This page provides an independent statistical analysis and educational interpretation of publicly reported results. ClinicalTrials.gov provides the official trial registry record. Numerical trial results on this page are restricted to the results posted in the ClinicalTrials.gov record; calculations added by Clinical Biostats are labelled as such.
1. Trial at a Glance
This page covers the registry results for TRial on the Endocrine Activity of Neoadjuvant Degarelix (NCT02005887), a randomized phase 2 study. The primary outcome is Time to Optimal Ovarian Function Suppression.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT02005887 |
| Phase | Phase 2 |
| Condition | Breast Cancer Invasive Nos |
| Allocation | Randomized |
| Design model | Parallel |
| Masking | None (open label) |
| Enrollment | 51 |
| Arms in the primary outcome | 2 |
| Lead sponsor | ETOP IBCSG Partners Foundation |
| Results posted | Yes |
2. Clinical Question
The trial compared two ways of suppressing ovarian function during neoadjuvant letrozole treatment for premenopausal patients with primary endocrine responsive breast cancer. The primary question was how long it took after the first injection of degarelix or triptorelin for a centrally assessed estradiol level to reach the study’s range for optimal ovarian function suppression. The study also recorded several secondary outcomes related to disease response and surgery.
Population
Premenopausal patients receiving letrozole for primary endocrine responsive breast cancer. The registry record identifies the condition as invasive breast cancer, NOS. Further eligibility details are not reported in the registry record.
Intervention
Degarelix plus letrozole. Degarelix was given by subcutaneous injection on day 1 of cycle 1, followed by injections on day 1 of cycles 2 to 6. Letrozole was taken daily for 6 cycles.
Comparator
Triptorelin plus letrozole. Triptorelin was given by intramuscular injection on day 1 every 28 days for 6 cycles, with daily letrozole for 6 cycles.
Primary question
What is the median time from the first injection to the first centrally assessed estradiol level in the optimal suppression range during the 6 cycles of neoadjuvant treatment, and how do the arm-specific results compare descriptively?
The registry record gives arm-specific medians and 95% confidence intervals for this endpoint. It does not report a formal sponsor analysis comparing the arms, so the posted medians describe the observed results without establishing a comparative treatment effect.
3. Trial Design
This was a randomized, open-label, parallel-group phase II trial. The registry lists an enrollment of 51 and a completed status. The study start is recorded as 2014-02, and primary completion as 2017-08-25. The sponsor was ETOP IBCSG Partners Foundation.
Participants were assigned to one of two treatment regimens: triptorelin plus letrozole, or degarelix plus letrozole. Both regimens included letrozole for 6 cycles. Triptorelin was administered intramuscularly at 3.75 mg on day 1 every 28 days for 6 cycles. Degarelix was administered subcutaneously at 240 mg on day 1 of cycle 1, followed by 80 mg on day 1 of cycles 2 to 6. The registry describes no masking.
The registry reports 26 participants in the triptorelin arm and 25 in the degarelix arm for the primary endpoint. These arm-specific counts describe the endpoint records; the record does not explain how they relate to enrollment or whether all randomized participants contributed to every outcome.
The stated primary endpoint was time to optimal ovarian function suppression, measured during the treatment period of up to 24 weeks. Secondary outcomes listed in the registry include Ki67 proliferation marker changes, PEPI score, best overall disease response, node-negative disease at surgery, breast-conserving surgery, and patient-reported symptoms. Numerical registry results are present for three of these secondary outcomes. Results for Ki67, PEPI, and patient-reported symptoms are not reported in the registry record.
Details of the randomization procedure, allocation concealment, protocol deviations, and analysis populations are not reported in the registry record. The registry also does not report the trial’s sample-size justification or a 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
| Stage | Arm A: Triptorelin + Letrozol | Arm B: Degarelix + Letrozol |
|---|---|---|
| STARTED | 26 | 25 |
| COMPLETED | 26 | 23 |
| NOT COMPLETED | 0 | 2 |
Reasons for not completing this period:
| Reason | Arm A: Triptorelin + Letrozol | Arm B: Degarelix + Letrozol |
|---|---|---|
| Protocol Violation | 0 | 2 |
5. Baseline Characteristics
The table reproduces the baseline characteristics posted in the registry, which describe the participants analysed at baseline and help show whether the randomized groups were comparable.
| Characteristic | Unit | Arm A: Triptorelin + Letrozol | Arm B: Degarelix + Letrozol | Total |
|---|---|---|---|---|
| Participants analysed | 26 | 25 | 51 | |
| Age, Continuous | years | 44.0 (42.2 to 47.5) | 45.0 (42.0 to 50.0) | 44.0 (42.0 to 48.5) |
| Sex: Female, Male: Female | Participants | 26 | 25 | 51 |
| Sex: Female, Male: Male | Participants | 0 | 0 | 0 |
| Race and Ethnicity Not Collected | Participants | — | — | 0 |
| Region of Enrollment: Italy | Participants | 26 | 25 | 51 |
6. Primary Endpoint
The registry lists the primary outcome as Time to Optimal Ovarian Function Suppression, measured over up to 24 weeks.
| Element | Registry entry |
|---|---|
| Result type | Median |
| Measure of spread | 95% Confidence Interval |
| Unit | days |
| Endpoint classification | Time-to-Event Analysis |
The primary endpoint measures the time from the first injection of degarelix or triptorelin to the first assessment of centrally assessed 17-β-estradiol (E2) in the study-defined range for optimal ovarian function suppression: ≤2.72 pg/mL or ≤10 pmol/L. The assessment was made during the 6 cycles of neoadjuvant treatment, with the endpoint timeframe stated as up to 24 weeks. The reported summary is the median time in days, with a 95% confidence interval for each arm.
As a general statistical concept, a time-to-event endpoint records how long it takes for a defined event to occur. In this trial, the event was the first qualifying estradiol assessment, not a clinical event such as disease progression. The median provides a group-level description of the time distribution: it identifies the point by which half of the observed times are at or below the estimate, subject to the analysis and data handling used.
The endpoint uses a laboratory measure as an indicator of ovarian function suppression. That makes it relevant to the trial’s endocrine focus, but it is not itself a measure of tumor response, surgery, symptoms, or long-term outcomes. The registry does not report the frequency or timing of assessments, how observations without a qualifying result were handled, or the specific statistical procedure used to estimate the medians and confidence intervals. Those details matter when interpreting time-to-event results, especially if some participants do not experience the defined event within the observation period.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The median time to the first qualifying estradiol assessment was 14.0 days in the triptorelin-plus-letrozole arm, with a 95% confidence interval from 8.0 to 14.0 days. In the degarelix-plus-letrozole arm, the median was 3.0 days, with a 95% confidence interval from 3.0 to 3.0 days. Descriptively, the posted median was earlier in the degarelix arm. These are arm-specific summaries, not a reported estimate of the between-arm effect.
The registry record does not report a sponsor analysis comparing the primary endpoint between arms, such as a hazard ratio or a test of the difference. A formal comparative result and its uncertainty therefore cannot be read from these medians alone. The confidence intervals describe uncertainty around each arm’s median under the method used, but they do not substitute for a confidence interval for a direct treatment comparison. The degarelix interval has identical displayed bounds; the registry does not explain the estimation details behind that result.
For the secondary outcomes with numerical results, the arm-specific estimates show a mixed descriptive pattern: best overall disease response was close between arms, while the degarelix arm had higher point estimates for node-negative disease at surgery and breast-conserving surgery. The posted risk-difference confidence intervals for all three outcomes include zero. The unadjusted recalculated p-values are 0.877, 0.525, and 0.49, respectively. These results do not establish that the arms differ, nor do they establish that they are equivalent. The estimates are imprecise, and the registry does not report sponsor analyses for these outcomes.
The registry reports no serious adverse events and no deaths in either arm. It reports other adverse events affecting 23 participants in each arm. These counts should be read as a description of what was recorded, not as a complete characterization of event types, severity, duration, or comparative safety. Serious adverse event terms are not listed.
Overall, the primary endpoint summaries describe earlier observed median time to the laboratory threshold in the degarelix arm, while the record does not provide a formal comparative analysis. The secondary outcomes offer additional descriptive information but are not a substitute for that missing primary comparison. The study’s enrollment and the limits of the registry reporting warrant restraint in drawing broader conclusions.
9. Statistical Methods Explained
The primary result is reported as a median time in days with a 95% confidence interval. The secondary binary outcomes are reported as percentages with 90% confidence intervals. Some posted comparisons have also been recalculated from the displayed summary statistics; those are unadjusted comparisons rather than sponsor-reported analyses. The registry lists no reported analyses.
What does the median describe?
As a general statistical explanation, the median is a measure of the center of a distribution. For a time-to-event outcome, it refers to the time by which half of the relevant event-time distribution has reached the event, as estimated using the analysis method. It is not the average time, and it does not describe every participant’s experience. The registry reports arm medians, but does not report enough analysis detail to determine how observations without a qualifying estradiol result were handled or which estimator was used.
How should the confidence intervals be read?
A confidence interval gives a range of values compatible with the data under a specified statistical procedure and its assumptions. In general, a wider interval indicates less precision, while a narrower interval indicates more precision under that procedure. The primary endpoint intervals apply to each arm’s median, not to the difference between arms. The degarelix median and its interval are all reported as 3.0 days; the registry record does not provide further detail about how that interval was derived. The 90% intervals for the secondary percentages and the 95% intervals for the primary medians have different stated confidence levels and should not be treated as directly interchangeable.
Why is a direct comparison different from comparing arm summaries?
A direct comparison estimates how much the outcome differs between treatment groups and quantifies uncertainty around that contrast. Looking at two separate arm estimates is not the same calculation. For binary outcomes, the recalculated risk difference is a comparison of the proportions in the two arms. A confidence interval for that difference that includes zero means the data are compatible with no difference as well as with differences in either direction. It does not prove that the groups are identical. The registry does not report sponsor analyses for the posted secondary outcomes, and no direct primary comparison is reported.
The listed secondary p-values are unadjusted recalculations. A p-value measures how unusual data at least as extreme as those observed would be under a specified null model and assumptions; it is not the probability that the null hypothesis is true, and it does not measure clinical importance. Without adjustment for the number of outcomes examined, unadjusted secondary results carry less weight than a prespecified, appropriately analyzed primary comparison. The registry record does not report a multiplicity plan.
What do the planning illustrations mean?
The planning illustrations use the observed effect, with scenarios for planning for 100%, 75%, or 50% of that observed effect. Their stated assumptions are a two-sided significance level of 0.05, equal allocation between arms, and a normal approximation. The binary-outcome illustrations express the result as participants per arm for 80% or 90% power. They are hypothetical planning calculations based on observed effects, not the trial’s original design justification and not observed power. The registry does not report the sample-size justification used to plan this trial.
Over-dispersion is a general concern when outcome variability is greater than a statistical model assumes; if not accommodated, standard errors and uncertainty estimates may be too small. The registry’s primary result is a median time endpoint, and the available record does not identify a model or report information that would support evaluating over-dispersion. The binary secondary summaries also do not include sufficient detail to assess model-based dispersion assumptions.
For time-to-event analyses, censoring can matter when an event has not been observed by the end of follow-up or when observation ends earlier. The registry reports a timeframe of up to 24 weeks but does not describe censoring, incomplete follow-up, missing measurements, or how such records contributed to the median. It also does not report a hazard ratio. As a general method, hazard ratios compare event rates over time under model assumptions, but no such result can be interpreted from the arm-specific medians alone.
10. Multiplicity, Missing Data and Analysis Populations
The registry lists several secondary outcomes in addition to the primary endocrine endpoint. When many outcomes are examined, unadjusted statistical results can be difficult to interpret because the chance of at least one apparently unusual result may rise. As a general principle, a multiplicity plan clarifies which comparisons are confirmatory and whether the significance threshold or inference is adjusted across outcomes. Such a plan is not reported in the registry record. The secondary p-values available are unadjusted recalculations, not sponsor-reported analyses.
The registry does not report a statistical analysis plan, whether the primary endpoint was analyzed according to intention to treat or another population, or how protocol deviations were handled. It also does not report a missing-data strategy, reasons for missing observations, or sensitivity analyses. These omissions make it difficult to assess whether the analyzed participants and measurements correspond to the intended trial population and follow-up.
The primary endpoint counts are reported as 26 in the triptorelin arm and 25 in the degarelix arm. The registry does not explain whether these are all randomized participants or how any unavailable endpoint observations were treated. For the surgery outcomes, the reported arm counts are 26 and 23. The reason for the difference in those denominators is not reported in the registry record. No assumption should be made about why an outcome count differs from another.
Although six secondary outcomes are listed, numerical result details are reported for best overall response, node-negative disease at surgery, and breast-conserving surgery. Numerical results for Ki67, PEPI, and patient-reported symptoms are not reported in the registry record. The registry also gives no detailed account of assessment schedules, adjudication beyond the central estradiol assessment, or follow-up completeness. These reporting gaps constrain assessment of multiplicity, missingness, and the robustness of the reported findings.
11. Safety Results
The registry reports serious adverse events as affected participants divided by participants at risk.
| Arm | Participants with serious adverse events | Participants at risk | Percentage |
|---|---|---|---|
| Arm A: Triptorelin + Letrozol | 0 | 26 | 0.0% |
| Arm B: Degarelix + Letrozol | 0 | 25 | 0.0% |
Deaths
| Arm | Deaths (participants affected of at risk) |
|---|---|
| Arm A: Triptorelin + Letrozol | 0 of 26 |
| Arm B: Degarelix + Letrozol | 0 of 25 |
Other (non-serious) adverse events
Participants with at least one non-serious event at or above the registry's 0% reporting threshold.
| Arm | Participants affected of at risk |
|---|---|
| Arm A: Triptorelin + Letrozol | 23 of 26 |
| Arm B: Degarelix + Letrozol | 23 of 25 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Arm A: Triptorelin + Letrozol | Arm B: Degarelix + Letrozol |
|---|---|---|---|
| Hot Flashes/Flushes | Vascular disorders | 18 of 26 | 20 of 25 |
| Arthralgia | Musculoskeletal and connective tissue disorders | 14 of 26 | 8 of 25 |
| Insomnia | Psychiatric disorders | 3 of 26 | 6 of 25 |
| Injection Site Reaction | General disorders and administration site conditions | 0 of 26 | 6 of 25 |
| Nausea | Gastrointestinal disorders | 1 of 26 | 4 of 25 |
| Fatigue | General disorders and administration site conditions | 3 of 26 | 1 of 25 |
| Anxiety | Psychiatric disorders | 2 of 26 | 2 of 25 |
| Hypertension | Vascular disorders | 1 of 26 | 3 of 25 |
| Myalgia | Musculoskeletal and connective tissue disorders | 2 of 26 | 1 of 25 |
| Depression | Psychiatric disorders | 1 of 26 | 2 of 25 |
The registry reports 0 serious adverse events among 26 participants at risk in the triptorelin-plus-letrozole arm, and 0 among 25 participants at risk in the degarelix-plus-letrozole arm. It also reports 0 deaths in each arm. Other adverse events are recorded for 23 participants in each arm, with 26 and 25 participants at risk, respectively.
These figures are counts recorded for the trial arms. They do not provide a description of the types of other adverse events, their severity, duration, timing, or relationship to treatment. Serious adverse event terms are not listed in the registry record. The record also does not state how adverse events were collected, coded, or assessed for causality. The figures therefore describe the posted safety counts but do not support a detailed comparison of event profiles. Zero recorded serious adverse events should not be interpreted as proof that serious events cannot occur or that the regimens have identical safety.
12. What the Result Does, and Does Not, Mean
The primary endpoint results describe the time to the first centrally assessed estradiol level in the study-defined suppression range. The reported median was 14.0 days with triptorelin plus letrozole and 3.0 days with degarelix plus letrozole. These are arm-specific summaries from a randomized phase II trial. The registry does not report a formal sponsor comparison, so the medians alone do not establish the size or statistical certainty of a between-arm difference.
The result is specific to a laboratory threshold observed during neoadjuvant treatment. It does not directly answer whether one regimen leads to better disease control, different surgical outcomes, improved symptoms, or longer-term benefit. The available secondary results are limited and imprecise, and results for several listed outcomes are not reported in the registry record. No advice about treatment choice follows from these registry summaries.
As a general statistical point, lack of a reported statistically significant comparison would not establish equivalence, and a numerical difference in arm estimates would not by itself establish a treatment effect. Evidence about a comparative effect requires an appropriate direct analysis, with its uncertainty and assumptions made clear. The registry record does not provide that analysis for the primary endpoint.
The trial is also limited by its reported enrollment and by missing information about the analysis population, missing data, multiplicity, and endpoint estimation. These limitations affect how precisely and confidently the posted summaries can be interpreted. The data can describe what the registry records for each arm; they cannot, on their own, establish a comprehensive comparative benefit-risk profile or resolve questions not measured or reported.
13. Why This Trial Matters Statistically
This trial is statistically informative because it distinguishes a biologic time-to-threshold endpoint from clinical and surgical outcomes. Time to an estradiol measurement in a specified range is not the same estimand as disease response or surgery. Keeping those questions separate helps avoid treating a laboratory endpoint as if it directly answered every question about treatment effects.
Randomized allocation is an important design feature for comparing groups, while the open-label design and limited registry analysis details remain relevant when interpreting results. The registry provides arm-specific medians and confidence intervals for the primary endpoint, but not a sponsor-reported direct comparison. That distinction is a useful example of why descriptive estimates and comparative inference should not be conflated.
The record also illustrates how uncertainty and reporting completeness matter in a phase II trial. The confidence intervals communicate uncertainty around the arm-specific estimates, while the absence of a reported primary comparison, analysis plan, and missing-data approach limits what can be inferred. Secondary outcomes can broaden the clinical context, but unadjusted results across several outcomes should be interpreted cautiously, particularly when some listed outcomes lack numerical results.
Finally, the planning illustrations are not evidence of the trial’s observed power or original design rationale. They are hypothetical calculations based on observed effects and stated assumptions. Separating such planning exercises from trial results is essential: a small observed study can generate estimates for future planning, but those estimates remain uncertain and do not replace a prespecified sample-size justification or a clearly reported analysis.
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 record does not report the sample-size justification, statistical analysis plan, randomization procedure, allocation concealment, or analysis population. It does not describe missing-data handling, reasons for missing measurements, protocol deviations, or sensitivity analyses. Those omissions limit evaluation of how the primary and secondary results were generated and how robust they may be.
The primary result is presented as arm-specific medians and confidence intervals without a reported sponsor comparison. The record does not explain the estimator, censoring approach, assessment schedule, or handling of participants without a qualifying estradiol result. The degarelix median and confidence interval are all reported as 3.0 days; the registry does not provide further detail about the apparent precision of that estimate.
Numerical secondary results are available for three outcomes, while the registry lists six secondary outcomes. Results for Ki67, PEPI, and patient-reported symptoms are not reported in the registry record. The available secondary comparisons are unadjusted recalculations, and no multiplicity approach is reported. The registry’s surgical outcome counts differ between arms, but the reason is not reported in the registry record.
The trial was open-label, and the record does not describe blinding of outcome assessment beyond stating that the estradiol assessment was central. Adverse-event reporting is also limited: counts are given, but serious event terms are not listed and details about other adverse events are not reported. These trial-specific reporting limitations, together with the modest enrollment, counsel against treating the posted summaries as a complete or definitive account of comparative effects.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: TRial on the Endocrine Activity of Neoadjuvant Degarelix — NCT02005887.
- Registry record last updated 2026-09-02; status last verified 2019-05.
- Results first posted 2019-05-29.
- Data retrieved from ClinicalTrials.gov on 2026-11-09.
- Group sizes, means, event counts and sponsor-reported p-values are reproduced as posted. Effect estimates, confidence intervals and p-values not attributed to the sponsor are independently calculated from the posted summary statistics.
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18. Record Summary
NCT02005887 is a completed randomized, open-label, parallel-group phase II trial sponsored by ETOP IBCSG Partners Foundation. It enrolled 51 participants and compared neoadjuvant letrozole with either triptorelin or degarelix in premenopausal patients with primary endocrine responsive breast cancer.
The primary endpoint was time to optimal ovarian function suppression, defined by the first centrally assessed estradiol result in the stated range during treatment. The registry reports arm-specific medians and 95% confidence intervals but no sponsor-reported comparative analysis. Numerical results are also reported for three secondary outcomes; results for the remaining listed secondary outcomes are not reported in the registry record. The registry reports no serious adverse events and no deaths in either arm, but provides limited detail on event types and analysis methods.