This page provides an independent statistical analysis and educational interpretation of publicly reported results. ClinicalTrials.gov provides the official trial registry record.
1. Trial at a Glance
PALLAS is a randomized, parallel-group phase 3 treatment trial in breast cancer. The registered primary endpoint is invasive disease-free survival (iDFS) at 4 years, a time-to-event endpoint comparing palbociclib plus endocrine therapy with endocrine therapy alone.
| Feature | PALLAS |
|---|---|
| Trial name | PALLAS — PALbociclib CoLlaborative Adjuvant Study |
| Phase | Phase 3 |
| Condition | Breast Cancer |
| Population | Patients with histologically confirmed HR+/HER2- invasive early breast cancer |
| Design | Randomized, parallel-group |
| Masking | None |
| Primary purpose | Treatment |
| Enrollment | 5796.0 |
| Primary endpoint | Invasive Disease Free Survival (iDFS) at 4 years |
| Primary endpoint type | Time-to-event |
| Registered statistical method | Log-rank test |
| Effect measure | Hazard ratio |
| ClinicalTrials.gov | NCT02513394 |
| Status | ACTIVE_NOT_RECRUITING |
| Start | 2015-08 |
| Primary completion | 2020-11 |
2. Clinical Question
The central statistical question is whether adding 2 years of palbociclib to a planned course of at least 5 years of endocrine therapy changes invasive disease-free survival at 4 years compared with at least 5 years of endocrine therapy alone.
Population
Patients with histologically confirmed HR+/HER2- invasive early breast cancer.
Intervention
Palbociclib plus standard adjuvant endocrine therapy, with the registered endpoint describing 2-year palbociclib treatment and at least 5 years of endocrine therapy.
Comparator
Standard adjuvant endocrine therapy alone, with the registered endpoint describing at least 5 years of endocrine therapy.
Primary question
Does the randomized treatment comparison produce a different time-to-invasive-disease-event profile at 4 years?
3. Trial Design
Palbociclib Plus Endocrine Therapy
- Palbociclib
- Standard adjuvant endocrine therapy
- The registered primary endpoint describes 2-year palbociclib treatment with at least 5 years of endocrine therapy.
Endocrine Therapy Alone
- Standard adjuvant endocrine therapy
- The registered primary endpoint describes at least 5 years of endocrine therapy.
4. Primary Endpoint
| Endpoint | Registered definition / frame | Endpoint type |
|---|---|---|
| Invasive Disease Free Survival (iDFS) | Invasive disease-free survival (iDFS) for the combination of at least 5 years endocrine therapy and 2-year palbociclib treatment versus at least 5 years endocrine therapy alone in patients with histologically confirmed HR+/HER2- invasive early breast cancer (EBC) at 4 years. iDFS is defined as the time from randomization to the date of the first event: local/regional invasive ipsilateral recurrence, contralateral invasive breast cancer, distant recurrence, second primary invasive cancer of non-breast origin or death from any cause. Direct comparison between arms used time to iDFS events and Kaplan-Meier Log-rank analysis. Due to the medians not yet achieved, the percentage of patients considered iDFS at 4 years is reported. | Time-to-event |
The registry definition is the controlling description for this page. The ClinicalTrials.gov record ends the definition at “local/regional invasive ipsilateral recurrence, contralateral invasive breast cancer, distant recurrence, second primary invasive cancer of non-breast origin or death from any cause. Direct comparison between arms used time to iDFS events and Kaplan-Meier Log-rank analysis. Due to the medians not yet achieved, the percentage of patients considered iDFS at 4 years is reported.,” so this analysis does not extend or reconstruct the remainder of the event definition.
5. Primary Results: Invasive Disease-Free Survival
The ClinicalTrials.gov results contain a formal statistical analysis for the primary endpoint. The comparison is between palbociclib plus endocrine therapy and endocrine therapy alone at 4 years.
Hazard ratio for invasive disease-free survival
95% CI: 0.81–1.14 · P = 0.65
Two-sided log-rank analysis; the reported analysis was stratified by (neo)adjuvant chemotherapy (yes vs no) and age (≤50 vs >50).
| Primary endpoint | Comparison | Method | HR | 95% CI | P-value |
|---|---|---|---|---|---|
| Invasive Disease Free Survival (iDFS), 4 years | Palbociclib + endocrine therapy vs endocrine therapy alone | Log Rank | 0.96 | 0.81–1.14 | 0.65 |
The hazard ratio of 0.96 is a relative time-to-event measure comparing the estimated instantaneous event rates between the two randomized groups under the analysis framework. An HR of 0.96 corresponds to an estimated hazard approximately 4% lower in Arm A than Arm B; this is a model-based relative comparison, not a statement that 4% of patients avoided an event.
The 95% confidence interval of 0.81–1.14 describes uncertainty around the estimated hazard ratio. Because the interval spans 1, the data are compatible with both a lower and a higher estimated hazard under the model. The interval does not describe the range of effects experienced by individual patients.
The P-value of 0.65 is a measure of compatibility between the observed data and the statistical testing framework; it is not a measure of the size or clinical importance of the treatment effect. A p-value should therefore not be read as a probability that the treatment works or does not work.
The registry specifies a two-sided analysis and states that the p-value was stratified by (neo)adjuvant chemotherapy and age. Because iDFS is a time-to-event endpoint, interpretation also depends on the event and censoring rules defined for the endpoint. The ClinicalTrials.gov record does not provide a proportional-hazards diagnostic, so the hazard-ratio summary should not be interpreted as proving that proportional hazards held throughout follow-up.
For this trial, the reported HR of 0.96 compares palbociclib plus endocrine therapy with endocrine therapy alone. The hazard ratio is not an absolute risk difference, a risk ratio, or a percentage of patients benefiting.
6. Secondary Time-to-Event Results
The registry contains four secondary time-to-event outcome analyses with hazard-ratio estimates and 95% confidence intervals. The ClinicalTrials.gov record does not report a formal statistical method or p-value for these secondary analyses.
| Secondary endpoint | Time frame | HR | 95% CI | Method in the ClinicalTrials.gov record |
|---|---|---|---|---|
| Invasive Disease Free Survival (iDFS) Excluding Second Primary Invasive Cancers of Non-breast Origin. | 4 years | 0.99 | 0.82–1.19 | Not reported |
| Distant Recurrence-free Survival (DRFS) | 4 years | 1.05 | 0.87–1.28 | Not reported |
| Overall Survival (OS) | 4 years | 1.32 | 0.98–1.78 | Not reported |
| Locoregional Recurrences-free Survival (LRRFS) | 4 years | 0.84 | 0.57–1.23 | Not reported |
How to read these estimates
All four secondary endpoints are time-to-event measures, and the reported effect measure is the hazard ratio. An HR below 1 describes a lower estimated instantaneous event rate in the palbociclib-plus-endocrine-therapy group; an HR above 1 describes a higher estimated instantaneous event rate under the same comparison direction.
The confidence intervals show why the point estimate alone should not be treated as the complete result. For example, the DRFS estimate is 1.05 with a 95% CI of 0.87–1.28. The interval spans 1, so the ClinicalTrials.gov record does not establish a direction of effect with high precision. Likewise, the OS estimate of 1.32 has a 95% CI of 0.98–1.78, which also spans 1.
7. Statistical Methodology
Log-rank test
The primary analysis uses a log-rank test, a standard method for comparing time-to-event distributions between randomized groups. Rather than reducing follow-up to a single event/no-event indicator, the log-rank framework uses the ordering of event times and the numbers at risk over follow-up.
The log-rank test evaluates whether the observed pattern of events over time differs between the treatment groups under its testing framework.
Hazard ratio
The primary result is reported as a hazard ratio. This provides a relative comparison of the estimated instantaneous event rates between the two treatment groups. It is especially useful for summarizing a time-to-event comparison, but it does not directly give an absolute probability of being event-free at a specified time.
The derived “4%” is simply 1 − 0.96. It should not be interpreted as a 4-percentage-point difference in 4-year iDFS, nor as a 4% absolute reduction in the number of patients experiencing an event.
Stratified analysis
The primary analysis notes that its two-sided p-value was stratified by (neo)adjuvant chemotherapy (yes vs no) and age (≤50 vs >50). Stratification allows the comparison to account for these specified factors rather than treating every patient as belonging to one undifferentiated risk set.
Conceptually, stratification asks whether the treatment comparison is consistent after organizing the risk sets according to prespecified characteristics. It does not mean that separate treatment effects must be estimated for every stratum.
Kaplan-Meier estimation
Kaplan-Meier estimation is the natural descriptive companion to a time-to-event endpoint such as iDFS. It estimates the probability of remaining event-free over time while accommodating right-censored observations.
Here, di represents events at an event time and ni represents participants at risk immediately before that time. The registry-reported PALLAS data do not provide the underlying event and censoring records needed to reconstruct a trial-specific curve.
Censoring and follow-up
Time-to-event analyses can use information from participants who have not yet experienced the endpoint, provided their follow-up remains available. Such observations are censored according to the applicable endpoint rules. Correct censoring is important because incorrectly treating a censored participant as an event, or vice versa, can change the estimated survival experience.
Analysis population and randomization
The ClinicalTrials.gov record identifies the trial allocation as randomized but do not provide a separate analysis-population definition such as an explicit intention-to-treat or as-treated rule. Accordingly, this page does not assign an analysis population beyond what is explicitly contained in the ClinicalTrials.gov record.
8. Statistical Methods Explained
Why was a log-rank test used?
The primary endpoint is a time-to-event outcome. A log-rank test is designed for comparing event-time distributions between groups while accounting for the timing of events and censoring. This is more informative for a time-to-event endpoint than simply comparing the proportion of participants with an event at one arbitrary follow-up point.
What does an HR of 0.96 mean?
An HR of 0.96 means the estimated instantaneous event rate in the palbociclib-plus-endocrine-therapy group was approximately 96% of that in the endocrine-therapy-alone group under the reported analysis. Equivalently, it is approximately a 4% lower estimated hazard. It does not mean that 4% fewer patients had an event, and it does not imply an identical effect for every participant.
Why is the confidence interval important?
The point estimate is only one summary of the treatment comparison. The 95% CI of 0.81–1.14 gives a range describing uncertainty around the estimated hazard ratio. An interval that spans 1 indicates that the data are compatible with hazard ratios on either side of the no-difference value under the specified statistical framework.
What does the P-value of 0.65 tell us?
The p-value summarizes the degree of compatibility between the observed data and the null hypothesis within the testing framework. It does not quantify the size of the treatment effect, the probability that the null hypothesis is true, or the probability that a treatment is ineffective.
Why was the analysis stratified?
The primary analysis states that its two-sided p-value was stratified by (neo)adjuvant chemotherapy and age. Stratification can improve alignment between the statistical comparison and the structure of the randomized design by accounting for specified prognostic or design factors within the comparison.
Why does time-to-event analysis need censoring?
Not every participant necessarily experiences an endpoint during the period in which they are observed. A censored participant still contributes information up to the censoring time. Kaplan-Meier and log-rank methods are built to use that partial follow-up rather than discarding the participant entirely.
9. What the Primary Result Does — and Does Not — Mean
The primary hazard ratio of 0.96 is a relative estimate comparing the instantaneous event rates for iDFS between the two randomized groups. The estimate is close to the no-difference value of 1, and its 95% CI of 0.81–1.14 includes 1.
This does not mean that 96% of patients remained disease-free, that 4% of patients benefited, or that the treatment changed absolute 4-year iDFS by 4 percentage points. None of those quantities is represented by the hazard ratio.
The 95% CI of 0.81–1.14 conveys statistical precision around the reported point estimate. Its width indicates that the point estimate should not be interpreted as an exact treatment effect. The interval also includes the null value of 1.
The reported P = 0.65 is associated with the two-sided primary test. A p-value does not tell us how large the treatment effect is. Effect magnitude and uncertainty are better conveyed by the hazard ratio together with its confidence interval.
A hazard ratio and a time-specific percentage answer different statistical questions. The registry-reported PALLAS data provide a hazard ratio for the primary endpoint but do not provide the underlying 4-year iDFS percentages needed for an absolute-risk presentation.
10. Safety Results
The ClinicalTrials.gov record provides serious adverse-event counts by randomized arm as affected participants divided by participants at risk. No additional safety categories are contained in the ClinicalTrials.gov record.
| Safety measure | Arm | Affected / at risk |
|---|---|---|
| Serious adverse events | Palbociclib Plus Endocrine Therapy (Arm A) | 369/2841 |
| Serious adverse events | Endocrine Therapy Alone (Arm B) | 229/2902 |
These figures should be interpreted as a safety summary rather than as a time-to-event efficacy result. The ClinicalTrials.gov record does not provide a statistical comparison, confidence interval, p-value, severity breakdown, or exposure-adjusted analysis for serious adverse events.
11. Multiplicity and Secondary Endpoints
The registry identifies one registered primary endpoint and four additional posted outcome analyses. The primary endpoint is iDFS at 4 years. The four secondary outcomes are additional time-to-event measures at 4 years.
| Endpoint | Role | Statistical result reported |
|---|---|---|
| Invasive Disease Free Survival (iDFS) | Primary | HR 0.96; 95% CI 0.81–1.14; P = 0.65 |
| iDFS excluding second primary invasive cancers of non-breast origin | Secondary | HR 0.99; 95% CI 0.82–1.19 |
| Distant Recurrence-free Survival (DRFS) | Secondary | HR 1.05; 95% CI 0.87–1.28 |
| Overall Survival (OS) | Secondary | HR 1.32; 95% CI 0.98–1.78 |
| Locoregional Recurrences-free Survival (LRRFS) | Secondary | HR 0.84; 95% CI 0.57–1.23 |
The ClinicalTrials.gov record does not state a multiplicity-adjustment procedure, hierarchical testing strategy, alpha allocation, or multiplicity-adjusted p-values for the secondary endpoints. Those features therefore should not be inferred from the presence of multiple posted outcomes.
12. Stratification and the Meaning of the Primary Test
The primary analysis specifically states that the two-sided p-value was stratified by (neo)adjuvant chemotherapy (yes vs no) and age (≤50 vs >50). This is an important detail because the reported p-value is not described as coming from an unstratified comparison.
Stratification factor
(Neo)adjuvant chemotherapy: yes vs no.
Age factor
≤50 vs >50.
Test direction
The registry reports a two-sided p-value.
Reported test
Log Rank for the primary iDFS analysis.
Stratification does not change the randomized treatment assignment. Instead, it changes how the treatment comparison is evaluated across the specified strata. This can be particularly useful when a prognostic factor affects event timing.
13. Limitations and Interpretation Issues
- Incomplete endpoint definition in the ClinicalTrials.gov record: the registry-reported iDFS definition ends at “local/regional invasive ipsilateral recurrence, contralateral invasive breast cancer, distant recurrence, second primary invasive cancer of non-breast origin or death from any cause. Direct comparison between arms used time to iDFS events and Kaplan-Meier Log-rank analysis. Due to the medians not yet achieved, the percentage of patients considered iDFS at 4 years is reported.,” so this page does not reconstruct the remainder of the registry endpoint definition.
- Limited methodological detail for secondary analyses: the ClinicalTrials.gov record provides hazard ratios and confidence intervals for four secondary endpoints but identify their methods as “Not reported.”
- No absolute 4-year iDFS values reported: the primary result is reported as a hazard ratio with a confidence interval and p-value, without corresponding time-specific event-free percentages in the ClinicalTrials.gov record.
- No Kaplan-Meier data reported: the underlying event and censoring records are not provided, so a trial-specific Kaplan-Meier curve cannot be reconstructed from the registry-reported summary statistics.
- No proportional-hazards assessment reported: the data identify a hazard ratio but do not report diagnostics or tests concerning the proportional-hazards assumption.
- No multiplicity strategy reported: the data do not specify an alpha-allocation or multiplicity-adjustment procedure for the secondary endpoints.
- No analysis-population definition reported: the registry data identify randomized allocation but do not provide a detailed efficacy analysis-population rule in the registry-reported material.
- Safety information is limited: only serious adverse events by arm are reported; no formal statistical comparison or broader safety profile is available in the ClinicalTrials.gov record.
14. Why This Trial Matters Statistically
PALLAS is useful for learning how a large randomized trial can be reduced to a precise time-to-event question. The primary endpoint is not simply whether an event occurred; it is invasive disease-free survival measured from randomization. That structure naturally leads to survival-analysis methods such as the log-rank test and hazard ratios.
The primary result also illustrates why statistical interpretation should not stop at a p-value. The reported HR of 0.96, 95% CI of 0.81–1.14, and P = 0.65 tell different parts of the statistical story. The HR describes the estimated relative event rate, the confidence interval describes uncertainty around that estimate, and the p-value describes evidence within the specified testing framework.
The stratified nature of the primary analysis provides another important lesson. The reported p-value was stratified by (neo)adjuvant chemotherapy and age, showing that the treatment comparison was not evaluated as a completely unstructured pooled comparison.
Finally, the four secondary endpoints demonstrate why a trial's statistical hierarchy matters. Multiple time-to-event outcomes can provide different perspectives on disease recurrence and survival, but their estimates should not automatically be treated as independent confirmatory conclusions when the ClinicalTrials.gov record does not specify the multiplicity framework.
15. A Practical Statistical Reading of PALLAS
| Question | What the ClinicalTrials.gov record shows | How to interpret it |
|---|---|---|
| What was the primary endpoint? | iDFS at 4 years | A time-to-event endpoint comparing the randomized treatment groups. |
| What was the primary method? | Log Rank | A survival-analysis method for comparing event-time distributions. |
| What was the effect measure? | HR 0.96 | A relative measure of estimated instantaneous event rates. |
| How precise was the estimate? | 95% CI 0.81–1.14 | The interval includes the no-difference value of 1. |
| What was the reported p-value? | 0.65 | A two-sided p-value from the stratified primary analysis. |
| Which factors were used for stratification? | (Neo)adjuvant chemotherapy and age | The p-value was stratified by these specified categories. |
16. Longitudinal Trial Context
Trial start
2015-08
Primary completion
2020-11
Current registry status
ACTIVE_NOT_RECRUITING
Lead sponsor
Alliance Foundation Trials, LLC.
The registry identifies PALLAS as a phase 3 randomized treatment study with 5796.0 participants enrolled. The ClinicalTrials.gov record establishes the trial's start and primary-completion dates, but do not provide a detailed sequence of interim analyses, protocol amendments, data cutoffs, or later statistical updates.
17. Sources
The statistical content on this page is based on the ClinicalTrials.gov record. The following links are the registry and PubMed records identified in that source material.
- ClinicalTrials.gov — PALLAS, NCT02513394
- PubMed record — PMID 40140172
- PubMed record — PMID 39849600
- PubMed record — PMID 37556775
- PubMed record — PMID 34995105
- PubMed record — PMID 34874182