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 Randomized, Open Label, Clinical Study of the Targeted Therapy, Palbociclib, to Treat Metastatic Breast Cancer (NCT02947685), a randomized phase 3 study. The primary outcome is Progression-free Survival (PFS) as Assessed by Investigator.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT02947685 |
| Phase | Phase 3 |
| Condition | HER-2 Positive Breast Cancer, Estrogen Receptor Positive Breast Cancer |
| Allocation | Randomized |
| Design model | Parallel |
| Masking | None (open label) |
| Enrollment | 518 |
| Arms in the primary outcome | 2 |
| Lead sponsor | Alliance Foundation Trials, LLC. |
| Results posted | Yes |
2. Clinical Question
Population
People with hormone receptor-positive, HER2-positive metastatic breast cancer after induction treatment. The registry lists HER-2-positive and estrogen receptor-positive breast cancer as conditions. Further eligibility details are not reported in the registry record.
Intervention
Palbociclib added to anti-HER2 therapy with trastuzumab and pertuzumab, plus endocrine therapy. The endocrine options listed are letrozole, anastrozole, exemestane, or fulvestrant. The arm description specifies palbociclib 125 mg daily and anti-HER2 therapy every three weeks, with treatment continuing until confirmed disease progression.
Comparator
Anti-HER2 therapy with trastuzumab and pertuzumab, plus one of the listed endocrine therapies, without palbociclib. The registry describes this treatment as continuing until confirmed disease progression.
Primary question
Does adding palbociclib to anti-HER2 and endocrine therapy improve investigator-assessed progression-free survival after induction treatment? The primary endpoint is the time from registration to disease progression or death. The posted result compares the median time in each randomized arm.
3. Trial Design
This is a randomized, open-label, parallel-group phase III trial. Participants were assigned to Arm A, which adds palbociclib to anti-HER2 and endocrine therapy, or Arm B, which receives anti-HER2 and endocrine therapy without palbociclib. The registry lists enrollment of 518. Randomization supports a comparison between treatment strategies, while the open-label design means treatment assignment was not masked.
The therapies in both arms include trastuzumab and pertuzumab as anti-HER2 treatment, and an endocrine treatment selected from letrozole, anastrozole, exemestane, or fulvestrant. Arm A additionally includes palbociclib 125 mg daily. The arm descriptions state that treatment continues until confirmed disease progression. They do not specify whether the endocrine therapy choices were randomized or how those choices were made.
The registry lists the study as active, not recruiting. Its primary completion date is 2024-10-15, and its start date is 2017-06-21. These registry fields describe study status and timing; they do not establish that follow-up or all analyses are complete. The primary outcome timeframe is listed as 7 years 3 months.
The main comparison is the investigator-assessed median progression-free survival. Secondary outcomes listed include overall survival, survival probabilities, response, duration of response, clinical benefit, adverse events, patient-reported outcomes, and CNS metastasis. The registry record does not report the trial’s detailed randomization procedures, allocation concealment, masking of outcome assessors, or the planned statistical analysis approach.
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
| Stage | Arm A | Arm B |
|---|---|---|
| STARTED | 261 | 257 |
| COMPLETED | 261 | 257 |
| NOT COMPLETED | 0 | 0 |
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.
| Characteristic | Unit | Arm A | Arm B | Total |
|---|---|---|---|---|
| Participants analysed | 261 | 257 | 518 | |
| Age, Continuous | years | 53.5 (43.6 to 60.4) | 53 (45.1 to 62.8) | 53.4 (44.2 to 61.4) |
| Sex: Female, Male: Female | Participants | 259 | 256 | 515 |
| Sex: Female, Male: Male | Participants | 2 | 1 | 3 |
| Ethnicity (NIH/OMB): Hispanic or Latino | Participants | 46 | 25 | 71 |
| Ethnicity (NIH/OMB): Not Hispanic or Latino | Participants | 120 | 136 | 256 |
| Ethnicity (NIH/OMB): Unknown or Not Reported | Participants | 95 | 96 | 191 |
| Race (NIH/OMB): American Indian or Alaska Native | Participants | 3 | 0 | 3 |
| Race (NIH/OMB): Asian | Participants | 8 | 3 | 11 |
| Race (NIH/OMB): Native Hawaiian or Other Pacific Islander | Participants | 3 | 3 | 6 |
| Race (NIH/OMB): Black or African American | Participants | 4 | 11 | 15 |
| Race (NIH/OMB): White | Participants | 207 | 194 | 401 |
| Race (NIH/OMB): More than one race | Participants | 0 | 1 | 1 |
| Race (NIH/OMB): Unknown or Not Reported | Participants | 36 | 45 | 81 |
6. Primary Endpoint
The registry lists the primary outcome as Progression-free Survival (PFS) as Assessed by Investigator, measured over 7 years 3 months.
| Element | Registry entry |
|---|---|
| Result type | Median |
| Measure of spread | 95% Confidence Interval |
| Unit | months |
| Endpoint classification | Time-to-Event Analysis |
Progression-free survival (PFS) is defined in the registry as the time from registration to disease progression or death. It combines two clinically important events into a time-to-event outcome: progression and death. Participants who have not experienced either event by their last known assessment may have incomplete follow-up for this endpoint, so the analysis generally needs to account for censoring. The registry’s detailed censoring rules are not reported in the registry record.
The primary endpoint is assessed by the investigator and summarized as a median in months, with a 95% confidence interval for each arm. The median is the point in the observed time-to-event distribution at which the estimated proportion remaining progression-free reaches one half. It describes the timing of the middle of that distribution rather than the experience of every participant or the full shape of the survival curve.
PFS is used in clinical trials because it can capture disease worsening or death before an overall-survival event is observed. It is not interchangeable with overall survival, response, or quality of life. The registry lists those as separate secondary outcomes. An investigator-assessed endpoint can also be influenced by assessment timing and judgment, particularly in an open-label study; the record does not describe independent blinded review or the assessment schedule.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The posted primary results give median investigator-assessed PFS of 44.3 months for Arm A, with a 95% confidence interval of 32.4 to 56.8 months, and 29.1 months for Arm B, with a 95% confidence interval of 23.3 to 38.6 months. These summaries describe the observed time-to-event distributions in the randomized groups. They do not, by themselves, quantify the relative rate of progression or death over follow-up.
A confidence interval conveys uncertainty around an estimated median under the analysis used. It is not a range containing every participant’s PFS time, and it is not a probability statement about the effect for an individual. The intervals should be read alongside the median estimates, not as a substitute for a direct treatment-effect analysis. The registry record does not report a hazard ratio, its confidence interval, or a sponsor-reported comparison test for the primary endpoint. A formal estimate of the relative event rate and its uncertainty therefore cannot be described from this record.
The randomized design makes the arm comparison more informative than an uncontrolled comparison, but the posted medians alone do not establish why the distributions differ or whether the observed separation is statistically reliable under the trial’s prespecified analysis. No primary-endpoint p-value or detailed analysis population is reported in the registry record. The record also does not report the numbers of progression events, censoring patterns, or the survival curve estimates needed to understand how the comparison developed over time.
Investigator assessment and open-label treatment assignment are relevant when interpreting PFS. Knowledge of assigned treatment could potentially influence decisions or timing around progression assessment. That is a general design concern, not evidence that assessments in this study were biased. The registry record does not describe blinded adjudication or safeguards that would clarify this issue.
The results should be understood as posted estimates from the study record, not as a complete account of the trial’s evidence. The registry lists other outcomes, including overall survival and safety, but their presence does not make the primary endpoint a proxy for them. Conclusions about the overall balance of benefit and harm require fuller outcome reporting and the trial’s analysis methods, neither of which can be reconstructed from the medians alone.
9. Statistical Methods Explained
The primary endpoint is a time-to-event measure. For each participant, the relevant time begins at registration and ends at disease progression or death, as defined in the registry. Participants without a recorded event by the end of their available follow-up are commonly treated as censored in survival analysis. Censoring means that the event time is not known precisely, although the participant contributes information up to the last time they were known to be event-free. The registry record does not report the censoring rules, follow-up distribution, or handling of participants who discontinue treatment or assessments.
What does a median PFS estimate describe?
A median summarizes the midpoint of a time-to-event distribution. Unlike an arithmetic average, it does not require assigning a complete event time to everyone who has not yet had an event. The reported median is a summary of the estimated distribution for each arm, rather than a comparison of paired individual outcomes. The 95% confidence interval gives a range of estimates compatible with the data and method under repeated use of that method. It does not describe the spread of individual PFS times.
The two arm-specific medians are not a hazard ratio. A hazard ratio compares event rates over time under a particular model and is often used as a treatment-effect summary for survival outcomes. It is not obtained by dividing or subtracting medians. The registry record does not report a primary PFS hazard ratio or the model used to estimate one. Without that information, proportional-hazards assumptions and the relative event rate cannot be assessed from the posted medians.
Why does follow-up and censoring matter?
Time-to-event analyses use both observed events and the time participants remain under observation without an event. When censoring is extensive or differs meaningfully between groups, estimates may be less precise or require careful interpretation. A long listed outcome timeframe does not establish that every participant was followed for that length of time. The registry record does not provide arm-specific follow-up summaries, event counts for PFS, or details of loss to follow-up.
More generally, survival curves show how the estimated proportion without an event changes over time. They can reveal whether group patterns are consistent or whether they change during follow-up. A median compresses that information into a single time point. Curve data and a reported treatment-effect model would add context, but those results are not reported in the registry record.
How should the confidence intervals be read?
Each interval expresses statistical uncertainty in an arm-specific median estimate. Precision depends on the amount and timing of event information, not simply on enrollment. An interval does not show the probability that the true median lies inside that particular realized interval, and overlap or non-overlap of two arm-specific intervals is not a substitute for a direct comparison test. The registry record does not report a confidence interval for a difference between medians.
What do the secondary binary outcomes add?
Objective response and clinical benefit are binary outcomes: each participant is classified according to whether the outcome definition was met. The registry gives arm-level proportions for the posted results. Such proportions describe how often the recorded outcome occurred in each analyzed group, but their interpretation depends on the endpoint definition, assessment window, and analysis population. The record lists a 24-month timeframe for these outcomes, but does not report detailed definitions, missing-assessment rules, or a sponsor-reported inferential analysis.
Risk differences, risk ratios, and odds ratios are different ways to contrast binary outcomes. Each has a distinct scale and interpretation. A recalculation from summary data, where displayed, is an unadjusted calculation and should not be mistaken for a prespecified sponsor analysis. The registry record lists no reported analyses for these secondary results. The listed sample-size illustrations are planning calculations based on observed effects, not observed power and not evidence that the trial was designed around those effects. They use a two-sided significance level of 0.05, equal allocation, and a normal approximation; their assumptions do not establish the trial’s actual design rationale.
10. Multiplicity, Missing Data and Analysis Populations
Multiplicity arises when a study evaluates multiple outcomes, comparisons, time points, or subgroups. Even when each analysis uses a conventional significance threshold, testing many hypotheses increases the chance of obtaining at least one apparently unusual result by chance. Trials can address this with prespecified outcome hierarchies, adjusted thresholds, or other strategies that control the overall error rate. These are general statistical approaches; the registry record does not report which, if any, were planned for this study.
The registry lists a broad set of secondary outcomes, including overall survival, survival probabilities, response measures, adverse events, patient-reported outcomes, and CNS metastasis. It does not report a testing hierarchy or multiplicity adjustment. The record also lists no reported analyses for the posted secondary results. Consequently, those secondary estimates should be treated as descriptive rather than as a collection of confirmed treatment effects. The same caution applies to exploratory analyses if any were conducted; those are not reported in the registry record.
Missing data are a separate issue from multiplicity. For time-to-event outcomes, incomplete observation is commonly handled through censoring, but validity depends on how censoring relates to the chance of an event. For binary outcomes, missing assessments may affect the denominator or classification, depending on the analysis rules. The registry record does not report the missing-data methods, the number of participants with missing outcome assessments, or sensitivity analyses addressing missingness.
Analysis populations also matter. Results may be calculated among all randomized participants, among participants who received treatment, or among another defined group. These populations answer different questions and can differ in their protection against bias. The registry record does not specify the primary or secondary analysis populations or provide participant flow by arm. No assumptions about the analysis set or missing-data procedure can therefore be made from the posted information.
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 |
|---|---|---|---|
| Arm A | 75 | 261 | 28.7% |
| Arm B | 54 | 257 | 21.0% |
Deaths
| Arm | Deaths (participants affected of at risk) |
|---|---|
| Arm A | 60 of 261 |
| Arm B | 63 of 257 |
Other (non-serious) adverse events
Participants with at least one non-serious event at or above the registry's 0% reporting threshold.
| Arm | Participants affected of at risk |
|---|---|
| Arm A | 261 of 261 |
| Arm B | 234 of 257 |
Most frequent serious adverse event terms
| Event term | Organ system | Arm A | Arm B |
|---|---|---|---|
| Infections and infestations - Oth spec | Infections and infestations | 10 of 261 | 4 of 257 |
| Fracture | Injury, poisoning and procedural complications | 6 of 261 | 3 of 257 |
| Death NOS | General disorders | 4 of 261 | 4 of 257 |
| Urinary tract infection | Infections and infestations | 5 of 261 | 2 of 257 |
| Abdominal pain | Gastrointestinal disorders | 4 of 261 | 2 of 257 |
| Gen disord and admin site conds-Oth spec | General disorders | 1 of 261 | 5 of 257 |
| Cholecystitis | Hepatobiliary disorders | 4 of 261 | 2 of 257 |
| Gastrointestinal disorders - Oth spec | Gastrointestinal disorders | 4 of 261 | 1 of 257 |
| Small intestinal obstruction | Gastrointestinal disorders | 4 of 261 | 1 of 257 |
| Lung infection | Infections and infestations | 3 of 261 | 2 of 257 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Arm A | Arm B |
|---|---|---|---|
| Diarrhea | Gastrointestinal disorders | 182 of 261 | 92 of 257 |
| Fatigue | General disorders | 135 of 261 | 96 of 257 |
| Neutrophil count decreased | Investigations | 196 of 261 | 20 of 257 |
| Arthralgia | Musculoskeletal and connective tissue disorders | 66 of 261 | 85 of 257 |
| Pain | General disorders | 58 of 261 | 62 of 257 |
| Infections and infestations - Oth spec | Infections and infestations | 83 of 261 | 35 of 257 |
| Hot flashes | Vascular disorders | 55 of 261 | 63 of 257 |
| Nausea | Gastrointestinal disorders | 75 of 261 | 40 of 257 |
| Headache | Nervous system disorders | 65 of 261 | 46 of 257 |
| Anemia | Blood and lymphatic system disorders | 84 of 261 | 24 of 257 |
Serious events with the highest arm-level rate: infections and infestations - oth spec (3.8%), fracture (2.3%), gen disord and admin site conds-oth spec (1.9%), urinary tract infection (1.9%), death nos (1.6%).
The registry reports serious adverse events affecting 75 participants in Arm A and 54 in Arm B. The corresponding groups at risk are listed as 261 and 257. These are participant counts, not event rates adjusted for time on treatment. The record also reports other adverse events affecting 261 participants in Arm A and 234 in Arm B, with the same respective group sizes at risk. A participant can experience more than one adverse event, so counts of affected participants and counts of individual events are not interchangeable.
The record lists deaths of 60 in Arm A and 63 in Arm B. It does not state in these figures whether each death was considered treatment-related, nor do the counts alone establish causation. The serious adverse event terms listed as most frequent include infections and infestations, fracture, general disorders and administration-site conditions, urinary tract infection, death not otherwise specified, and dyspnea. The listed percentages are registry-reported figures; the record does not provide arm-specific attribution for those terms in the information.
Safety comparisons require attention to definitions, exposure duration, follow-up, seriousness grading, and whether events are counted per participant or per event. The registry identifies grade 3 or higher adverse events as a secondary outcome and cites NCI CTCAE v 4.0, but the reported serious-event counts should not be treated as equivalent to that outcome. These figures describe reported safety experience and do not, by themselves, establish comparative risk or causation.
12. What the Result Does, and Does Not, Mean
The posted primary estimates describe investigator-assessed median PFS in the two randomized groups. They indicate where the midpoint of each group’s estimated time-to-event distribution lies, with uncertainty expressed by arm-specific confidence intervals. They are useful summaries of the recorded outcomes, but they do not describe every participant’s course or the full pattern of events throughout follow-up.
These results do not, on their own, quantify a relative reduction in the rate of progression or death. Such a claim would require a reported treatment-effect estimate and its uncertainty, together with the analysis details. The registry record does not report a PFS hazard ratio or a primary comparison p-value. Nor does the median comparison establish an overall-survival effect, a response effect, or a patient-reported benefit. Those are separate outcomes.
Randomization supports a structured comparison of the assigned treatment strategies, but interpretation still depends on follow-up, outcome ascertainment, missing data, analysis populations, and the prespecified analysis. Those details are not reported in the registry record. The open-label design is also relevant to investigator-assessed progression, though it does not prove that assessments were biased.
The safety counts describe reported events in each arm, not proof that a treatment caused or prevented an event. They also do not capture the full balance of clinical outcomes on their own. The record’s listed adverse-event categories and secondary outcomes provide context, but key analysis details and several numerical outcome results are not reported.
Accordingly, the appropriate reading is bounded: the registry posts arm-specific PFS medians and safety counts, with additional secondary outcomes listed. These data support description of the trial record, but a complete judgment about the comparative evidence requires the sponsor’s full analysis and comprehensive outcome reporting. No medical decision follows from these summaries alone.
13. Why This Trial Matters Statistically
This trial is statistically notable because it randomizes participants between two treatment strategies that share anti-HER2 and endocrine therapy, with palbociclib added in one arm. That design makes the central question an incremental-treatment comparison rather than a comparison of unrelated regimens. The investigator-assessed PFS endpoint is a time-to-event outcome, so its interpretation depends on event timing, censoring, follow-up, and the method used to compare groups.
The registry reports medians and confidence intervals, but not a primary hazard ratio or direct comparison test. This makes it possible to describe the arm-specific estimates while also illustrating why an endpoint summary is not the same as a complete treatment-effect analysis. The confidence intervals communicate uncertainty in each median; they do not directly provide uncertainty for a contrast between arms.
The study also illustrates why outcome families need to be considered together without treating every result as equally confirmatory. Survival, response, safety, and patient-reported outcomes address different questions. Where many outcomes are listed, multiplicity and analysis-population choices affect how much weight to place on apparent patterns. The registry record does not report the detailed statistical plan needed to resolve those issues.
Finally, the distinction between planning assumptions and observed evidence matters. Sample-size illustrations based on observed effects are not observed power and do not reveal the original rationale for enrollment. The registry lists enrollment of 518, but the sample-size justification and trial-specific design assumptions are not reported in the registry record. This separates what the posted results describe from what would be needed for a full statistical appraisal.
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.
Several limitations specific to this trial record constrain interpretation. The primary result is an investigator-assessed median, but no hazard ratio, direct comparison test, PFS event count, survival curve, or arm-specific follow-up summary is reported in the registry record. Without these, the relative event-rate estimate, its precision, and the evolution of outcomes over time cannot be assessed from the posted primary summary.
The study is open-label, and the primary endpoint depends on investigator assessment of disease progression. This makes assessment procedures relevant to interpretation. The registry record does not report whether progression was independently reviewed, whether reviewers were blinded, or how assessment timing was standardized. This limitation identifies uncertainty in the record; it is not evidence that the outcome assessment was biased.
Important operational details are not reported in the registry record, including the randomization method, allocation concealment, detailed eligibility criteria, analysis populations, censoring rules, missing-data procedures, and sensitivity analyses. The status is active, not recruiting, and the primary completion date is listed, but these fields alone do not establish that every analysis or follow-up period is complete.
The registry lists multiple secondary outcomes, while numerical results are not reported for several of them. It also does not report a multiplicity strategy or a testing hierarchy. As a result, secondary outcomes cannot be treated as a coherent set of confirmatory tests based on this record alone. Safety counts also lack detail on exposure-adjusted comparisons and causal attribution. These gaps make the posted summaries useful for orientation but insufficient for a comprehensive assessment of efficacy and safety.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Randomized, Open Label, Clinical Study of the Targeted Therapy, Palbociclib, to Treat Metastatic Breast Cancer — NCT02947685.
- Registry record last updated 2026-10-22; status last verified 2026-02.
- Results first posted 2026-02-12.
- 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
The registry describes a randomized, open-label, parallel-group phase III trial of palbociclib added to anti-HER2 and endocrine therapy versus anti-HER2 and endocrine therapy alone for HR-positive, HER2-positive metastatic breast cancer after induction treatment. Enrollment is listed as 518, and the study status is active, not recruiting.
The primary outcome is investigator-assessed PFS, defined as time from registration to disease progression or death. Posted median estimates are 44.3 months for Arm A and 29.1 months for Arm B, each with a 95% confidence interval. The record also includes secondary outcomes and safety counts, but does not report a primary hazard ratio, comparison test, detailed analysis plan, or several key follow-up and missing-data details.