Study to Compare Alisertib With Paclitaxel vs. Paclitaxel Alone in Metastatic or Locally Recurrent Breast Cancer: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Study to Compare Alisertib With Paclitaxel vs. Paclitaxel Alone in Metastatic or Locally Recurrent Breast Cancer (NCT02187991), a randomized phase 2 study. The primary outcome is Time to Disease Progression - Tumor Response Based on RECIST 1.1 Criteria.

2. Clinical Question

3. Trial Design

This was a Phase II, multicenter, randomized, parallel-group study comparing alisertib plus paclitaxel with paclitaxel alone in metastatic or locally recurrent breast cancer. The registry lists the study as completed. The start date is 2015-02-12 and the primary completion date is 2024-04-11. The listed enrollment is 169.

Participants were assigned to treatment groups without masking. The four reported arms represent the combination and paclitaxel-alone regimens within the ER+/HER2- and triple-negative subgroups. The arm-specific time-to-progression results are reported separately: for ER+/HER2- disease, the paclitaxel-alone group had a median of 7.1 months, with bounds of 3.8 and 10.6, while the combination group had a median of 10.2 months, with bounds of 3.8 and 15.7. For triple-negative disease, the paclitaxel-alone group had a median of 5.7 months, with bounds of 2.9 and 8.2, while the combination group had a median of 9.6 months, with bounds of 6.1 and 22.6. The registry does not identify the statistical meaning of these lower and upper bounds in the posted arm entries.

The endpoint description distinguishes the analysis population from the safety population: all 174 participants who consented were included in the time-to-progression outcome analysis, while 5 did not start study treatment and 169 were included in the safety analysis. The reason for including participants who did not start treatment in the endpoint analysis, and the detailed handling of their follow-up, are not reported in the registry record. The randomization procedure, allocation concealment, and any stratification factors are also not reported in the registry record.

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: All 174 participants who consented were included in this Time to Disease Progression outcome analysis. However, 5 of these participants did not start study treatment, so only 169 participants were included in Safety Analysis.

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: 174 participants were consented and included in baseline analysis. However, 5 of these did not start study treatment due to ineligibility, participant withdrawal, and/or investigator decision, so only 169 participants were included in Participant Flow and Adverse Event/Serious Adverse Event (AE/SAE) Analysis.

6. Primary Endpoint

The registry lists the primary outcome as Time to Disease Progression - Tumor Response Based on RECIST 1.1 Criteria, measured over until disease progression (assessed by RECIST 1.1), unacceptable toxicity, death, or discontinuation from study for any other reason, up to 3 years from date of patient registration.

The primary endpoint was time to disease progression, measured in months and summarized by the median. The registry defines progression according to RECIST 1.1: a 20% increase in the sum of the longest diameters of target lesions, with an absolute increase of at least 5 mm; a measurable increase in a non-target lesion; or the appearance of new lesions. Tumors were measured every 8 weeks using CT/MRI and photographs, and bone scans were performed every 12 weeks if applicable.

The endpoint was followed until disease progression, unacceptable toxicity, death, or discontinuation from the study for another reason, up to 3 years from registration. In general, a time-to-event endpoint accounts for how long it takes for a specified event to occur and can use follow-up information from participants who have not experienced the event by the end of observation. The registry record does not report how such observations were handled, how censoring was defined, or which statistical method was used to estimate the medians.

The record labels the measure as a median with inter-quartile range as its dispersion. However, the posted arm results give lower and upper bounds without identifying those bounds as an inter-quartile range or specifying another interpretation. They should therefore not be assigned a confidence level or treated as a particular uncertainty interval based on the registry record alone.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The primary result is a time-to-event summary. The registry reports a median for each arm and labels the dispersion as an inter-quartile range. It does not include an inferential estimate comparing the randomized groups. As a result, the posted values support a descriptive reading of the observed arm summaries but not a formal conclusion about the comparative effect.

What does a median time-to-event result describe?

In general, the median is the time by which half of the relevant population is estimated to have experienced the event, using the method applied to the follow-up data. Here, the event is disease progression under RECIST 1.1. A median condenses the timing information into a central summary; it does not show the full distribution of times or the proportion experiencing progression at every point in follow-up. The registry does not provide survival curves or enough methodological detail to reconstruct the estimation procedure.

How should the arm bounds be read?

The registry identifies inter-quartile range as the dispersion measure for the primary outcome, while the posted results display a lower and upper bound for each arm. The record does not explicitly identify those bounds as the inter-quartile range, confidence limits, or another interval. In general, an interval can communicate variation or uncertainty, but its meaning depends on how it was calculated. It is not appropriate to interpret these bounds as a confidence interval for the treatment contrast or to infer a confidence level that the record does not state.

In general, confidence intervals for a between-group effect describe the range of effect estimates compatible with the data and the specified statistical model. Such an interval is different from bounds around a single arm’s median. Because no comparative interval is posted, the precision of the difference between the treatment groups cannot be assessed from the reported arm summaries.

What does randomization contribute?

In general, random allocation is intended to make treatment groups comparable in expectation, reducing the risk that treatment choice is systematically tied to participant characteristics. This design is described as randomized, parallel-group, and unmasked. The method for generating and concealing the allocation is not reported in the registry record. No masking also means the registry does not describe a blinded treatment assignment. How that feature affected assessment or conduct is not reported.

Why does the subgroup structure matter?

The results are listed separately for ER+/HER2- and triple-negative disease. Each subgroup has its own pair of treatment arms and its own reported medians. These results should not be combined informally: a pooled estimate would require a specified method and appropriate data, neither of which is reported. The record also does not provide a formal test of whether the treatment contrast differs by subgroup. In general, subgroup comparisons can be less precise when the groups contain fewer participants, and results across subgroups can vary by chance.

What can be learned from the planning illustration?

The planning illustration is based on the observed effect, not on the trial’s documented design. Its stated assumptions are a two-sided significance level of 0.05, equal allocation between the two arms, and a normal approximation; the effect to detect is defined as a stated fraction of the observed effect. In general, a planning calculation estimates the sample size needed under specified assumptions. It is not an estimate of the probability that this completed study detected an effect, and it does not show observed power. The record does not report the original sample-size justification, the effect size used when planning the trial, or whether this illustration corresponds to the trial’s actual design.

The registry reports no posted analyses for the primary outcome. It also does not provide the sponsor’s hazard-ratio analysis or other comparative model output. Accordingly, no hazard ratio, test statistic, or statistical significance claim can be reconstructed from the median values and their bounds alone.

10. Multiplicity, Missing Data and Analysis Populations

The registry lists Overall Survival as a secondary outcome and reports two outcome measures, but detailed secondary-outcome results are not included in the posted information described for this analysis. The number of posted analyses is 0. The registry record does not report a multiplicity adjustment, a hierarchy of hypotheses, or a prespecified strategy for interpreting multiple outcomes or subgroup comparisons. Without those details, it is not possible to assess how the primary endpoint relates to other planned statistical tests.

The endpoint population is described as all 174 participants who consented, including 5 who did not start study treatment. The safety analysis includes 169 participants. The reasons those participants did not start treatment, their endpoint follow-up, and the handling of missing outcome data are not reported in the registry record. The record also does not state whether the primary analysis followed an intention-to-treat principle, a modified intention-to-treat principle, or another population definition.

In general, missing-data methods can affect time-to-event estimates when event status or follow-up is unavailable. The registry does not report the amount or pattern of missing primary endpoint data, the censoring rules, or any sensitivity analyses. The reason for the difference between the consented endpoint population and the safety population is partly described as treatment not being started, but the full participant disposition and analysis rules are not reported.

The record does not report interim analyses, stopping rules, or a protocol-based sample-size justification. Those details should not be inferred from the planning illustration, which is explicitly based on the observed effect rather than the trial’s own documented design.

11. 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 2% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: febrile neutropenia (11.1%), sepsis (11.1%), diarrhea (5.6%), infection fungal (5.6%), neutropenia (3.0%).

The safety results give the number of participants reported as affected by serious adverse events alongside the number at risk in each group. For ER+/HER2- participants, serious adverse events affected 2 of 70 in the paclitaxel-alone group and 13 of 66 in the combination group. For triple-negative participants, the corresponding counts were 0 of 15 and 6 of 18. The registry also reports other adverse events affecting 69 of 70, 65 of 66, 15 of 15, and 18 of 18 participants in the listed groups, respectively.

These counts are descriptive. The registry does not provide a comparative statistical analysis of the safety outcomes, and the group denominators for these safety results differ from some of the arm sizes reported for the primary endpoint. The record does not specify whether adverse-event counts reflect unique participants, event episodes, or a particular coding and attribution rule; the figures should be interpreted according to the registry’s participant-affected wording rather than treated as event totals.

The listed serious adverse event terms include FEBRILE NEUTROPENIA and SEPSIS at 11.1% each, DIARRHEA and INFECTION FUNGAL at 5.6% each, NEUTROPENIA at 3.0%, and NAUSEA at 1.5%. The registry does not assign these term percentages to a particular treatment group in the information.

Deaths are listed as 43, 39, 14, and 13 for the corresponding groups. The registry does not identify these death counts as deaths caused by treatment or provide a comparative analysis of mortality. They should not be interpreted as treatment-related deaths without that information.

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

The registry reports arm-specific median times to disease progression for alisertib plus paclitaxel and paclitaxel alone in ER+/HER2- and triple-negative disease. In each subgroup, the posted median is numerically higher for the combination group. This is a description of the reported summaries, not a conclusion that the combination caused a longer time to progression.

The record does not include a sponsor-reported hazard ratio, a comparative confidence interval, a p-value, or another inferential result for the primary endpoint. It also does not identify the statistical meaning of the lower and upper bounds accompanying the medians. Therefore, the precision of the treatment contrast and the strength of evidence for a difference cannot be established from the posted results alone.

In general, a randomized comparison can support causal interpretation when the allocation process is sound and the analysis appropriately accounts for follow-up, missingness, and the planned population. The registry confirms randomization but does not report the allocation procedure or important analysis details. The absence of those details in the record limits what can be evaluated; it does not establish that the methods were or were not appropriate.

The results also do not establish that the two disease subgroups have the same or different treatment effects. Separate subgroup medians are not a formal test of interaction. The record does not report a subgroup-comparison model or an interaction result. Nor do the time-to-progression values alone describe safety, overall survival, symptoms, or quality of life.

The serious adverse event and death counts provide additional descriptive information but are not accompanied by a formal comparison. Taken together, the registry supports a careful account of reported arm outcomes, while leaving substantial uncertainty about comparative effects, their precision, and how they relate to safety. No treatment recommendation follows from these registry summaries.

13. Why This Trial Matters Statistically

This trial raises familiar statistical issues in randomized oncology studies: time-to-event outcomes, subgroup-specific reporting, and the distinction between descriptive arm summaries and comparative estimates. The median time to progression is clinically interpretable as a summary of event timing, but the comparative question requires an effect estimate and information about its uncertainty. Those comparative statistics are not reported in the registry record.

The separate ER+/HER2- and triple-negative results make the target of interpretation important. Each subgroup has its own pair of arms, and the number of participants reported in the triple-negative arms is smaller than in the ER+/HER2- arms. In general, smaller groups tend to yield less precise estimates, and subgroup findings should be interpreted with attention to uncertainty and any prespecified analysis plan. The registry does not report an interaction analysis or multiplicity strategy.

The endpoint population also highlights the need to distinguish consent, treatment initiation, and analysis inclusion. The record says that all 174 participants who consented were included in the primary outcome analysis, while 5 did not start treatment and 169 were included in safety analysis. These statements make the population definitions visible, but the detailed handling of follow-up and missing data is not reported.

Finally, the safety results illustrate why counts and percentages need context. Serious adverse events, other adverse events, and deaths are reported with group-specific denominators or counts, but the record does not provide comparative tests or a formal benefit-risk analysis. Statistical interpretation depends not only on the displayed values but also on transparent definitions, analysis methods, and uncertainty estimates.

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 registry gives median time-to-progression results by arm but does not report a sponsor hazard ratio, a comparative confidence interval, a p-value, event counts for the primary endpoint, or a statistical model. It therefore does not show the magnitude and precision of the randomized treatment contrast in a form that can be evaluated directly. The lower and upper bounds accompanying each median are not identified as a particular type of interval, despite the endpoint description naming inter-quartile range as the dispersion measure.

Important design and analysis details are not reported in the registry record. These include the randomization sequence and concealment methods, the analysis population definition, censoring rules, missing-data methods, and any sensitivity analyses. The record does not report an interaction test for the ER+/HER2- and triple-negative subgroups, or a multiplicity plan for the primary and secondary outcomes.

The primary endpoint description includes all 174 participants who consented, while the safety analysis includes 169 and notes that 5 did not start treatment. The record does not detail the follow-up or endpoint data for participants who did not start treatment. The safety denominators also differ across the reported groups and outcome descriptions, and no explanation for those differences is included.

The safety information is descriptive and does not give a formal comparative analysis. The listed serious adverse event terms are not assigned to treatment groups in the reported information, and the deaths are not identified as treatment-related. Overall Survival is listed as a secondary outcome, but its results are not included in the posted information. The original sample-size rationale, interim analyses, and stopping rules are also not reported in the registry record.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Study to Compare Alisertib With Paclitaxel vs. Paclitaxel Alone in Metastatic or Locally Recurrent Breast Cancer — NCT02187991.
• Registry record last updated 2024-10-09; status last verified 2024-09.
• Results first posted 2024-10-09.
• Data retrieved from ClinicalTrials.gov on 2026-11-09.
• Group sizes, means, event counts and sponsor-reported p-values are reproduced as posted. Effect estimates, confidence intervals and p-values not attributed to the sponsor are independently calculated from the posted summary statistics.

18. Record Summary

NCT02187991 is a completed Phase II, multicenter, randomized, parallel-group study sponsored by US Oncology Research. It compared alisertib plus paclitaxel with paclitaxel alone in metastatic or locally recurrent breast cancer, reporting separate arms for ER+/HER2- and triple-negative disease. Masking is listed as none.

The primary outcome was time to disease progression assessed by RECIST 1.1, summarized as a median in months. The record reports arm medians and lower and upper bounds, but does not identify the statistical meaning of those bounds or provide a comparative hazard ratio or inferential test. It describes 174 consented participants in the endpoint analysis, including 5 who did not start treatment, and 169 participants in the safety analysis.

Overall Survival is listed as a secondary outcome. Serious adverse events, other adverse events, and deaths are reported descriptively by group. Detailed comparative analyses, missing-data methods, multiplicity procedures, and the original sample-size justification are not reported in the registry record.