Palbociclib in Combination With Adjuvant Endocrine Therapy for Hormone Receptor Positive, HER2 Negative Invasive Breast Cancer: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Palbociclib in Combination With Adjuvant Endocrine Therapy for Hormone Receptor Positive, HER2 Negative Invasive Breast Cancer (NCT02040857), a na phase 2 study. The primary outcome is 2-Year Treatment Discontinuation Rate.

2. Clinical Question

3. Trial Design

This was a Phase 2 pilot feasibility study conducted by Dana-Farber Cancer Institute. The registry reports a single-group design, with no masking and no randomized allocation. Enrollment was 162. The trial is marked completed, with a start date of 2014-01 and primary completion in 2018-05. The record does not give a separate control group or describe a randomized treatment contrast. Consequently, the design is suited to describing experience in the treated group, rather than estimating a comparative effect against an untreated or differently treated group.

Participants received palbociclib with adjuvant endocrine therapy. The listed palbociclib schedule was 125 mg by mouth daily for 21 days, followed by 7 days off. The endocrine therapy choices were tamoxifen 20mg, letrozole 2.5mg, anastrozole 1mg, or exemestane 25mg, taken by mouth daily. The summary describes tamoxifen or an aromatase inhibitor as the endocrine therapy options. The registry record does not report how participants were assigned among the endocrine therapy options or whether the listed choices were selected according to a specific protocol rule.

The primary endpoint is a percentage of participants, with a 95% confidence interval specified as the measure of dispersion. It concerns discontinuation of palbociclib for reasons tied to toxicity, consent to treatment, or tolerability, and is evaluated over a period of up to 2 years. The endpoint population is all uncensored participants. The registry also lists secondary outcomes involving discontinuation by endocrine-therapy subgroup and treatment-related neutropenia, fatigue, and alopecia. Results for these outcomes are not reported in the registry record.

The record does not report the protocol’s sample-size justification, a detailed statistical analysis plan, or a description of interim analyses. A single-group feasibility design can characterize how often specified events occur in the enrolled group, but it cannot by itself isolate the contribution of palbociclib from endocrine therapy, patient characteristics, or other influences. Any interpretation therefore needs to distinguish a descriptive treatment-group result from evidence of a comparative treatment effect.

4. Participant Flow and Accounting

The registry reports how participants moved through each stage of the study. All counts below are exactly as posted; missing counts are not inferred from other stages.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: The analysis population is comprised of all uncensored participants.

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.

6. Primary Endpoint

The registry lists the primary outcome as 2-Year Treatment Discontinuation Rate, measured over Evaluate upon completion of palbociclib, up to 2 years of treatment completion..

The primary endpoint is the 2-year treatment discontinuation rate, expressed as the percentage of participants who do not complete palbociclib treatment per protocol. The stated reasons are toxicity, withdrawal of consent to be treated, or other events related to tolerability. Participants who stop palbociclib early for reasons that are not treatment-related are censored. The analysis population is all uncensored participants, and the stated timeframe is evaluation upon completion of palbociclib, up to 2 years of treatment completion.

This endpoint is used to describe whether the combined regimen can be continued as intended over the specified treatment period. Discontinuation related to toxicity or tolerability is a practical feasibility outcome: it captures whether participants remain on the palbociclib component, rather than measuring tumor response or survival. The distinction between treatment-related and non-treatment-related stopping matters because the endpoint definition counts the former reasons and censors the latter. The registry record does not explain how these reasons were classified or adjudicated.

The endpoint specifies a 95% confidence interval, which would convey uncertainty around the estimated percentage. In general, a confidence interval gives a range of values compatible with the observed data under the analysis method; it does not eliminate uncertainty or establish that the estimate applies to other populations. The registry record does not report the primary endpoint estimate or its confidence interval. Therefore, the stated endpoint definition can be described, but the observed discontinuation rate and its precision cannot be assessed from the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The primary outcome is a binary participant-level event summarized as a percentage. A participant either meets the stated discontinuation definition or does not, within the endpoint’s analysis rules. The registry describes the outcome as a percentage of participants and specifies a 95% confidence interval. The posted record does not include the event count, the analysis denominator, the estimated percentage, or the interval itself. No recalculated estimate is therefore available for interpretation.

What does a confidence interval convey?

General explanation: A confidence interval describes statistical uncertainty around an estimate, conditional on the data and the method used to construct the interval. A narrower interval indicates greater precision under that method; a wider interval indicates less precision. The interval is not a guarantee that the true value lies within its endpoints, nor does it resolve design limitations such as the lack of a comparison group. Since the primary estimate and interval are not reported in the registry record, their width and the level of precision cannot be assessed for this endpoint.

Why does the analysis population matter?

The registry defines the endpoint population as all uncensored participants, rather than simply stating that every enrolled participant is included. It also specifies that participants who discontinue early for reasons unrelated to treatment are censored. This makes the endpoint’s interpretation depend on how censoring is applied and on which participants remain in the analysis population. The number of uncensored participants and the details for classifying discontinuation reasons are not reported in the registry record.

General explanation: Censoring means that a participant’s outcome is not counted as an observed event under the endpoint’s rules, often because the relevant event status or follow-up is not available in the required way. Censoring is not equivalent to observing that the event did not occur. If censoring is related to a participant’s likelihood of experiencing the event, the resulting estimate can be difficult to interpret. The registry record does not provide enough detail to assess the pattern of censoring or its assumptions in this study.

What can a single-group design estimate?

A single-group study can describe outcomes among participants receiving the regimen. It does not include a separate randomized control group, and allocation is listed as not applicable. The study also had no masking. These features mean there is no randomized between-group contrast in the registry record. A descriptive rate, if reported, would not by itself distinguish the effect of palbociclib from the effect of endocrine therapy or other factors associated with participants and care.

General explanation: Randomization can help balance measured and unmeasured factors between treatment groups, while a comparator supplies a reference for estimating a relative difference. Without those features, an observed event frequency is informative about the study group but is not a causal comparison. This does not make a descriptive study uninformative; it defines the kind of inference it can support.

How should the safety outcomes be distinguished?

The primary endpoint concerns stopping palbociclib for specified treatment-related or tolerability-related reasons. The secondary outcomes include grade 3-4 treatment-related neutropenia and all-grade treatment-related fatigue and alopecia. The registry’s serious adverse event count is a separate safety summary and is not interchangeable with the discontinuation endpoint or with those named secondary outcomes. Event severity, relationship to treatment, and whether an event led to discontinuation are distinct attributes.

The registry lists serious adverse event terms with percentages, but it does not report the results for the named secondary treatment-related outcomes. In general, an adverse-event percentage needs its event definition, analysis period, and denominator to be interpreted. A listed event term can also refer to participants who experienced that term; it should not be assumed to be a count of mutually exclusive participants across all terms. The record does not state whether the listed term categories overlap, so their percentages should not be combined.

What about sample-size planning?

The record includes general assumptions for a planning illustration: a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation, with an effect specified as a fraction of the observed effect. It distinguishes total events for time-to-event illustrations from participants per arm for other illustrations. Those assumptions are not a report of the trial’s own design justification. They also do not change the actual design, which is single group and has no randomized two-arm comparison. No sample-size illustration values are reported in the registry record.

General explanation: Planning calculations ask how many participants or events might be needed to detect a prespecified effect under stated assumptions. They are not observed trial outcomes, and they are not observed power. A planning illustration based on an observed effect is especially dependent on the chosen effect fraction and assumptions; it cannot establish what the trial was designed to detect unless the protocol’s design rationale is reported. The registry record does not report a protocol sample-size justification or the trial’s statistical plan.

Are interim analyses or multiplicity adjustments described?

The registry record does not report interim analyses, multiplicity adjustments, or a detailed analysis strategy for the primary and secondary outcomes. It names six outcome measures and lists one analysis, but it does not provide a multiplicity plan or clarify how the several outcomes were handled together. In general, examining multiple outcomes can increase the chance of at least one apparently notable result by chance when each is tested separately. Whether that issue is material depends on the planned analyses and interpretation, which are not described in the registry record.

Overall, the methods information supports a clear account of the endpoint definition and study structure, but not a reconstruction of the primary analysis. The estimate, interval, uncensored denominator, treatment of missing outcome information, and detailed statistical procedures are not reported in the registry record. Those omissions prevent evaluation of the numerical result and its precision, while the single-group design independently prevents a randomized comparative inference.

10. Exact Estimates for Each Arm

No two-arm comparison is shown for this trial, but each arm's result can still be summarized with exact interval estimates computed from the posted counts. The Clopper-Pearson interval is exact and conservative; the Wilson interval is a common closer-to-nominal alternative; the Bayesian credible interval uses a uniform Beta(1, 1) prior. For small groups the three can differ noticeably.

R code and output

arm    <- c("Palbociclib With Adjuvant Endocrine Therapy")
n      <- c(152)
events <- c(47)
for (i in seq_along(n)) {
  ci <- binom.test(events[i], n[i])$conf.int          # Clopper-Pearson exact interval
  cr <- qbeta(c(0.025, 0.975), 1 + events[i], 1 + n[i] - events[i])   # Bayesian, uniform Beta(1,1) prior
  wi <- (function(x, n) { p <- x / n; z <- qnorm(0.975); d <- 1 + z^2 / n
    c((p + z^2 / (2 * n) - z * sqrt(p * (1 - p) / n + z^2 / (4 * n^2))) / d, (p + z^2 / (2 * n) + z * sqrt(p * (1 - p) / n + z^2 / (4 * n^2))) / d) })(events[i], n[i])
  cat(sprintf("ARM|%s|%d|%d|%.1f|%.1f|%.1f|%.1f|%.1f|%.1f|%.1f\n", arm[i], n[i], events[i], 100 * events[i] / n[i],
              100 * ci[1], 100 * ci[2], 100 * wi[1], 100 * wi[2], 100 * cr[1], 100 * cr[2]))
}

ARM  Palbociclib With Adjuvant Endocrine Therapy  152  47  30.9  23.7  38.9  24.1  38.7  24.1  38.7

11. Multiplicity, Missing Data and Analysis Populations

The registry record lists six outcome measures. The named secondary outcomes include discontinuation by aromatase inhibitor and tamoxifen-based therapy subgroup, grade 3-4 treatment-related neutropenia, all-grade treatment-related fatigue, and all-grade treatment-related alopecia. The primary outcome is 2-year treatment discontinuation. The remaining outcome details, if distinct from these named measures, are not reported in the registry record.

The record does not report whether the analyses used a prespecified hierarchy, an adjustment for multiple testing, or another strategy for interpreting results across outcomes. It also does not report interim analyses or a detailed statistical analysis plan. In general, multiplicity refers to the increased chance of finding at least one apparently unusual result when several outcomes or comparisons are examined. Whether and how to address it depends on the planned questions and analysis; no adjustment should be assumed from the outcome list alone.

Missing-data information is limited. For the primary endpoint, participants who stopped early for reasons not related to treatment were censored, while the analysis population was all uncensored participants. The record does not report the number censored, the number included in the primary analysis, the amount of missing outcome information, or procedures for handling it. It also does not explain how treatment-related reasons for stopping were determined.

In general, an analysis population and missing-data rule affect the meaning of an estimate. Censoring can change which observed follow-up contributes to an estimate, and conclusions may depend on whether the reasons for censoring are related to the outcome. Without counts and further methodological detail, the direction or extent of any such influence cannot be assessed. The protocol’s sample-size justification, detailed analysis plan, and any sensitivity analyses are not reported in the registry record.

12. Safety Results

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

Deaths

Other (non-serious) adverse events

Participants with at least one non-serious event at or above the registry's 0% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: neutrophil count decreased (48.1%), fatigue (3.7%), cardiac disorders - other, specify (1.2%), mucositis oral (1.2%), breast infection (1.2%).

The registry lists 162 participants at risk for serious adverse events and 96 affected in the palbociclib with adjuvant endocrine therapy group. It reports 162 at risk and 162 affected for other adverse events, and 0 deaths. These are the posted safety counts; they are not results for the primary treatment-discontinuation endpoint. The record does not provide additional detail on the timing of each event or how individual events were linked to treatment discontinuation.

The listed serious adverse event terms include neutrophil count decreased at 48.1%, fatigue at 3.7%, cardiac disorders - Other, specify at 1.2%, mucositis oral at 1.2%, breast infection at 1.2%, and lymphocyte count decreased at 1.2%. These terms and percentages should be read as entries in the serious adverse event summary, not as a complete account of every safety outcome. The registry does not report whether participants could appear in multiple listed terms, so the percentages should not be added together.

Seriousness, severity grade, and treatment relationship are not interchangeable. The secondary outcome list separately identifies grade 3-4 treatment-related neutropenia and all-grade treatment-related fatigue and alopecia, but their results are not reported in the registry record. A serious adverse event term therefore should not automatically be interpreted as treatment-related, as a particular severity grade, or as an event that caused discontinuation. These safety counts describe what the registry reports, without establishing a causal explanation.

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

The study is a Phase 2 pilot feasibility evaluation of palbociclib combined with adjuvant endocrine therapy in hormone receptor positive invasive breast cancer. It enrolled 162 participants and used a single-group design. Its primary question concerns the 2-year rate of discontinuation for defined toxicity, consent, or tolerability reasons among uncensored participants. That endpoint is relevant to describing whether participants remain on the palbociclib component over the specified period.

The primary result itself is not reported in the registry record. Neither the discontinuation percentage nor its 95% confidence interval is available, and the number of uncensored participants is not reported. As a result, the record does not establish the observed frequency of the primary event or how precisely that frequency was estimated. The definition of an endpoint is not a substitute for its observed result.

The record does report selected safety counts: 96 participants affected by serious adverse events among 162 at risk, 162 affected by other adverse events among 162 at risk, and 0 deaths. It also lists serious adverse event terms and percentages. These figures can be described as registry-reported safety information, but they do not answer the primary endpoint question. They also do not establish that an event was caused by palbociclib, that it led to treatment discontinuation, or that the regimen changed the risk compared with an alternative.

Because the trial has no separate comparator group, its design cannot estimate a randomized difference between the combined regimen and another treatment. Even if the primary endpoint estimate were available, it would describe the study group under the endpoint’s rules; a comparative causal claim would require evidence the single-group design does not provide. The study also includes more than one endocrine therapy option, and the record does not report subgroup results for those choices.

Accordingly, the registry supports understanding the study’s treatment combination, design, endpoint definition, and selected adverse-event counts. It does not provide the numerical primary result, the named secondary outcome results, or a controlled comparison. These distinctions define what can and cannot be concluded from the record without turning a feasibility question into a claim about treatment benefit or harm.

14. Why This Trial Matters Statistically

This trial illustrates why statistical interpretation starts with the design and endpoint definition, not just an enrollment count or an adverse-event summary. A stated endpoint can be clinically and operationally meaningful while still being impossible to evaluate if its estimate, denominator, and confidence interval are not reported. Here, the endpoint targets treatment discontinuation under specific reasons and a defined analysis population, but the registry record does not provide the numerical result.

The censoring rule is another important statistical feature. Excluding or censoring participants for reasons classified as unrelated to treatment shapes the population to which the reported rate would apply. To assess the estimate, a reader would need the number of uncensored participants, the number meeting the endpoint, and enough detail about how stopping reasons were classified. Those details are not reported in the registry record.

The single-group design also clarifies the boundary between description and comparison. A study can report what happened to participants receiving the regimen, but without a control group it cannot separate the regimen’s contribution from other influences or provide a randomized estimate of a treatment contrast. This distinction matters when interpreting a feasibility outcome alongside safety summaries.

Finally, the record names multiple outcomes but does not describe how they were prioritized or how multiplicity was handled. In general, a clear analysis plan helps readers understand which results are confirmatory, how uncertainty is quantified, and how secondary findings should be interpreted. In this case, those methodological details are not reported. The example therefore highlights the value of complete outcome reporting and transparent definitions: they determine whether readers can assess not only what was measured, but also how much confidence to place in the resulting estimate.

15. 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 primary endpoint result is not reported in the registry record. The estimated 2-year treatment-discontinuation percentage, its 95% confidence interval, the event count, and the number of uncensored participants are all unavailable. This prevents assessment of the endpoint’s observed frequency and precision.

The design is single group, with no randomized allocation and no masking. There is no separate control arm for comparison. A result from this design would therefore describe outcomes in the enrolled group but could not establish a treatment difference against endocrine therapy alone or another regimen. The record also lists several endocrine therapy options without reporting how participants were distributed among them or giving subgroup results.

The endpoint uses censoring for early discontinuation judged unrelated to treatment, but the record does not report the number censored, the process for determining the reason, or the analysis details supporting that rule. Participant characteristics and further eligibility details are also not reported in the registry record, limiting assessment of how closely the study group represents other populations with the condition.

Although six outcome measures are listed, the record does not provide results for the named secondary outcomes or explain the analysis strategy across outcomes. Interim analyses, multiplicity handling, sensitivity analyses, and the trial’s sample-size justification are not reported. The generic planning assumptions do not replace a protocol-specific rationale or supply observed results. Finally, selected safety counts do not establish treatment causation and cannot fill the gap in the primary endpoint reporting.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Palbociclib in Combination With Adjuvant Endocrine Therapy for Hormone Receptor Positive, HER2 Negative Invasive Breast Cancer — NCT02040857.
• Registry record last updated 2025-04-29; status last verified 2025-04.
• Results first posted 2020-12-23.
• 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.

19. Record Summary

NCT02040857 is a completed Phase 2 pilot feasibility study sponsored by Dana-Farber Cancer Institute. It enrolled 162 participants and evaluated palbociclib combined with adjuvant endocrine therapy in hormone receptor positive invasive breast cancer. The registry lists a single-group design, no masking, a start date of 2014-01, and primary completion in 2018-05.

The primary endpoint is the 2-year treatment discontinuation rate among uncensored participants, with a 95% confidence interval specified. The discontinuation percentage and confidence interval are not reported in the registry record. Safety reporting lists 96 participants affected by serious adverse events among 162 at risk, 162 affected by other adverse events among 162 at risk, and 0 deaths. Named secondary outcome results and detailed statistical methods are not reported.