by RECIST. The reported proportions were 4.9% for 420 mg and 0.0% for 1050 mg. The risk difference was -0.049, with a 95% confidence interval from -0.115 to 0.017 and an unadjusted p-value of 0.174. The estimate is uncertain and does not establish a difference or equivalence between regimens.

The registry lists secondary outcomes and safety counts, but does not report analyses, the sample-size justification, handling of missing outcome data, or a multiplicity strategy. Those omissions limit inferential interpretation of the posted comparisons.