Study of Efficacy and Safety of Myl1401O + Taxane vs Herceptin©+ Taxane for 1st Line, Met. Br. Ca.: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Study of Efficacy and Safety of Myl1401O + Taxane vs Herceptin©+ Taxane for 1st Line, Met. Br. Ca. (NCT02472964), a randomized phase 3 study. The primary outcome is Primary Endpoint : Compare Best Overall Response Rate (ORR) (According to Response Evaluation Criteria in Solid Tumor [RECIST] 1.1 Criteria) at Week 24 of MYL-1401O Plus Taxane Versus Herceptin® Plus Taxane in the ITT1 Population.

2. Clinical Question

The endpoint is a comparison of tumor response categories assessed through measurements reviewed centrally by blinded reviewers. The registry describes complete response, partial response, stable disease, and progressive disease under RECIST 1.1. In general, an overall response rate concerns the proportion of participants meeting the specified response criteria, rather than a change in a continuous measurement.

The clinical question is framed as a randomized, parallel-group comparison of two trastuzumab regimens with investigator-selected taxane treatment. The registry record names the study as first-line therapy in HER2-positive metastatic breast cancer. It does not report the numerical response results, the between-group estimate, or a confidence interval for the primary endpoint. The direction and precision of any difference in response therefore cannot be assessed from the efficacy results recorded.

3. Trial Design

This was a multicenter, randomized, double-blind, parallel-group Phase III study. The registry lists quadruple masking. That label identifies the recorded masking category, but the registry record does not specify which individual roles were masked or how masking was maintained. The study status is completed, with enrollment recorded as 500.

The groups received either MYL-1401O plus a taxane or Herceptin plus a taxane. The taxane options were paclitaxel and docetaxel, chosen by investigators. The arm descriptions state paclitaxel 80 mg/m2 weekly intravenously or docetaxel 75 mg/m2 intravenously once every three weeks, for 8 cycles, followed by evaluation for the primary endpoint. The descriptions then outline continued treatment for participants meeting specified response or disease-status conditions, but the continuation details are not fully reported in the registry record.

The primary efficacy analysis population is called ITT1 in the record and includes all patients randomized after Amendment 2. This definition matters because it is not simply described as every participant enrolled over the entire study; it is tied to a protocol amendment. The registry does not provide the count in ITT1 or explain in detail how participants randomized before Amendment 2 were handled for efficacy.

The start is recorded as 2012-07, and primary completion as 2016-03. The study is marked completed. Those registration details describe the study timeline and status; they do not establish whether every planned analysis was completed or reported. The record does not report the sample-size justification, the protocol's detailed statistical analysis plan, or an account of interim analyses. The posted enrollment should not be interpreted as evidence of the number included in the primary analysis, since the analysis population count is not reported.

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: The primary efficacy analysis was derived fromITT1 population 230 (MYL-1401O) + 228 (Herceptin)= 458. Safety analysis was derived from the Safety Population 247(MYL-1401O)+246(Herceptin)= 493. Total Randomized population 249(MYL-1401O) +251(Herceptin)= 500.

Part 1 (up to Week 24)

Reasons for not completing this period:

Part 2 (Week 24-week 48)

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: The primary efficacy analysis was conducted in the Intent To Treat population 1 (ITT1) ( all patients randomized after Amendment 2 of the protocol)

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: Bseline Analysis Population Description: The primary efficacy endpoint analysis was conducted in the intention to treat (IIT)population ( only those patients randomized after the second amendment of the protocol)

6. Primary Endpoint

The registry lists the primary outcome as Primary Endpoint : Compare Best Overall Response Rate (ORR) (According to Response Evaluation Criteria in Solid Tumor [RECIST] 1.1 Criteria) at Week 24 of MYL-1401O Plus Taxane Versus Herceptin® Plus Taxane in the ITT1 Population, measured over from time of First treatment to week 24.

The primary endpoint is best overall response rate according to RECIST 1.1 at Week 24, measured from the time of first treatment. Tumor measurements were assessed by centralized blinded reviewers. The endpoint is recorded as a count of participants, and the primary efficacy population is ITT1: all patients randomized after Amendment 2.

RECIST 1.1 classifies response using changes in target and non-target lesions. The registry describes complete response as disappearance of target lesions, with an additional size criterion for pathological lymph nodes; partial response requires a defined decrease in the sum of target-lesion diameters. Stable disease does not meet the criteria for sufficient decrease or increase, while progressive disease includes specified increases or the appearance of new lesions. These criteria make response assessment more standardized than an unstructured clinical judgment.

In general, response rate is useful for describing the proportion of participants who meet response criteria at a prespecified assessment. It is a binary summary derived from response categories, even though the underlying assessments distinguish several outcomes. The registry record does not report the number meeting the endpoint in either arm, the response-rate estimates, or a comparison estimate. It also does not report confidence intervals or a p-value for this endpoint, so the magnitude and precision of the efficacy comparison cannot be evaluated from the recorded results.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The following concepts are general explanations of statistical methods, not claims about methods that this trial used. The registry record identifies a randomized design and a binary response outcome, but does not report a detailed statistical analysis plan or inferential analyses for the primary endpoint.

What does a binary endpoint represent?

A binary endpoint places each participant into one of two analysis states for a defined outcome, such as meeting or not meeting a response definition. The best overall response rate is based on response classifications made under RECIST 1.1. Although the clinical assessments have several categories, a response-rate analysis needs a prespecified rule for which categories count as a response and how participants without an evaluable assessment are handled. The registry gives the endpoint name and RECIST descriptions, but does not provide the primary response counts or explain how unevaluable and missing assessments entered the calculation.

For a randomized two-group study, a rate can be reported for each group, followed by a contrast between the rates. That contrast might be expressed on an absolute or relative scale. Different scales answer different questions, so the scale and its interpretation should be stated explicitly. No primary contrast is reported in the registry record, and no new contrast can be calculated from the posted information.

How should uncertainty be described?

In general, a confidence interval represents uncertainty around an estimate under the assumptions of the statistical method. It is not a guarantee that the true value lies in the interval, and it does not show how much an individual participant's outcome may vary. For a response rate, interval width depends on the amount of information and the observed rate. A confidence interval for a difference between groups would express uncertainty in that difference, rather than uncertainty in either group's rate alone.

Interpretation should focus on both the estimate and its interval, if available. A p-value alone does not show the size of a difference or its precision, and statistical significance is not the same as clinical importance. The registry record does not provide a confidence interval or p-value for the primary endpoint. No inferential conclusion can therefore be recovered from the endpoint description alone.

Why does the analysis population matter?

The record defines ITT1 as all patients randomized after Amendment 2. In general, an intention-to-treat approach preserves the comparison created by randomization by analyzing participants in their assigned groups, subject to the exact population definition and analysis rules. Here, the record gives a specific amended-protocol population definition, but does not report its size, the number of participants analyzed, or how the population was applied in the results. Those details are needed to understand how closely the analysis reflects the randomized comparison.

Missing outcome data can affect a binary endpoint because the response status of participants without an assessment is unknown. Methods may handle missing data in different ways, with different assumptions and consequences. The registry record does not report how missing or unevaluable Week 24 assessments were handled. It would be inappropriate to assume that participants with no recorded assessment were excluded, counted as nonresponders, or addressed by a particular imputation method.

What can a planning illustration tell us?

In general, sample-size planning considers a target effect, a significance level, allocation, and statistical assumptions. A planning illustration based on the observed effect is retrospective: it asks what sample size might be associated with detecting a selected fraction of that effect under stated assumptions. It is not the trial's original sample-size justification, and it is not observed power. The illustration described for this study uses a two-sided significance level of 0.05, equal allocation, and a normal approximation; the effect to detect is defined as a fraction of the observed effect. The registry does not report its own sample-size justification.

Planning calculations depend on assumptions about the effect to detect and the analysis. They do not establish that an effect is important, nor do they replace the actual estimate and its uncertainty. Because no primary efficacy estimate is reported in the registry record, the numerical interpretation of planning rows cannot establish the trial's observed treatment contrast. Sample-size illustrations are planning aids, not observed outcomes.

What does randomization contribute?

Generally, random assignment aims to make treatment groups comparable in expectation with respect to measured and unmeasured characteristics. This supports causal interpretation of a well-conducted comparison, but randomization alone does not guarantee complete follow-up, correct outcome measurement, or unbiased analysis. Blinded central review of tumor measurements is part of the recorded endpoint procedure and may limit some sources of assessment variation. The record does not provide enough detail to assess implementation of allocation, masking, missing-data handling, or the full analysis procedure.

10. Multiplicity, Missing Data and Analysis Populations

The primary endpoint is described as a comparison of best overall response rate at Week 24. The registry record does not report a statistical analysis plan specifying how the primary comparison was tested, whether multiple testing was considered, or whether there were additional confirmatory outcomes. A multiplicity adjustment, if any, is not reported in the registry record. Without such documentation, the error-rate strategy for multiple hypotheses cannot be evaluated.

The endpoint is derived from several response categories, but that fact alone does not establish that multiple separate statistical tests were performed. The record describes complete response, partial response, stable disease, and progressive disease as RECIST classifications; it does not give inferential analyses for each category. It would be inappropriate to infer a testing hierarchy or correction procedure from the endpoint description.

The record defines ITT1 as all patients randomized after Amendment 2. It does not report the size of that population, a participant-flow account, or how many participants had an evaluable Week 24 assessment. The handling of missing, unevaluable, or withdrawn participants is not reported in the registry record. Nor is there information about sensitivity analyses examining the effect of missing outcome data.

These omissions limit reproducibility and interpretation. A reader cannot establish from the registry record how the endpoint was calculated when response assessments were unavailable, whether every eligible randomized participant was included, or how the primary finding would change under alternative assumptions. These are reporting gaps, not evidence that particular methods were or were not used outside the record.

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 5% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: neutropenia (27.5%), leukopenia (4.9%), febrile neutropenia (4.5%), pneumonia (2.4%), diarrhoea (1.6%).

The registry lists serious adverse events for 91 of 246 participants in the Herceptin plus taxane group and 97 of 247 participants in the MYL-1401O plus taxane group. It also lists other adverse events for 232 of 246 and 229 of 247 participants, respectively. These are counts with their recorded denominators; they should not be treated as a comparison adjusted for follow-up time or as evidence of a causal difference.

The listed serious adverse-event terms and percentages are Neutropenia, 27.5%; Leukopenia, 4.9%; Febrile Neutropenia, 4.5%; Pneumonia, 2.4%; Diarrhoea, 1.6%; and Vomiting, 1.2%. The registry record does not specify in this listing whether these term percentages are pooled across groups or reported for one group, so a group-specific interpretation is not warranted.

In general, adverse-event counts depend on definitions, collection periods, and the number of participants monitored. The registry record does not report deaths in these safety groups. The figures are descriptive and do not provide a formal statistical comparison or establish that one regimen has a different safety profile.

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

The registry supports a limited description of the study question and selected safety outcomes. It records a randomized Phase III comparison of MYL-1401O plus a taxane with Herceptin plus a taxane, with best overall response rate at Week 24 as the primary endpoint in ITT1. It also records serious and other adverse-event counts by group and a list of serious adverse-event terms with percentages.

However, the numerical primary efficacy results are not reported in the registry record. There is no response count by group, effect estimate, confidence interval, or p-value for the primary comparison. Therefore, the record does not establish the observed direction or size of the response-rate contrast, nor how precisely that contrast was estimated. This should not be paraphrased as evidence of equivalence, similarity, or absence of an effect.

In general, an endpoint result is most informative when the estimate, uncertainty interval, analysis population, and missing-data handling are all available. The trial's randomized design describes how groups were assigned, but it cannot replace these outcome details. Similarly, the study's completed status and recorded enrollment do not establish the result of the ITT1 analysis.

The safety counts can be read as the number of participants recorded with events among the listed group denominators. They do not on their own measure comparative risk over time, account for potential differences in follow-up, or establish a statistical difference between groups. The serious-event terms cannot be attributed to a particular group from the listing alone. Overall, the registry record allows a description of design and some safety reporting, but not a quantitative interpretation of the primary efficacy comparison.

13. Why This Trial Matters Statistically

Statistically, this trial is an example of why design information and outcome information answer different questions. Randomization, masking, and a parallel-group structure describe how the comparison was organized. The primary endpoint definition describes what was intended to be measured. Neither reveals the observed response-rate contrast without the outcome counts and analysis results.

The study also illustrates the importance of defining the analysis population precisely. ITT1 is tied to randomization after Amendment 2, rather than simply being an unspecified group of all enrolled participants. That definition is meaningful for interpreting the intended randomized comparison, but the record does not provide the population size or participant flow needed to see how it was applied in the analysis.

Endpoint standardization is another statistical feature of interest. Centralized blinded review and RECIST 1.1 provide a stated framework for classifying tumor response. Standardized criteria can improve consistency in measurement, while the resulting response categories still need a clearly reported rule for deriving the primary endpoint and handling unavailable assessments.

Finally, the record demonstrates why estimates and uncertainty matter. Safety counts offer descriptive information, but the absent primary efficacy estimate means the main comparative question cannot be quantified. A completed randomized study is not fully interpretable from design details alone; transparent reporting of results, precision, analysis population, and missing-data procedures is necessary for statistical assessment.

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 principal limitation for interpreting this trial from its registry record is that the primary efficacy results are not reported. Although the endpoint is clearly named, no arm-specific response counts or comparative estimate are available. The record also does not provide a confidence interval or p-value. The primary question therefore cannot be answered quantitatively from the posted efficacy information.

The analysis population is defined as ITT1, but its size and participant flow are not reported. The record does not explain the number with evaluable Week 24 tumor assessments, how missing or unevaluable responses were handled, or whether participants were excluded from the analysis. These omissions restrict assessment of the endpoint's completeness and the application of the population definition.

Additional limitations concern statistical reporting. The protocol's sample-size justification, detailed analysis plan, and any interim-analysis procedures are not reported in the registry record. Multiplicity handling and the use of sensitivity analyses are also not reported. These gaps prevent evaluation of the planned inferential framework, but do not demonstrate that such methods were absent from study conduct.

The safety information is also limited. Serious and other adverse-event counts are reported, but no deaths are listed, and the serious-event term percentages are not linked to a specific group in the term listing. The record does not provide an inferential safety comparison. The post-randomization treatment descriptions are not fully reported, which limits a complete account of treatment exposure and continuation rules.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Study of Efficacy and Safety of Myl1401O + Taxane vs Herceptin©+ Taxane for 1st Line, Met. Br. Ca. — NCT02472964.
• Registry record last updated 2022-02-14; status last verified 2022-02.
• Results first posted 2018-10-30.
• 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 record describes NCT02472964, a completed, multicenter, randomized, double-blind, parallel-group Phase III study sponsored by Mylan Inc. It compared MYL-1401O plus paclitaxel or docetaxel with Herceptin plus paclitaxel or docetaxel as first-line therapy for HER2-positive metastatic breast cancer. Enrollment is recorded as 500.

The primary endpoint was best overall response rate by RECIST 1.1 at Week 24 in ITT1, defined as patients randomized after Amendment 2. Numerical efficacy results and an inferential comparison are not reported in the registry record. Safety listings include serious and other adverse-event counts by group and several serious-event terms with percentages, without group attribution for those term percentages.

The record does not report the sample-size justification, detailed statistical analysis plan, missing-data methods, or multiplicity strategy. Its design and endpoint definitions can be described, but the primary efficacy comparison cannot be quantitatively interpreted from the registry outcomes recorded.