Participant Preference of Subcutaneous (SC) Versus Intravenous (IV) Herceptin (Trastuzumab) in Human Epidermal Growth Factor Receptor (HER) 2-Positive Early Breast Cancer: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Participant Preference of Subcutaneous (SC) Versus Intravenous (IV) Herceptin (Trastuzumab) in Human Epidermal Growth Factor Receptor (HER) 2-Positive Early Breast Cancer (NCT01401166), a randomized phase 2 study. The primary outcome is Percentage of Participants by Preferred Method of Drug Administration.

2. Clinical Question

The study asked which administration method participants preferred after experiencing both subcutaneous (SC) and intravenous (IV) Herceptin. Its focus was preference in HER2-positive early breast cancer, rather than a direct comparison of tumor response or survival as the primary question.

Because participants experienced both methods, the design could elicit a preference after exposure to both rather than relying only on expectations before treatment. That approach makes the endpoint directly relevant to participants’ reported experience, but preference is not the same as an objective measure of treatment efficacy or safety. The registry record does not report the preference percentages, their uncertainty, or a statistical comparison between routes.

3. Trial Design

This was a randomized, open-label, Phase 2 crossover study in HER2-positive early breast cancer. The registry record reports enrollment of 488 and identifies the study model as crossover. Participants were assigned to start with SC Herceptin or IV Herceptin, received that method for Cycles 1 to 4, and then crossed over to the other method for Cycles 5 to 8. Treatment was scheduled every 3 weeks. The crossover period ended at Week 24, when participants were asked about their preferred method.

The SC administration approach differed by cohort. Cohort 1 used an SC single-use injection device; Cohort 2 used a handheld syringe with the vial formulation. Within each cohort, the sequence was SC followed by IV or IV followed by SC. The study was unmasked, so participants and healthcare professionals were not blinded to the administration method. This is relevant for an endpoint based on stated preference, because the method itself is apparent to the person reporting that preference.

The registry description includes a continuation period after the crossover. Participants could receive IV or SC Herceptin every 3 weeks for up to 10 additional cycles, for a total of 18 cycles. The arm descriptions indicate that continuation regimens differed according to assigned cohort and sequence, but portions of those descriptions are incomplete in the registry record. The crossover question and the later continuation treatment should therefore be kept distinct: the primary preference assessment was at the end of the crossover period, not after the full continuation period.

The study was sponsored by Hoffmann-La Roche. The registry lists a start of 2011-10, primary completion of 2013-05, and status as completed. It does not report the randomization procedure, allocation ratio, or details of the planned statistical analysis. It also does not report how the study’s enrollment target was justified.

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: A total of 248 participants were randomized into the study in Cohort 1 (of whom 244 were treated) and 240 participants were randomized into the study in Cohort 2 (of whom 239 were treated). Those participants who did not receive any treatment were not included in the treatment periods of the Participant Flow.

Crossover Treatment 1 (Cycles 1 to 4)

Crossover Treatment 2 (Cycles 5 to 8)

Continuation Treatment (Cycles 9 to 18)

Safety Follow-Up Period

Analysis population for the primary outcome, as defined in the registry: Intent-to-Treat (ITT) Population: All participants who received both IV and SC Herceptin and who completed the trial-specific telephone interview conducted after the end of the crossover period.

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: Safety Population: All participants who received at least one dose of Herceptin.

6. Primary Endpoint

The registry lists the primary outcome as Percentage of Participants by Preferred Method of Drug Administration, measured over Week 24.

The primary endpoint was the percentage of participants by preferred method of drug administration, assessed at Week 24. During a trial-specific telephone interview at the end of the crossover period, each participant was asked which method they preferred overall: IV or SC Herceptin. The endpoint therefore summarizes stated preference after participants had received both methods during the crossover period.

A preference endpoint is useful when the practical experience of receiving treatment is itself important to the study question. General explanation: a percentage gives the share of the analysis population reporting each response category, making the distribution of preferences interpretable in relation to the people interviewed. It does not, on its own, establish that one method is more effective or safer.

The registry defines the primary endpoint population as the Intent-to-Treat (ITT) Population consisting of participants who received both IV and SC Herceptin and completed the telephone interview after the crossover period. Thus, the stated analysis population depends on treatment exposure and interview completion, not simply on initial enrollment. The registry record does not report the percentages preferring IV or SC, the number of participants included in that endpoint analysis, or an uncertainty interval for the percentages. It also does not report a formal statistical comparison between the preference categories.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The endpoint is a response distribution: participants were asked to choose their preferred administration method, and the registry describes reporting the percentage preferring each method. The registry record does not report the underlying response counts or percentages, nor does it state a confidence interval or a hypothesis test for this endpoint. The following statistical concepts are general explanations, not claims about analyses performed in this study.

What does a percentage describe?

General explanation: a percentage expresses how common a response was within a defined group. Its interpretation depends on the group included in the denominator and on how responses were categorized. Here, the registry identifies an endpoint population made up of participants who received both IV and SC Herceptin and completed the post-crossover telephone interview. The actual size of that population and the percentages for the response categories are not reported in the registry record.

When a response has more than two possible categories, the distribution across categories matters. The registry describes the endpoint as preference for IV or SC, while its analysis note says that the primary outcome has several categories or time points and was not reduced to one comparison. The record does not give a single effect estimate or a single comparison to interpret. It would be inappropriate to select one category or construct a contrast without the reported result and analysis details.

What would a confidence interval add?

General explanation: a confidence interval describes the uncertainty around an estimate under the assumptions of the statistical method used. For a preference percentage, it can help distinguish a narrowly estimated proportion from one that is compatible with a wider range of values. The registry record does not report confidence intervals for the preference outcome. Consequently, the precision of any preference estimate cannot be assessed from the information.

Why does the crossover design matter?

General explanation: in a crossover study, participants receive more than one study treatment in sequence. This can make comparisons reflect within-participant experience, but the sequence and period can also matter. A participant’s experience during a later period may be influenced by having received a different treatment earlier, and experiences may change over time. These are general considerations for crossover designs, not evidence that carryover or period effects occurred in this study. The registry record does not report whether such effects were assessed or how the statistical analysis handled sequence and period.

Random assignment to the initial method helps determine which sequence participants begin with, but the record does not describe the randomization procedure or allocation ratio. It also does not report a model or test for the primary preference endpoint. No adjustment for potential differences between sequences should be assumed.

What does open-label status imply?

General explanation: masking can reduce the influence of knowledge about treatment assignment on some measurements. Administration route is apparent to participants and healthcare professionals, and this study had no masking. Because the primary outcome was reported preference, knowledge of the method is part of the setting in which the response was given. The outcome still records participants’ stated views; it does not provide a blinded assessment of an objective clinical event.

What can planning calculations say?

General explanation: a sample-size planning calculation estimates the number of participants needed to detect a prespecified effect under specified assumptions. It is not a report of what the study observed and is not a substitute for the endpoint result. The registry record includes general assumptions for planning illustrations based on an observed effect, but does not report the trial’s own sample-size justification. Any planning illustration should be read as hypothetical, not as observed power and not as evidence that a result was statistically significant.

In general, binary outcomes can also be affected by variation greater than a simple model assumes. Over-dispersion means that observed variability exceeds the model’s expected variability; accounting for it can affect uncertainty estimates. The registry does not identify an over-dispersion analysis for the preference endpoint, and no such method should be attributed to this study. More broadly, the absence of a reported analysis method means that the estimand, model, handling of dependence between repeated treatment periods, and uncertainty calculation cannot be reconstructed from the registry record.

10. Multiplicity, Missing Data and Analysis Populations

The study registered multiple outcomes. The secondary outcomes include healthcare professional satisfaction with administration method, time required for each method, event-free survival events and duration, a 3-Year event-free survival rate, participant agreement or strong agreement on the SC SID satisfaction questionnaire, and anti-Trastuzumab or anti-recombinant human hyaluronidase (rHuPH20) antibodies. The record lists 8 outcome measures and 8 analyses, but does not describe a multiplicity adjustment or a hierarchy for interpreting the outcomes.

General explanation: when a study tests or estimates several outcomes, the chance of at least one apparently noteworthy finding can depend on how many analyses are considered and how they are interpreted. A prespecified hierarchy or adjustment can help address that issue. The registry record does not report whether either approach was planned or used, so no multiplicity procedure should be assumed. The primary preference outcome also was not reduced to one comparison in the posted analysis information, leaving the precise inferential target unclear.

The endpoint population requires receipt of both routes and completion of the telephone interview. The number of participants meeting those criteria is not reported in the registry record. The record does not describe missing-data handling, including how incomplete interviews, unavailable responses, or other missing endpoint information were treated. It also does not state whether any sensitivity analyses assessed the influence of missing outcomes.

The registry does not report an interim analysis plan or whether interim analyses took place. It does not report the full statistical analysis plan, including prespecified models, adjustment variables, or methods for the crossover sequence. These omissions limit assessment of how outcomes were selected, how uncertainty was calculated, and whether the posted analysis followed a prespecified approach.

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: cerebral haemangioma (2.3%), wound infection (0.8%), breast reconstruction (0.5%), knee arthroplasty (0.5%), mammoplasty (0.5%).

The registry lists serious adverse event counts separately for crossover and continuation periods, for Cohort 1 using the SC single-use injection device and Cohort 2 using the SC vial formulation. It also gives the number at risk for each listed group. For example, the entries include 4 serious events among 242 at risk for Cohort 1 SC SID during crossover, and 2 among 241 at risk for Cohort 1 IV during crossover. In Cohort 2, the crossover entries are 0 among 237 at risk for SC vial and 2 among 237 at risk for IV. These are counts as recorded, not a complete adjusted comparison.

The record also lists other adverse event counts, which are distinct from the serious adverse event counts. For instance, Cohort 1 crossover entries list 81 other events among 242 at risk with SC SID and 55 among 241 at risk with IV. The registry gives additional continuation and overall cohort entries. These groups and periods should not be combined by adding counts, because the same participants could contribute information across periods and the record does not specify a method for such a calculation.

Selected serious adverse event terms are listed with percentages, including Cerebral haemangioma at 2.3% and Wound infection at 0.8%. The denominator and derivation for each term percentage are not described in the registry record. Death counts are not reported in the registry record. Differences in group size, exposure period, and cohort mean that raw counts alone do not establish comparative risk or causation.

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

This study’s primary question concerns participants’ stated preference after experience with both SC and IV Herceptin. The registry record explains the interview question and identifies the assessment at Week 24. However, the actual preference percentages are not reported in the registry record. It is therefore not possible to say which method participants preferred more often, how large any difference was, or how precise the observed distribution was.

Even with a reported preference distribution, that result would answer a specific question about reported experience among participants who received both methods and completed the interview. It would not, by itself, show that one route is more effective or safer. The secondary outcomes listed in the registry include event-free survival, healthcare professional views, time to perform the administration methods, questionnaire responses, and antibody outcomes. Their results are not reported in the registry information, so they cannot supply evidence for claims about clinical outcomes.

The randomized crossover structure means participants were assigned to an initial sequence and then crossed to the other administration method. It gives the preference question the context of exposure to both methods, while the open-label design means participants knew which method they received. General explanation: a preference response may capture the participant’s overall experience, but it is not a blinded measurement and should be interpreted as a patient-reported outcome.

The registry’s adverse event counts are descriptive and grouped by cohort, route, and treatment period. Without a reported comparative analysis and detail on the applicable exposure and analytic methods, those counts do not establish that a route caused more or fewer events. Likewise, the registry’s planned sample-size assumptions do not establish the study’s achieved statistical power or replace a reported result.

The appropriate boundary is therefore clear: the record documents a randomized, open-label crossover study designed to assess administration preference and other outcomes, with some safety counts recorded. The primary preference finding and the statistical evidence needed to assess its magnitude and precision are not reported in the registry record.

13. Why This Trial Matters Statistically

Preference studies address an outcome that is different from conventional measures of clinical efficacy. When treatments can be delivered in different ways, participants’ experience of administration can be a meaningful research question in its own right. This study used a direct interview question after participants had received both SC and IV Herceptin, making the intended outcome explicit: which method participants said they preferred.

The crossover design is statistically important because each participant experienced both methods during the initial treatment period. General explanation: within-participant designs can reduce the influence of stable differences between individuals when estimating treatment contrasts. But they also require attention to treatment sequence, period, and possible carryover effects. The registry record does not report how these design features were handled in the analysis, so the design alone does not establish the validity or precision of a comparison.

The study also illustrates why analysis populations matter. The primary endpoint was defined among participants who received both routes and completed a telephone interview, rather than automatically including every enrolled participant. Without the number analyzed and information about incomplete interviews, readers cannot judge the extent to which the endpoint population represents all enrolled participants.

Open-label status is especially relevant because the endpoint is reported preference. Participants knew the method they received, and the response was elicited by interview. That is consistent with measuring stated preference, but the result would need to be interpreted as such rather than as an objective efficacy endpoint. The record’s lack of reported preference percentages prevents even that descriptive interpretation from being made.

Finally, the record makes visible the distinction between a study’s question and its posted results. It describes a clear comparison and several secondary outcomes, but does not report the primary preference result or the analysis details needed to assess uncertainty. This is a useful reminder that a registry entry can establish design and measurement without providing enough outcome information to support an effect estimate.

14. Limitations

• The posted summary statistics are the only data these results rest on; patient-level data, full protocols and statistical analysis plans are not available.
• Recalculated results are simple, unadjusted calculations from posted summaries. They do not replace the sponsor's prespecified analysis.

The main trial-specific limitation for interpretation is that the primary preference result is not reported in the registry record. The percentages preferring IV and SC, the number included in the endpoint analysis, and an uncertainty estimate are all absent. The registry therefore does not permit a quantitative interpretation of the study’s principal question.

The primary endpoint population was restricted to participants who received both administration methods and completed the telephone interview. The registry record does not state how many participants met these conditions or how missing interviews were handled. Since enrollment was 488, that figure should not be treated as the number analyzed for preference.

The study was open label and the outcome was a stated preference elicited in a telephone interview. This is aligned with the study question, but makes the result a report of participant preference in an unmasked setting. The record does not describe interview procedures beyond the question and timing, such as interviewer standardization or handling of responses that did not fit the stated categories.

The crossover design introduces sequence and period considerations. The registry record does not report whether carryover, sequence, or period effects were assessed, nor does it specify the analysis model. It also does not report the randomization procedure or allocation ratio. These details are needed to evaluate how the repeated exposure and treatment order were addressed.

Some arm descriptions are incomplete in the registry record, particularly for the continuation period. The secondary outcome results and a full statistical analysis plan are not reported in the registry information. No interim-analysis details, missing-data strategy, or multiplicity procedure are reported. Together, these omissions constrain evaluation of both the primary endpoint and the safety entries.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Participant Preference of Subcutaneous (SC) Versus Intravenous (IV) Herceptin (Trastuzumab) in Human Epidermal Growth Factor Receptor (HER) 2-Positive Early Breast Cancer — NCT01401166.
• Registry record last updated 2017-03-06; status last verified 2017-01.
• Results first posted 2015-06-08.
• 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

NCT01401166 is a completed, randomized, open-label Phase 2 crossover study sponsored by Hoffmann-La Roche. It enrolled 488 participants with HER2-positive early breast cancer. Participants received SC or IV Herceptin for Cycles 1 to 4, then crossed to the other method for Cycles 5 to 8; SC administration was studied using a single-use injection device in one cohort and a vial formulation in another. The primary endpoint asked which method participants preferred at Week 24, among those who received both routes and completed a telephone interview. The registry record does not report the primary preference result, its precision, or the detailed statistical analysis. It records serious and other adverse event counts by cohort and period, but does not report a comparative safety analysis. The study’s registry dates are 2011-10 for start and 2013-05 for primary completion.