This page provides an independent statistical analysis and educational interpretation of publicly reported results. ClinicalTrials.gov provides the official trial registry record. Numerical trial results on this page are restricted to the results posted in the ClinicalTrials.gov record; calculations added by Clinical Biostats are labelled as such.
1. Trial at a Glance
This page covers the registry results for A Study to Evaluate Patient Preference and Satisfaction of Subcutaneous Administration of the Fixed-Dose Combination of Pertuzumab and Trastuzumab in Participants With HER2-Positive Early Breast Cancer (NCT03674112), a randomized phase 2 study. The primary outcome is Percentage of Participants by Their Preferred Method of Pertuzumab and Trastuzumab Administration, as Assessed in Question 1 of the Patient Preference Questionnaire (PPQ).
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT03674112 |
| Phase | Phase 2 |
| Condition | HER2-Positive Early Breast Cancer |
| Allocation | Randomized |
| Design model | Crossover |
| Masking | None (open label) |
| Enrollment | 160 |
| Arms in the primary outcome | n/a |
| Lead sponsor | Hoffmann-La Roche |
| Results posted | Yes |
2. Clinical Question
Population
Adults with HER2-positive early breast cancer who had completed neoadjuvant chemotherapy with pertuzumab and trastuzumab and undergone surgery. The primary endpoint population was more specific: randomized participants who received at least one dose by both routes during the Treatment Cross-over Period and then answered at least Question 1 of the Patient Preference Questionnaire.
Intervention
The subcutaneous fixed-dose combination of pertuzumab and trastuzumab, referred to as PH FDC SC. Participants received it during the crossover period and could also choose it during the treatment continuation period.
Comparator
Pertuzumab and trastuzumab administered intravenously as separate formulations, referred to as P+H IV. The randomized sequence determined whether participants received IV treatment or PH FDC SC first during the crossover period.
Primary question
At Cycle 6 Day 1, which administration method did participants prefer, considering all aspects of treatment: IV, SC, or no preference? The primary endpoint was the percentage preferring PH FDC SC, with an exact Clopper-Pearson binomial confidence interval. The registry record describes the question and planned estimate but does not report the observed percentage or interval.
The trial addressed a preference question rather than a direct comparison of clinical benefit. It also collected participant-reported satisfaction and quality-of-life measures, healthcare professionals’ perceptions of convenience and time or resource use, and safety and efficacy outcomes. Preference may reflect the overall experience of receiving treatment, not just the route itself. The registry record does not report the factors participants considered when choosing a response to the primary question, beyond the wording “All things considered.”
3. Trial Design
This was a Phase II, randomized, multicenter, multinational, open-label crossover study in participants with HER2-positive early breast cancer. The registry record lists planned enrollment of 160 participants and the study status as completed. Participants were randomized to one of two treatment sequences: P+H IV followed by PH FDC SC, or PH FDC SC followed by P+H IV. The registry describes a Treatment Cross-over Period followed by a Treatment Continuation Period.
In a crossover design, participants receive more than one intervention in sequence. This makes it possible to collect experience with both routes from the same participant, which is relevant when the outcome is an individual preference. Randomizing the order helps avoid assigning one route to every participant first. However, the registry record does not report whether order effects, carryover, or period effects were assessed in the primary analysis.
The study was open-label, so participants and study personnel were not masked to the administration route. That is inherent in the practical experience being evaluated, but awareness of the route can influence reported preference or satisfaction. The primary questionnaire was administered at Cycle 6 Day 1, and each cycle was 21 days. The description indicates a crossover between the routes, but does not report all operational details of treatment administration or the analysis approach for the crossover sequence.
The primary endpoint population was the modified Intent-to-Treat population, defined as randomized participants who received at least one dose by both routes during the crossover period and subsequently answered at least Question 1 of the Patient Preference Questionnaire. This differs from an analysis of every randomized participant: it excludes those who did not satisfy the treatment-exposure and questionnaire-response criteria. The registry record does not report how many participants met those criteria or how their number differed from the randomized enrollment.
Although the stated study purpose also included safety, efficacy, satisfaction, and healthcare professional assessments, the registry record does not report the results for the primary preference outcome. The analysis records count is zero. The record also does not report the protocol’s sample-size justification or enough statistical detail to reconstruct the primary analysis beyond its stated binomial estimate and confidence interval.
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.
Treatment Cross-Over (Cycles 1 to 6)
| Stage | A: P+H IV Followed by PH FDC SC | B: PH FDC SC Followed by P+H IV |
|---|---|---|
| STARTED | 80 | 80 |
| Completed Cross-Over Treatment | 80 | 80 |
| COMPLETED | 79 | 80 |
| NOT COMPLETED | 1 | 0 |
Reasons for not completing this period:
| Reason | A: P+H IV Followed by PH FDC SC | B: PH FDC SC Followed by P+H IV |
|---|---|---|
| Adverse Event | 1 | 0 |
Treatment Continuation (Cycles 7 to ≤18)
| Stage | A: P+H IV Followed by PH FDC SC | B: PH FDC SC Followed by P+H IV |
|---|---|---|
| STARTED | 79 | 80 |
| Received PH FDC SC for Treatment Continuation | 70 | 68 |
| Received P+H IV for Treatment Continuation | 9 | 12 |
| Completed Continuation Treatment | 78 | 77 |
| COMPLETED | 78 | 77 |
| NOT COMPLETED | 1 | 3 |
Reasons for not completing this period:
| Reason | A: P+H IV Followed by PH FDC SC | B: PH FDC SC Followed by P+H IV |
|---|---|---|
| Reason Not Specified | 0 | 2 |
| Withdrawal by Subject | 0 | 1 |
| Disease Relapse | 1 | 0 |
Follow-Up Period (≥3 Years)
| Stage | A: P+H IV Followed by PH FDC SC | B: PH FDC SC Followed by P+H IV |
|---|---|---|
| STARTED | 80 | 79 |
| COMPLETED | 73 | 75 |
| NOT COMPLETED | 7 | 4 |
Reasons for not completing this period:
| Reason | A: P+H IV Followed by PH FDC SC | B: PH FDC SC Followed by P+H IV |
|---|---|---|
| Withdrawal by Subject | 2 | 2 |
| Lost to Follow-up | 2 | 1 |
| Death | 2 | 0 |
| Reason Not Specified | 1 | 1 |
Analysis population for the primary outcome, as defined in the registry: Modified Intent-to-Treat (mITT) Population: All randomized participants, allocated to their randomized treatment arm, who received at least one dose by both SC and IV routes of administration during the Treatment Cross-over Period and subsequently answered at least Question 1 of the PPQ.
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: includes all randomized participants, allocated to their randomized treatment arm, whether or not the assigned study treatment was received.
| Characteristic | Unit | A: P+H IV Followed by PH FDC SC | B: PH FDC SC Followed by P+H IV | Total |
|---|---|---|---|---|
| Participants analysed | 80 | 80 | 160 | |
| Age, Continuous | Years | 49.4 (SD 11.6) | 48.2 (SD 12.1) | 48.8 (SD 11.8) |
| Sex: Female, Male: Female | Participants | 80 | 80 | 160 |
| Sex: Female, Male: Male | Participants | 0 | 0 | 0 |
| Ethnicity (NIH/OMB): Hispanic or Latino | Participants | 17 | 21 | 38 |
| Ethnicity (NIH/OMB): Not Hispanic or Latino | Participants | 59 | 54 | 113 |
| Ethnicity (NIH/OMB): Unknown or Not Reported | Participants | 4 | 5 | 9 |
| Race (NIH/OMB): American Indian or Alaska Native | Participants | 5 | 3 | 8 |
| Race (NIH/OMB): Asian | Participants | 8 | 4 | 12 |
| Race (NIH/OMB): Native Hawaiian or Other Pacific Islander | Participants | 0 | 0 | 0 |
| Race (NIH/OMB): Black or African American | Participants | 2 | 2 | 4 |
| Race (NIH/OMB): White | Participants | 62 | 67 | 129 |
| Race (NIH/OMB): More than one race | Participants | 0 | 0 | 0 |
| Race (NIH/OMB): Unknown or Not Reported | Participants | 3 | 4 | 7 |
| Baseline Weight | kilograms (kg) | 67.36 (SD 12.08) | 70.21 (SD 14.15) | 68.78 (SD 13.20) |
| Eastern Cooperative Oncology Group (ECOG) Performance Status at Baseline: ECOG Peformance Status 0 | Participants | 70 | 70 | 140 |
| Eastern Cooperative Oncology Group (ECOG) Performance Status at Baseline: ECOG Peformance Status 1 | Participants | 10 | 10 | 20 |
| Number of Cycles of Prior Neoadjuvant Pertuzumab IV and Trastuzumab IV: <4 Cycles | Participants | 5 | 10 | 15 |
| Number of Cycles of Prior Neoadjuvant Pertuzumab IV and Trastuzumab IV: ≥4 Cycles | Participants | 75 | 70 | 145 |
| Prior Neoadjuvant Chemotherapy Regimen: Anthracyclines + Taxanes | Participants | 55 | 53 | 108 |
| Prior Neoadjuvant Chemotherapy Regimen: Carboplatin + Taxanes | Participants | 22 | 23 | 45 |
| Prior Neoadjuvant Chemotherapy Regimen: Taxanes Only | Participants | 3 | 4 | 7 |
| Pathological Complete Response (pCR) to Prior Neoadjuvant Treatment: pCR | Participants | 52 | 50 | 102 |
| Pathological Complete Response (pCR) to Prior Neoadjuvant Treatment: Non-pCR | Participants | 28 | 30 | 58 |
| Hormone Receptor Status: Estrogen Receptor (ER)-Positive and/or Progesterone Receptor (PgR)-Positive | Participants | 53 | 51 | 104 |
| Hormone Receptor Status: ER-Negative and PgR-Negative | Participants | 27 | 29 | 56 |
6. Primary Endpoint
The registry lists the primary outcome as Percentage of Participants by Their Preferred Method of Pertuzumab and Trastuzumab Administration, as Assessed in Question 1 of the Patient Preference Questionnaire (PPQ), measured over Cycle 6 Day 1 (each cycle is 21 days).
| Element | Registry entry |
|---|---|
| Result type | Number |
| Measure of spread | 95% Confidence Interval |
| Unit | Percentage of participants |
| Endpoint classification | Binary Endpoint |
The primary endpoint was the percentage of participants who preferred PH FDC SC, assessed with Question 1 of the Patient Preference Questionnaire at Cycle 6 Day 1. Participants could answer IV, SC, or no preference. The endpoint focused on the percentage choosing SC; it was not described as a comparison of all response categories using a single overall test.
Preference is a participant-reported outcome. It captures the participant’s stated choice after experience with both routes, which is directly relevant to a study asking how patients view alternative ways to receive treatment. It differs from an objective measure of treatment efficacy and does not, by itself, establish that one route is clinically better. Nor does an estimate of preference describe the reasons for that preference; the study listed separate questionnaire outcomes about reasons and satisfaction.
The registry specifies an exact Clopper-Pearson binomial 95% confidence interval for the percentage preferring PH FDC SC. In general, a confidence interval conveys the precision of an estimated proportion: a narrower interval indicates greater precision, while a wider interval indicates more uncertainty. The actual percentage and interval are not reported in the registry record, so the size and precision of the observed preference cannot be assessed from this record.
The endpoint was evaluated in a modified Intent-to-Treat population requiring exposure to both routes and a response to the preference question. Thus, the measure concerns participants meeting those criteria, not necessarily everyone randomized. The registry record does not report the number included in this population or how missing questionnaire responses were handled.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The registry record identifies a randomized crossover study designed to compare participant preference after exposure to both subcutaneous PH FDC SC and intravenous P+H IV. It gives the primary question, its response options, the analysis population definition, and the planned confidence interval method. It does not give the observed percentage preferring PH FDC SC or its 95% confidence interval. Therefore, the primary result and its precision are not reported in the registry record, and no conclusion about the distribution of participant preferences can be drawn from the posted results.
The record lists 45 outcome measures and zero analysis records. The secondary outcomes include preference strength and reasons, satisfaction measures, five domains of satisfaction, physical and psychological impact, activities of daily living, convenience, and responses about time with clinicians. It also lists treatment choice during the continuation period and whether that choice was consistent with the reported preference. These outcomes could provide different perspectives on treatment experience, but their observed results are not reported in the registry record.
Interpretation of the primary endpoint would depend on both the estimated percentage and its confidence interval, as well as the number of participants included. A point estimate alone would not show how uncertain the result was. The interval would characterize sampling uncertainty under the stated binomial approach, but would not address possible response bias, open-label expectations, or limitations arising from excluding people who did not receive both routes or answer the questionnaire.
The crossover structure is useful for preference research because participants can experience both methods. At the same time, treatment sequence and period may affect reports: the first method experienced could shape later judgments, and preference at the questionnaire assessment may reflect the sequence or the treatment period. These are general considerations for crossover studies. Whether the registry analysis accounted for such effects is not reported in the registry record.
Safety counts are posted separately for several treatment periods. During the Treatment Cross-over Period, the record reports 6 participants with serious adverse events among 160 at risk for P+H IV and 2 among 160 at risk for PH FDC SC. During the Treatment Continuation Period, it reports 0 among 21 at risk for P+H IV and 4 among 138 at risk for PH FDC SC. Across all study treatment periods, it reports 11 among 160 participants for serious adverse events and 125 among 160 for other adverse events. These are counts, not a randomized comparison adjusted for exposure, sequence, or time. The registry record does not report a statistical comparison for these safety figures.
The record reports 0 deaths in each listed treatment-period group and 2 deaths among 159 participants in the Follow-Up Period. Such counts should be read in their stated periods and groups; they do not replace a full assessment of event timing, duration of exposure, or clinical context. The serious adverse event terms listed with percentages are reported as recorded, but the registry entry does not provide enough detail to infer a causal relationship or compare risks reliably. In general, adverse-event counts describe events observed and recorded in the specified groups; they are not, on their own, proof of cause.
9. Statistical Methods Explained
The primary endpoint is a proportion: among participants in the defined analysis population, the statistic of interest is the percentage choosing PH FDC SC. Each participant’s response to Question 1 falls into one of three listed categories—IV, SC, or no preference—but the registry describes a point estimate and confidence interval only for the SC-preferring percentage. The record does not report the number of participants in the primary analysis or the observed count choosing SC.
What does a binomial confidence interval express?
In general, a binomial model describes outcomes with two possibilities for the particular calculation: the response of interest occurs or it does not. Here, the stated calculation concerns whether a participant preferred PH FDC SC. The exact Clopper-Pearson interval is a method for placing a confidence interval around a binomial proportion. A confidence interval communicates uncertainty in an estimate arising from the finite set of observed participants. It does not indicate that individual preferences vary within the interval, and it does not account automatically for every possible source of bias.
The registry specifies a 95% confidence interval and the exact Clopper-Pearson method. It does not report the resulting estimate or interval. Without those results and the analysis denominator, the magnitude and precision of the primary finding cannot be interpreted. The absence of a posted estimate should not be replaced by an inference from the study design, planned enrollment, or secondary outcome descriptions.
What is important about the crossover?
In general, a crossover study assigns participants to a sequence of interventions, so each participant may experience both. A within-participant comparison can reduce the influence of stable differences between people when outcomes are measured under both conditions. For a stated preference outcome, experiencing both routes also gives participants a basis for choosing between them. In this trial, the randomized sequences were P+H IV followed by PH FDC SC and PH FDC SC followed by P+H IV.
Crossover designs require attention to order and period. A participant’s experience in an earlier period can influence a later response; this is often called a carryover effect. The treatment period itself can also matter, and the sequence may shape which method is remembered most strongly. These are general design considerations, not claims that such effects occurred in this trial. The registry record does not report whether the primary analysis adjusted for sequence, period, or carryover, or how incomplete crossover participation was handled.
The trial was open-label. In general, knowing which route is being received can influence subjective reports such as preference, satisfaction, or perceived convenience. Masking is difficult when routes of administration are visibly different. The registry record does not report an assessment of expectation effects or other methods used to reduce reporting bias.
How should the analysis population be understood?
The modified Intent-to-Treat population included randomized participants allocated to their randomized arm who received at least one dose by both SC and IV routes during the Treatment Cross-over Period and later answered at least Question 1. This definition makes receipt of both treatments and a questionnaire response prerequisites for inclusion in the primary analysis. It is therefore narrower than simply including everyone randomized. In general, excluding participants after randomization can affect how representative an estimate is of the original randomized population, particularly if the reasons for exclusion relate to treatment experience or outcome reporting. The registry record does not report the number excluded, the reasons, or an analysis retaining all randomized participants.
Questionnaire nonresponse is relevant because the primary endpoint is participant-reported. The record defines the required response but does not report how missing responses were handled, whether imputation was used, or whether sensitivity analyses were conducted. It also does not report whether a participant with no preference was treated in any additional analysis of the SC-preferring proportion; the endpoint description simply identifies the estimated percentage as those preferring PH FDC SC.
What can the safety counts establish?
Adverse-event summaries are organized by treatment period and exposure group. The cross-over groups each list 160 participants at risk, while the continuation groups list 21 for P+H IV and 138 for PH FDC SC. The all-treatment-period summary lists 160 participants, and the follow-up group lists 159. Counts across these different periods should not be combined or interpreted as if all groups were parallel randomized arms with equivalent exposure. In general, event counts can be influenced by exposure duration and the way participants contribute to different periods. The registry record does not provide exposure-adjusted comparisons or statistical tests for these summaries.
The trial record also gives planning assumptions for illustrations based on the observed effect, including a two-sided significance level of 0.05, equal allocation, and a normal approximation. Such planning illustrations are not observed power and do not establish the trial’s original design rationale. The protocol’s own sample-size justification is not reported in the registry record. The reported analysis-record count is zero, and the primary endpoint result itself is not reported, so the posted information does not support a reconstruction of the trial’s inferential analysis.
10. Multiplicity, Missing Data and Analysis Populations
The registry record lists 45 outcome measures, spanning the primary preference endpoint and multiple secondary measures of preference, satisfaction, quality of life, clinician interaction, treatment choice, safety, and efficacy. When a study assesses many outcomes, the chance of obtaining at least one apparently notable result by chance can increase. In general, multiplicity procedures may be used to control the interpretation of multiple statistical tests, but the registry record does not report whether any adjustment was planned or used. It also reports zero analysis records, so no set of test results or analysis details is available to assess.
The primary endpoint is described as a percentage preferring PH FDC SC with an exact Clopper-Pearson 95% confidence interval. The estimate and interval are not reported in the registry record. No p-value or formal comparison for the primary preference endpoint is reported. The record does not report a prespecified hierarchy among the secondary outcomes or explain how their results were intended to be interpreted together.
The primary analysis population required treatment by both routes and a response to the preference question. The record does not report the number of participants meeting these criteria, the number with missing questionnaire data, reasons for missingness, or methods for handling missing responses. It also does not report sensitivity analyses addressing missing data or departures from the defined analysis population.
Planning illustrations based on an observed effect are distinct from the trial’s original sample-size rationale. The registry record does not report the protocol’s sample-size justification, and planning illustrations should not be interpreted as observed power. The methods used to analyze the secondary outcomes, including any adjustments for multiple testing or crossover sequence, are not reported in the registry record.
11. Safety Results
The registry reports serious adverse events as affected participants divided by participants at risk.
| Arm | Participants with serious adverse events | Participants at risk | Percentage |
|---|---|---|---|
| P+H IV: Treatment Cross-Over Period | 6 | 160 | 3.8% |
| PH FDC SC: Treatment Cross-Over Period | 2 | 160 | 1.2% |
| P+H IV: Treatment Continuation Period | 0 | 21 | 0.0% |
| PH FDC SC: Treatment Continuation Period | 4 | 138 | 2.9% |
| All Participants: All Study Treatment Periods | 11 | 160 | 6.9% |
| Follow-Up Period | 1 | 159 | 0.6% |
Deaths
| Arm | Deaths (participants affected of at risk) |
|---|---|
| P+H IV: Treatment Cross-Over Period | 0 of 160 |
| PH FDC SC: Treatment Cross-Over Period | 0 of 160 |
| P+H IV: Treatment Continuation Period | 0 of 21 |
| PH FDC SC: Treatment Continuation Period | 0 of 138 |
| All Participants: All Study Treatment Periods | 0 of 160 |
| Follow-Up Period | 2 of 159 |
Other (non-serious) adverse events
Participants with at least one non-serious event at or above the registry's 5% reporting threshold.
| Arm | Participants affected of at risk |
|---|---|
| P+H IV: Treatment Cross-Over Period | 62 of 160 |
| PH FDC SC: Treatment Cross-Over Period | 84 of 160 |
| P+H IV: Treatment Continuation Period | 10 of 21 |
| PH FDC SC: Treatment Continuation Period | 47 of 138 |
| All Participants: All Study Treatment Periods | 125 of 160 |
| Follow-Up Period | 2 of 159 |
Most frequent serious adverse event terms
| Event term | Organ system | P+H IV: Treatment Cross-Over Period | PH FDC SC: Treatment Cross-Over Period | P+H IV: Treatment Continuation Period | PH FDC SC: Treatment Continuation Period | All Participants: All Study Treatment Periods | Follow-Up Period |
|---|---|---|---|---|---|---|---|
| Erysipelas | Infections and infestations | 1 of 160 | 0 of 160 | 0 of 21 | 2 of 138 | 2 of 160 | 0 of 159 |
| Device related infection | Infections and infestations | 1 of 160 | 0 of 160 | 0 of 21 | 1 of 138 | 2 of 160 | 0 of 159 |
| Ejection fraction decreased | Investigations | 1 of 160 | 1 of 160 | 0 of 21 | 0 of 138 | 2 of 160 | 0 of 159 |
| Breast cellulitis | Infections and infestations | 1 of 160 | 0 of 160 | 0 of 21 | 0 of 138 | 1 of 160 | 0 of 159 |
| Bronchopulmonary aspergillosis | Infections and infestations | 0 of 160 | 0 of 160 | 0 of 21 | 1 of 138 | 1 of 160 | 0 of 159 |
| Pneumonia | Infections and infestations | 1 of 160 | 0 of 160 | 0 of 21 | 0 of 138 | 1 of 160 | 0 of 159 |
| Upper respiratory tract infection | Infections and infestations | 1 of 160 | 0 of 160 | 0 of 21 | 0 of 138 | 1 of 160 | 0 of 159 |
| Asthma | Respiratory, thoracic and mediastinal disorders | 0 of 160 | 1 of 160 | 0 of 21 | 0 of 138 | 1 of 160 | 0 of 159 |
| COVID-19 | Infections and infestations | 0 of 160 | 0 of 160 | 0 of 21 | 1 of 138 | 1 of 160 | 0 of 159 |
| Cardiac failure | Cardiac disorders | 0 of 160 | 0 of 160 | 0 of 21 | 0 of 138 | 0 of 160 | 1 of 159 |
Most frequent non-serious adverse event terms
| Event term | Organ system | P+H IV: Treatment Cross-Over Period | PH FDC SC: Treatment Cross-Over Period | P+H IV: Treatment Continuation Period | PH FDC SC: Treatment Continuation Period | All Participants: All Study Treatment Periods | Follow-Up Period |
|---|---|---|---|---|---|---|---|
| Injection site reaction | General disorders | 0 of 160 | 36 of 160 | 0 of 21 | 13 of 138 | 44 of 160 | 0 of 159 |
| Radiation skin injury | Injury, poisoning and procedural complications | 27 of 160 | 17 of 160 | 0 of 21 | 1 of 138 | 44 of 160 | 0 of 159 |
| Diarrhoea | Gastrointestinal disorders | 17 of 160 | 15 of 160 | 4 of 21 | 15 of 138 | 37 of 160 | 0 of 159 |
| Arthralgia | Musculoskeletal and connective tissue disorders | 6 of 160 | 8 of 160 | 3 of 21 | 6 of 138 | 23 of 160 | 1 of 159 |
| Fatigue | General disorders | 8 of 160 | 9 of 160 | 1 of 21 | 7 of 138 | 19 of 160 | 0 of 159 |
| Hot flush | Vascular disorders | 6 of 160 | 9 of 160 | 0 of 21 | 3 of 138 | 16 of 160 | 0 of 159 |
| Pruritus | Skin and subcutaneous tissue disorders | 7 of 160 | 3 of 160 | 0 of 21 | 7 of 138 | 14 of 160 | 0 of 159 |
| Myalgia | Musculoskeletal and connective tissue disorders | 6 of 160 | 3 of 160 | 2 of 21 | 1 of 138 | 12 of 160 | 1 of 159 |
| Headache | Nervous system disorders | 3 of 160 | 5 of 160 | 2 of 21 | 1 of 138 | 10 of 160 | 0 of 159 |
| Pain in extremity | Musculoskeletal and connective tissue disorders | 1 of 160 | 4 of 160 | 2 of 21 | 4 of 138 | 9 of 160 | 1 of 159 |
Serious events with the highest arm-level rate: erysipelas (1.4%), device related infection (1.2%), ejection fraction decreased (1.2%), bronchopulmonary aspergillosis (0.7%), covid-19 (0.7%).
During the Treatment Cross-over Period, serious adverse events were reported for 6 participants in the P+H IV group and 2 in the PH FDC SC group; each group lists 160 participants at risk. Other adverse events were reported for 62 and 84 participants, respectively. During the Treatment Continuation Period, the P+H IV group lists 0 serious and 10 other adverse events among 21 at risk, while the PH FDC SC group lists 4 serious and 47 other adverse events among 138 at risk. Across all study treatment periods, the record lists 11 participants with serious adverse events and 125 with other adverse events among 160 participants. These figures are counts of participants with events, not counts of individual events.
The follow-up group lists 1 participant with a serious adverse event and 2 with other adverse events among 159 at risk, with 2 deaths reported. No deaths are listed for the treatment-period groups. Serious adverse event terms with reported percentages include erysipelas at 1.4%, device related infection at 1.2%, ejection fraction decreased at 1.2%, bronchopulmonary aspergillosis at 0.7%, COVID-19 at 0.7%, and cardiac failure at 0.6%.
These summaries cover distinct periods and groups, so they should be read with their stated denominators rather than treated as a single head-to-head safety comparison. The registry record does not report exposure-adjusted analyses, statistical tests, or enough context to determine causality. In general, adverse events recorded during treatment do not by themselves establish that treatment caused them.
12. What the Result Does, and Does Not, Mean
The study asks a direct question about how participants prefer to receive pertuzumab and trastuzumab after experiencing both subcutaneous and intravenous administration. The randomized crossover sequences and the participant-reported questionnaire are suited to gathering treatment-experience information. However, the registry record does not report the observed primary preference percentage or its confidence interval. It therefore does not show what proportion preferred PH FDC SC or how precisely that proportion was estimated.
Even if a preference estimate were available, it would describe the responses of participants who met the modified Intent-to-Treat criteria and answered the questionnaire. It would not automatically describe every randomized participant or all people with HER2-positive early breast cancer. The registry record does not report how many participants were included in the primary analysis or how missing responses were addressed.
Preference and satisfaction are distinct from efficacy. A preference response indicates which administration method a participant chose; it does not establish that one formulation has greater antitumor effect or is clinically superior. Likewise, the safety counts are descriptive and do not, by themselves, establish that an event was caused by a particular administration route. No comparative statistical analysis of the posted safety counts is reported.
The secondary outcomes were intended to describe reasons for preference, satisfaction across several domains, clinician interaction, and later treatment choices. Their presence in the registry clarifies the breadth of the study questions, but their results are not reported in the registry record. As a result, the posted information cannot establish whether preference aligned with convenience, satisfaction, treatment continuation choice, or other aspects of patient experience.
The most defensible interpretation is limited to the design and outcome definitions: this was an open-label randomized crossover study of administration preference and related outcomes, with a specified primary endpoint and a defined analysis population. The primary outcome result, statistical comparisons, and details needed to judge missingness and crossover effects are not reported in the registry record.
13. Why This Trial Matters Statistically
Patient preference is a distinct statistical and clinical research question. Trials often focus on efficacy or safety, while this study also sought to measure how participants experienced alternative administration methods. A preference endpoint can inform understanding of treatment burden and acceptability, but it must be interpreted as a participant-reported outcome rather than as a substitute for measures of clinical benefit.
The crossover design is relevant because each participant was intended to experience both routes before reporting a preference. In general, this can make preference comparisons more directly grounded in individual experience than asking participants to choose without exposure. Randomizing the order can help address systematic differences in which route is encountered first. At the same time, interpretation depends on how period and sequence effects are handled, and those analysis details are not reported in the registry record.
The registry also makes clear why the analysis population matters. Participants had to receive both routes and answer the primary questionnaire to be included. That definition focuses the endpoint on people with experience of both methods, while potentially excluding participants who did not complete the crossover or questionnaire. The record does not report the size or characteristics of the resulting population.
Statistically, the primary endpoint is a proportion with an exact confidence interval, making precision central to interpretation. Yet the estimate and interval are not reported. The large set of listed outcomes also raises the importance of knowing which analyses were prespecified and how multiple results were to be interpreted; those details are not reported in the registry record. The posted safety counts offer descriptive context but do not provide a formal comparative analysis.
This study is therefore informative as an example of a trial built around treatment preference, but the registry information available does not permit evaluation of the primary result. Design and endpoint definitions can be described; the degree of preference and its uncertainty cannot be inferred without the unreported 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 central limitation for interpreting the trial from the registry record is that the primary preference estimate and its confidence interval are not reported. Although the endpoint, response options, assessment time, and confidence interval method are described, the actual result cannot be evaluated. The analysis-record count is zero, and the record does not report a formal comparison for the primary endpoint.
The primary analysis population required randomized participants to receive both routes during the crossover period and answer the preference question. The registry record does not report how many participants met those requirements, how many were excluded, or why. Because the endpoint depends on a questionnaire response, missing responses and exclusions could affect how well the analyzed group represents all randomized participants. Missing-data methods and sensitivity analyses are not reported.
The open-label design is a further consideration for subjective outcomes such as preference and satisfaction. Participants knew which administration method they received. In general, that awareness can influence reporting, though the registry record does not report whether such influence was assessed. The crossover design also makes sequence and period effects relevant; whether the analysis addressed these effects is not reported.
The record lists many outcomes, but does not report a multiplicity strategy, an outcome hierarchy, or analysis details for the secondary measures. It also does not report the trial’s protocol-based sample-size justification. Safety counts are presented by treatment period and group, but the registry record does not report exposure-adjusted comparisons or statistical tests. Counts from the different periods should not be treated as a simple randomized comparison, particularly because the continuation groups have different numbers at risk.
Finally, the posted record does not provide the outcome results needed to judge efficacy, satisfaction, or the distribution of preference. These limitations concern the information reported in the registry record and do not establish that the underlying trial lacked analyses or additional results.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: A Study to Evaluate Patient Preference and Satisfaction of Subcutaneous Administration of the Fixed-Dose Combination of Pertuzumab and Trastuzumab in Participants With HER2-Positive Early Breast Cancer — NCT03674112.
- Registry record last updated 2024-01-02; status last verified 2023-12.
- Results first posted 2021-04-26.
- 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.
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18. Record Summary
NCT03674112 is a completed Phase II randomized, multicenter, multinational, open-label crossover study in HER2-positive early breast cancer. Planned enrollment was 160. Participants were assigned to receive P+H IV followed by PH FDC SC, or PH FDC SC followed by P+H IV, during the Treatment Cross-over Period. The primary endpoint was the percentage preferring PH FDC SC on Question 1 of the Patient Preference Questionnaire at Cycle 6 Day 1, with an exact Clopper-Pearson 95% confidence interval.
The primary population required exposure to both routes and a response to the preference question. The registry lists 45 outcome measures and zero analysis records. The primary estimate, confidence interval, and details on missing-data handling, multiplicity, and crossover analysis are not reported in the registry record. Safety counts are reported by treatment period, alongside selected serious adverse event terms and percentages.