Trial Evaluating Dovitinib Combined With Fulvestrant, in Postmenopausal Patients With HER2- and HR+ Breast Cancer: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Trial Evaluating Dovitinib Combined With Fulvestrant, in Postmenopausal Patients With HER2- and HR+ Breast Cancer (NCT01528345), a randomized phase 2 study. The primary outcome is Progression Free Survival (PFS) Based on Local Investigator Assessment.

2. Clinical Question

The comparison is between two regimens that share fulvestrant; the randomized contrast concerns adding active dovitinib rather than its matching placebo. The registered primary endpoint is progression-free survival (PFS), measured from randomization until radiologically documented disease progression or death due to any cause. Local investigators assessed the endpoint using RECIST v1.1.

The registry describes a population with disease progression on or after endocrine therapy, and the brief summary also specifies locally advanced or metastatic disease not amenable to curative surgery or radiotherapy. These criteria define the clinical setting represented in the trial record. They do not establish that every patient meeting those broad descriptions would have been eligible; the full eligibility criteria are not reported in the registry record.

The central statistical question is whether the observed time-to-event experience differed between the assigned groups, and how precisely any reported contrast estimates that difference. In this record, the primary endpoint is named, but no group-specific median, confidence interval, or hazard ratio is available. Consequently, the direction, magnitude, and precision of the primary comparison cannot be described from the registry record.

3. Trial Design

The registry identifies this as a phase II, randomized, double-blind, placebo-controlled trial. It records enrollment of 97 participants and lists a terminated status. The registry record does not report the reason for termination, so the status alone cannot establish why recruitment or follow-up ended, or whether termination was related to safety, efficacy, feasibility, or another consideration.

The two described groups received fulvestrant with either active dovitinib or a matching dovitinib placebo. This design aims to isolate the contrast associated with assignment to active dovitinib while keeping the listed background treatment the same. Double masking is recorded, but the registry record does not report who was masked or describe procedures for maintaining masking.

There is an internal design-label ambiguity: allocation is recorded as randomized and two treatment groups are described, while the model is separately labeled single-group. The record does not explain this discrepancy. The randomized, two-arm descriptions support describing the intended comparison, but the single-group label should remain visible as a registry inconsistency rather than being silently resolved.

The primary outcome was PFS based on local investigator assessment, with assessments scheduled every 8 weeks and follow-up specified up to 34 months. The listed secondary outcomes include overall response rate, duration of response, overall survival using the Kaplan-Meier method, adverse events as a safety measure, and time to worsening of ECOG performance status. The registry lists six outcome measures overall; the individual outcome entries and reported results are not all available in this record.

Start is recorded as 2012-04 and primary completion as 2015-04. These entries provide registry timing, not a detailed account of recruitment or follow-up. The record does not report the planned sample-size justification, allocation ratio, stratification factors, or a full statistical analysis plan.

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: Full Analysis Set (FAS): Consisted of all randomized patients. Following the intent-to-treat principle, patients were analyzed according to the treatment and stratum to which they wereassigned at randomization.

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: Full Analysis Set (FAS): Consisted of all randomized patients. Following the intent-to-treat principle, patients were analyzed according to the treatment and stratum to which they were assigned at randomization.

6. Primary Endpoint

The registry lists the primary outcome as Progression Free Survival (PFS) Based on Local Investigator Assessment, measured over Every 8 weeks assessed up to 34 months.

The primary endpoint is median PFS based on local investigator assessment. PFS is defined as time from randomization to the first radiologically documented disease progression or death due to any cause. Counting death as an event means that the endpoint incorporates both documented progression and death, rather than treating progression alone as the event.

Assessments were scheduled every 8 weeks, up to 34 months. The endpoint uses RECIST v1.1 response categories. The description defines complete response as disappearance of all non-nodal target lesions and partial response as at least a 30% decrease in the sum of target-lesion diameters from baseline. Progressive disease is defined as at least a 20% increase from the smallest sum recorded at or after baseline. Stable disease meets neither the response nor progression threshold. An unknown assessment is one where progression is not documented and one or more target lesions have not been assessed, or were assessed using a different method than at baseline.

Time-to-event endpoints are useful when the timing of an event matters and participants may have different lengths of observation. A median describes the time by which half of the estimated event-time distribution has experienced the event, subject to the analysis method and censoring. A confidence interval expresses uncertainty around the estimated median; it is not a guarantee that an individual’s outcome will fall within that interval.

The registry record names median PFS and a 95% confidence interval as the measure, but it does not report either group’s median or confidence interval. It therefore permits explanation of the endpoint definition, but not a numerical comparison of PFS between groups.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The main statistical features are a randomized two-group comparison, a time-to-event primary endpoint, and a stated analysis population. The registry record provides the endpoint definition and selected safety counts, but does not report the numerical primary results or a complete analysis plan. The concepts below explain how such methods are generally interpreted; they do not describe unreported procedures as if they were used in this trial.

What does randomization contribute?

In general, randomization assigns participants to groups using a chance-based procedure. Its purpose is to make treatment assignment independent of measured and unmeasured prognostic factors in expectation. This supports a causal comparison of assigned strategies when the trial is conducted and analyzed appropriately. Randomization does not ensure that the groups will have identical baseline characteristics, and it does not eliminate uncertainty. The registry identifies this study as randomized and describes two groups, but allocation details and baseline comparisons are not reported in the registry record.

The record also labels the model single-group. That sits alongside the randomized allocation and two described groups, without an explanation of how the labels fit together. A reader should distinguish the explicit treatment-group descriptions from this unresolved model label.

How should a median time-to-event result be read?

For a time-to-event outcome, each participant contributes information about the time until the event or the end of their observed follow-up. Participants who have not had an event by their last observation are generally treated as censored in standard analyses: their known event-free time contributes information, but their later event time is unknown. This is a general description of survival analysis. The registry record does not report the censoring rules or the handling of missing assessments for this trial.

A median event time is a summary of the estimated distribution of event times. It does not describe the event time of every participant and does not show the full shape of the event-time curve. A 95% confidence interval gives a range of values compatible with the data and the estimation procedure at the stated confidence level. The width of an interval conveys precision: a wider interval indicates greater uncertainty about the estimate than a narrower interval. Neither the median nor its confidence interval is reported for the primary endpoint in this registry record.

The study definition combines radiologically documented progression and death from any cause as PFS events. Local investigator assessment and RECIST v1.1 are specified. Differences in assessment timing, documentation, or unavailable scans can affect when progression is recorded; the record’s endpoint description does not tell how such situations were handled analytically.

What does a hazard ratio represent?

In general, a hazard ratio compares the event rates between groups at a given time among participants who have not yet experienced the event, under the assumptions of the model used. It is not a ratio of medians and is not a direct comparison of the probability that an individual will experience an event. Its interpretation depends on the analysis model and, for a single summary hazard ratio, on whether the relative event rates are sufficiently stable over time. The registry record does not report a hazard ratio, its confidence interval, or a test for the primary PFS comparison. No hazard-ratio interpretation can therefore be made for this trial from the record.

When proportional hazards do not hold, a single hazard ratio may not adequately describe how group differences change over time. General alternatives can include reporting survival probabilities at defined times, comparing restricted mean survival time over a defined horizon, or presenting the survival curves. The registry record does not establish that any of these alternatives was used. They are general methodological options, not trial-specific analyses.

Why do confidence intervals matter?

A point estimate alone gives only one summary value. A confidence interval adds information about statistical uncertainty and helps readers assess which effect sizes are compatible with the observed data under the method’s assumptions. A result can be imprecise even if its point estimate appears notable, and a narrow interval can still include values that matter clinically. The appropriate interpretation depends on the estimate, the interval, the design, and the clinical context. Since the PFS interval is not reported, the precision of the primary comparison cannot be evaluated.

A p-value, if reported, would address how unusual data at least as extreme as those observed would be under a specified null hypothesis and analysis assumptions. It would not measure the probability that the null hypothesis is true, nor the size or importance of an effect. No primary p-value is reported in this registry record. There is consequently no basis for characterizing the primary comparison as statistically significant or not significant.

How should adverse-event counts be interpreted?

Safety counts describe how many participants were reported to have events under the registry’s categories. The serious adverse-event entries report 14 of 47 in the active-dovitinib group and 10 of 50 in the placebo group. The other-adverse-event entries report 47 of 47 and 45 of 50. Such counts are not substitutes for a time-adjusted analysis when exposure or follow-up differs, and participant counts do not necessarily equal the number of event occurrences. The registry record does not report exposure-adjusted rates or a formal between-group safety analysis.

General statistical practice also distinguishes an adverse event from an event judged related to treatment. The listed counts should not be read as treatment-caused events unless the record specifies that relationship. The summary does not provide the adjudication details, severity grading for all events, time at risk, or individual participant narratives. The serious-event terms and their attached percentages offer additional descriptive information, but do not establish comparative risks.

What can the analysis population tell us?

The registered full analysis set consists of all randomized patients. It says participants were analyzed according to the treatment and stratum assigned at randomization, following the intent-to-treat principle. In general, this approach preserves the randomized comparison and estimates the effect of assignment rather than only the effect among participants who completed treatment. The record does not report the number included in each endpoint analysis, exclusions after randomization, or how missing outcome observations were handled.

These principles explain why the missing estimates matter. A valid interpretation requires not only the endpoint label but also the event data, analysis specification, uncertainty estimates, and handling of incomplete observation. Those numerical and procedural details are not reported in the registry record for the primary comparison.

10. Multiplicity, Missing Data and Analysis Populations

The registry lists six outcome measures, including PFS, response, duration of response, overall survival, adverse events, and time to worsening of ECOG performance status. It reports zero analyses. The record does not report a testing hierarchy, a multiplicity adjustment, or which outcomes were considered confirmatory versus exploratory. It is therefore not possible to determine how the trial’s statistical plan addressed the increased chance of false-positive findings when multiple outcomes or comparisons are tested.

In general, multiplicity arises when several hypotheses are evaluated and can make a nominal p-value more likely to appear small by chance. Prespecified priorities and adjustment procedures can control error rates, but the registry record does not describe such procedures for this trial. The presence of several registered outcomes alone does not show that every outcome was tested or that any particular adjustment was used.

The full analysis set is defined as all randomized patients, analyzed according to assigned treatment and stratum, following the intent-to-treat principle. This is an important population definition, but it does not explain how missing endpoint assessments were addressed. The registry record does not report the extent of missing data, censoring rules, imputation, sensitivity analyses, or reasons for missing observations. The primary endpoint’s scheduled assessment interval is stated, but scheduling does not reveal whether each assessment occurred or how missed visits were handled.

Without those details, the potential effect of incomplete follow-up on the PFS estimate cannot be evaluated. The trial’s termination status adds no explanation of missingness or analysis choices; the reason for termination is not reported in the registry record. These gaps limit assessment of the robustness and multiplicity context of any trial conclusion.

11. Safety Results

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

Other (non-serious) adverse events

Participants with at least one non-serious event at or above the registry's 5% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: pulmonary embolism (6.4%), deep vein thrombosis (4.3%), thrombocytopenia (2.1%), pericardial effusion (2.1%), lumbar hernia (2.1%).

The registry reports serious adverse events for 14 of 47 participants receiving fulvestrant with active dovitinib and 10 of 50 receiving fulvestrant with matching placebo. Other adverse events are reported for 47 of 47 and 45 of 50 participants, respectively. These are descriptive participant counts, not a complete comparison of safety over time. The registry record does not report deaths in these group entries.

The listed serious-event terms and attached percentages are pulmonary embolism, 6.4%; deep vein thrombosis, 4.3%; and thrombocytopenia, pericardial effusion, lumbar hernia, and oesophageal varices haemorrhage, 2.1% each. The summary does not specify the denominator or whether percentages refer to participants or events. They should not be converted into event counts or interpreted as rates without that information.

Serious adverse events are not necessarily treatment-related, and the reported counts do not alone establish a difference between groups. Exposure duration, event timing, repeated events, severity details, and treatment attribution are not reported in this summary. The counts describe what the registry records, not a causal safety comparison.

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

The record identifies a randomized, double-blind phase II comparison of fulvestrant with active dovitinib against fulvestrant with matching placebo. It defines PFS as time from randomization to radiologically documented disease progression or death due to any cause, assessed locally using RECIST v1.1. These details make the intended primary question and endpoint understandable.

The record does not report the PFS median in either group, a 95% confidence interval, or a hazard ratio. Thus, it cannot establish from the posted information whether the groups differed in PFS, how large any difference was, or how precisely it was estimated. The absence of a reported estimate is not evidence of no effect; it means the primary numerical result is unavailable in this registry record.

The adverse-event counts and listed serious-event terms describe selected safety information. They do not, without fuller methods and context, show that an event was caused by a treatment or that the groups’ safety profiles differed. No medical conclusion should be drawn from the counts alone.

The record also does not report the reason for termination, a sample-size justification, detailed analysis procedures, missing-data methods, or multiplicity handling. These omissions restrict assessment of design choices and the reliability of any unreported result. The enrollment entry of 97 should be treated as the registry’s recorded enrollment figure, not as a substitute for endpoint-specific analysis counts.

In short, the registry supports a description of the intended comparison, the population, endpoint definitions, and selected adverse-event information. It does not provide enough primary efficacy results to quantify or judge the comparative PFS finding. No conclusion about whether either regimen changes clinical outcomes follows from the information recorded.

13. Why This Trial Matters Statistically

This trial is statistically notable as a randomized comparison with a time-to-event primary endpoint. PFS combines radiologically documented progression and death, and its interpretation depends on both event definitions and follow-up. The scheduled assessments every 8 weeks and the maximum stated timeframe of 34 months describe the intended observation framework, while leaving the actual completeness and duration of participant follow-up unreported.

The contrast is between active dovitinib and matching placebo, each combined with fulvestrant. In general, a randomized placebo-controlled comparison can help separate the effect associated with assignment to the study drug from the shared background regimen. That interpretation still depends on implementation, analysis, and complete reporting. The registry record’s single-group model label conflicts with its randomized two-group descriptions, making transparent handling of registry inconsistencies important.

For biostatistical interpretation, the most consequential limitation is that the primary PFS estimates and their uncertainty are absent. Endpoint definitions alone cannot answer the comparative question. A median, confidence interval, or hazard ratio would be needed to describe the observed time-to-event contrast, and the record contains none. The secondary outcome names and adverse-event counts do not fill that gap.

The case also illustrates why analysis populations, missing-data procedures, multiplicity plans, and the reason for termination matter. These details help readers assess whether the reported comparison matches the randomized question and how robust it is to incomplete information. Their absence does not prove that methods were inadequate; it means those methods cannot be evaluated from this registry record.

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 trial-specific limitations of interpretation follow from the record. The primary PFS outcome is defined, but its group-specific median and 95% confidence interval are not reported. No hazard ratio or primary comparison test is reported either. The clinical question is therefore left without a numerical efficacy estimate in the registry record.

The record is internally inconsistent in describing design: it labels allocation randomized and gives descriptions for active and placebo groups, while also labeling the model single-group. It does not explain this combination. The reason the trial is marked terminated is also not reported, so no conclusion about its operational or scientific context can be drawn from that status.

The registry identifies a full analysis set and an intent-to-treat approach but does not provide endpoint-specific analysis counts, missing-data procedures, or censoring details. It also does not report the planned sample-size justification, multiplicity procedures, or a complete statistical analysis plan. These missing details prevent evaluation of the precision anticipated by the design, the treatment of incomplete follow-up, and the interpretation of multiple outcomes.

Safety reporting is limited in the summary to participant counts and selected serious-event terms with percentages. The denominator for the listed percentages, time at risk, exposure duration, event attribution, and formal comparative analysis are not stated. The record lists six outcome measures and zero analyses, which further limits the available outcome-level context. These are reporting limitations; they do not establish that the underlying trial lacked analyses or procedures.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Trial Evaluating Dovitinib Combined With Fulvestrant, in Postmenopausal Patients With HER2- and HR+ Breast Cancer — NCT01528345.
• Registry record last updated 2016-07-11; status last verified 2016-05.
• Results first posted 2016-07-11.
• 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

The registry describes a phase II, randomized, double-blind, placebo-controlled trial in postmenopausal patients with HER2- and HR+ breast cancer whose disease progressed on or after endocrine therapy. It compares fulvestrant with active dovitinib against fulvestrant with matching placebo. Enrollment is recorded as 97, and status is listed as terminated.

The primary outcome is median PFS based on local investigator assessment using RECIST v1.1, with assessment every 8 weeks up to 34 months. The registry defines PFS as time from randomization to documented progression or death due to any cause. It does not report the median, confidence interval, or hazard ratio.

Serious adverse events are recorded for 14 of 47 participants in the active group and 10 of 50 in the placebo group. The reason for termination, primary efficacy results, detailed missing-data methods, and full analysis plan are not reported in the registry record.