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 A Study to Assess the Safety and Efficacy of the VEGFR-FGFR-PDGFR Inhibitor, Lucitanib, Given to Patients With Metastatic Breast Cancer (NCT02202746), a non-randomized phase 2 study. The primary outcome is Progression Free Survival (PFS) According to RECIST Version 1.1 as Determined by the Investigator.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT02202746 |
| Phase | Phase 2 |
| Condition | Breast Cancer, Metastatic Breast Cancer, MBC |
| Allocation | Non-Randomized |
| Design model | Parallel |
| Masking | None (open label) |
| Enrollment | 178 |
| Arms in the primary outcome | n/a |
| Lead sponsor | Clovis Oncology, Inc. |
| Results posted | Yes |
2. Clinical Question
Population
Patients with metastatic breast cancer and FGF-related biomarker classifications. The study description includes patients with FGFR1 amplification, 11q amplification, or neither. The efficacy population was defined as patients who received at least one dose of lucitanib and had a qualifying biomarker classification confirmed by the central laboratory.
Intervention
Oral lucitanib, given once daily. The registry describes a 10 mg cohort for patients with FGFR1 amplification or 11q amplification, a 15 mg cohort for patients with both amplifications, and a 10 mg cohort for patients with neither amplification.
Comparator
There was no randomized control group. The study was non-randomized and open-label. Its dose and biomarker cohorts are not like-for-like control groups, so differences between them cannot be interpreted as randomized treatment effects.
Primary question
The primary efficacy question was how long patients remained alive without investigator-determined disease progression while receiving study treatment, according to RECIST v1.1. The registry identifies progression-free survival as the primary endpoint but does not report its median, confidence interval, or a sponsor-reported hazard ratio.
The study was designed to examine lucitanib in FGF-aberrant metastatic breast cancer and in biomarker-negative, or FGF non-aberrant, metastatic breast cancer. The registry also lists response rate, duration of response, disease control, and pharmacokinetic comparisons among secondary outcomes. Those objectives do not turn the cohorts into randomized comparisons: biomarker status and dose define the groups, and the record does not describe random assignment to them.
3. Trial Design
This was a phase 2, open-label, multicenter study of oral lucitanib. Allocation is recorded as non-randomized, with a parallel model and no masking. The registry lists enrollment of 178 and describes three biomarker-defined cohorts: 10 mg daily for FGFR1-amplified or 11q-amplified disease; 15 mg daily for disease with both amplifications; and 10 mg daily for disease with neither amplification. The adverse-event groups are reported by dose, with 109 participants in the 10 mg group and 69 in the 15 mg group.
The study began on 2014-09-09, had primary completion on 2017-01-17, and is recorded as terminated. The registry record does not state the reason for termination. It also does not provide an account of how participants were assigned to the biomarker or dose cohorts, whether dose decisions followed a prespecified rule, or whether any changes were made to the planned design.
The primary endpoint was investigator-determined progression-free survival by RECIST v1.1. Secondary outcomes included objective response rate, duration of response, and disease control rate, also by RECIST v1.1. The registry additionally lists pharmacokinetic and relative bioavailability comparisons between capsule and tablet formulations. The record does not report results for those outcomes in the information available for this analysis. Because treatment was open-label and assignment was not randomized, the design is descriptive and exploratory rather than a controlled test of comparative treatment effects.
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 | Lucitanib (CO-3810) 10 mg QD | Lucitanib (CO-3810) 15 mg QD |
|---|---|---|
| STARTED | 109 | 69 |
| COMPLETED | 109 | 69 |
| NOT COMPLETED | 0 | 0 |
Analysis population for the primary outcome, as defined in the registry: Efficacy population: all patients who have received at least one dose of lucitanib and are confirmed as FGR1-, 11q-amplified, or FGF non-amplified per the central laboratory
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 | Lucitanib (CO-3810) 10 mg QD | Lucitanib (CO-3810) 15 mg QD | Total |
|---|---|---|---|---|
| Participants analysed | 109 | 69 | 178 | |
| Age, Continuous | years | 57.0 (27 to 82) | 53.0 (27 to 80) | 55.0 (27 to 82) |
| Sex: Female, Male: Female | Participants | 109 | 67 | 176 |
| Sex: Female, Male: Male | Participants | 0 | 2 | 2 |
| Race/Ethnicity, Customized: White | Participants | 87 | 61 | 148 |
| Race/Ethnicity, Customized: Asian | Participants | 5 | 3 | 8 |
| Race/Ethnicity, Customized: Black | Participants | 10 | 1 | 11 |
| Race/Ethnicity, Customized: Not provided | Participants | 4 | 3 | 7 |
| Race/Ethnicity, Customized: Unknown/Not assessed | Participants | 2 | 1 | 3 |
| Race/Ethnicity, Customized: Other | Participants | 1 | 0 | 1 |
| Race/Ethnicity, Customized: Hispanic or Latino | Participants | 8 | 6 | 14 |
| Race/Ethnicity, Customized: Not Hispanic or Latino | Participants | 97 | 61 | 158 |
| Race/Ethnicity, Customized: Not Provided | Participants | 4 | 2 | 6 |
| Number of Prior Anticancer Therapies | Therapies | 6.0 (1 to 18) | 6.0 (1 to 16) | 6.0 (1 to 18) |
| Fibroblast Growth Factor (FGF) Status: 11q | Participants | 34 | 25 | 59 |
| Fibroblast Growth Factor (FGF) Status: FGFR1 | Participants | 50 | 28 | 78 |
| Fibroblast Growth Factor (FGF) Status: FGFR1 & 11q | Participants | 18 | 10 | 28 |
| Fibroblast Growth Factor (FGF) Status: Negative | Participants | 7 | 6 | 13 |
6. Primary Endpoint
The registry lists the primary outcome as Progression Free Survival (PFS) According to RECIST Version 1.1 as Determined by the Investigator, measured over From Cycle 1 Day 1 until disease progression or end of treatment, whichever came first, assessed up to 29 months.
| Element | Registry entry |
|---|---|
| Result type | Median |
| Measure of spread | 95% Confidence Interval |
| Unit | Days |
| Endpoint classification | Time-to-Event Analysis |
Progression-free survival measures the time from treatment initiation until disease progression or death, whichever occurs first. For this study, the registry says the endpoint was calculated as 1+ the number of days from the first dose to progression or death from any cause. Progression was determined by the investigator using RECIST v1.1. The definition includes a specified increase in the sum of target-lesion diameters, with an absolute increase requirement, or the appearance of new lesions.
Patients without a documented progression event were censored at their last adequate tumor assessment, or at randomization if no tumor assessment was performed. Censoring means that the exact event time is not observed for that patient; their available follow-up contributes information up to the censoring time. The registry's censoring description refers to randomization even though allocation is recorded as non-randomized, a wording ambiguity that should be kept in mind.
In general, progression-free survival is used to describe the duration before progression or death and can incorporate follow-up from patients whose event has not yet occurred. The registry lists the endpoint as a median with a 95% confidence interval, but it does not report the median or interval. Consequently, the posted record does not establish the observed duration of progression-free survival or the precision of its estimate.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The registry record identifies progression-free survival as the primary efficacy endpoint and describes how it was defined and assessed. It does not report the primary endpoint result: no median progression-free survival or 95% confidence interval is listed. Although the analysis description says progression-free survival is a time-to-event measure and the record indicates that only sponsor-reported hazard ratios are used for this measure, no hazard ratio is reported. There is therefore no numerical efficacy estimate in this record on which to base a conclusion about the observed time to progression or death.
The study enrolled 178 participants and is marked terminated. Neither the termination reason nor a narrative explanation of the study's conduct is reported in the registry record. Enrollment is a design and conduct detail, not an outcome. It cannot fill the gap left by the absent endpoint estimate.
The reported groups reflect dose and biomarker categories in a non-randomized, open-label study. They should not be treated as randomized treatment and control groups. Differences among groups, if considered, could reflect biomarker status, dose selection, participant characteristics, or other differences in care and follow-up. The registry does not provide a basis for isolating a causal dose effect or a causal effect of lucitanib relative to another treatment.
Safety information is reported by two dose groups. The 10 mg group lists 109 participants at risk for serious adverse events, with 31 affected, and 5 deaths. The 15 mg group lists 69 at risk, with 22 affected, and 7 deaths. These descriptive counts do not establish that one dose is safer than another. The record also lists serious adverse-event terms and percentages, but does not provide enough context in those entries to interpret each percentage as a comparative risk estimate.
In general, statistical precision is conveyed by the uncertainty around an estimate, such as a confidence interval. Since the primary median and its interval are not reported, precision cannot be assessed. The record's listed secondary endpoints also do not substitute for the missing primary result: their numerical results are not reported in the registry record analyzed. No effectiveness or comparative-effectiveness conclusion follows from the available registry entries.
9. Statistical Methods Explained
What does a median time-to-event result describe?
In general, a median time-to-event result is the time by which half of the analyzed population has experienced the event, as estimated from the observed event and censoring information. For progression-free survival, the event is progression or death, whichever occurs first. This type of summary uses follow-up duration, rather than only counting whether an event happened at a single assessment. It is useful when participants have different follow-up times or when some remain event-free at the end of observation.
The registry specifies a median and a 95% confidence interval as the primary endpoint summary. A confidence interval describes statistical uncertainty around an estimated quantity under the assumptions of the analysis. A narrower interval generally indicates greater precision, while a wider interval indicates greater uncertainty. The median and interval are not reported in the registry record, so neither the estimated duration nor its statistical precision can be assessed.
How should progression-free survival be read?
The endpoint begins at the first dose of study drug and ends at disease progression or death from any cause. Progression is investigator-determined under RECIST v1.1, which uses changes in target lesions and the appearance of new lesions. The registry states that the progression definition requires both a relative increase in the sum of target-lesion diameters and a minimum absolute increase, or a new lesion. The record describes censoring at the last adequate tumor assessment for patients without a documented progression event, with an alternative censoring date if no tumor assessment was performed.
In general, censoring is not the same as an event. It indicates that the event time is unknown beyond the last point at which the participant was assessed. Time-to-event methods rely on assumptions about how censoring relates to the chance of the event. The record does not provide enough analysis detail to assess those assumptions. Its reference to censoring at randomization is also difficult to reconcile with the non-randomized allocation listed for the study.
Why does non-randomized allocation matter?
In general, randomization helps balance measured and unmeasured participant characteristics across assigned groups, supporting a fair treatment comparison. This study is recorded as non-randomized. Its cohorts are organized by biomarker status and dose, so those groups may differ in prognosis or other characteristics before treatment. The registry record does not describe an adjusted comparison that would address those differences. Consequently, a contrast between cohorts would not by itself identify a causal effect of dose or biomarker status.
Open-label conduct means the study is recorded as having no masking. In general, awareness of treatment can influence clinical assessment and decisions. Since progression was determined by the investigator, an unmasked assessment may be relevant when interpreting the endpoint. The registry does not report whether any independent review of progression was conducted.
What do hazard ratios and planning illustrations add?
In general, a hazard ratio summarizes the relative event rate over follow-up for a comparison between groups, subject to the model and assumptions used. The registry record indicates that sponsor-reported hazard ratios are the basis for time-to-event interpretation, but no hazard ratio or comparison result is reported. A hazard ratio cannot be inferred from a median alone, and no such inference is made.
The sample-size assumptions describe planning illustrations based on an observed effect, using a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. For time-to-event illustrations, the quantity is a total number of events; other illustrations are expressed as participants per arm. The assumed effect is a stated fraction of the observed effect. These are planning illustrations, not observed power and not evidence that the trial was designed or sized in this way. The actual illustration values are not reported in the registry record. The record also does not report a protocol-based sample-size justification, so the illustration assumptions should not be mistaken for the study's original design rationale.
10. Multiplicity, Missing Data and Analysis Populations
The registry lists multiple outcomes: progression-free survival as the primary endpoint, along with objective response rate, duration of response, disease control rate, and pharmacokinetic and bioavailability measures. When several outcomes or comparisons are examined, the chance of at least one apparently notable result can increase. In general, multiplicity procedures can control or otherwise address this issue, but the registry record does not report a multiplicity adjustment, a hierarchy of secondary tests, or a prespecified testing strategy. It also does not report numerical results for the listed secondary outcomes in the record analyzed.
Missing-data methods are not described in sufficient detail to assess how missing assessments or incomplete follow-up were handled beyond the stated censoring rule for progression-free survival. The endpoint description specifies censoring at the last adequate tumor assessment for patients without a documented event, or at randomization if no tumor assessment was performed. It does not report the frequency or reasons for missing tumor assessments, the number censored, or sensitivity analyses. The reference to randomization is notable because the study is listed as non-randomized.
The efficacy population is described as patients who received at least one dose and had the relevant biomarker classification confirmed by the central laboratory. The record does not provide the population's analyzed size or explain whether every endpoint used the same analysis population. The registry's broader enrollment count should not be assumed to equal the number analyzed for the primary endpoint. Details of the statistical analysis plan, interim analyses, and handling of deviations from the intended analyses are not reported in the registry record.
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 |
|---|---|---|---|
| Lucitanib (CO-3810) 10 mg QD | 31 | 109 | 28.4% |
| Lucitanib (CO-3810) 15 mg QD | 22 | 69 | 31.9% |
Deaths
| Arm | Deaths (participants affected of at risk) |
|---|---|
| Lucitanib (CO-3810) 10 mg QD | 5 of 109 |
| Lucitanib (CO-3810) 15 mg QD | 7 of 69 |
Other (non-serious) adverse events
Participants with at least one non-serious event at or above the registry's 5% reporting threshold.
| Arm | Participants affected of at risk |
|---|---|
| Lucitanib (CO-3810) 10 mg QD | 107 of 109 |
| Lucitanib (CO-3810) 15 mg QD | 69 of 69 |
Most frequent serious adverse event terms
| Event term | Organ system | Lucitanib (CO-3810) 10 mg QD | Lucitanib (CO-3810) 15 mg QD |
|---|---|---|---|
| Malignant neoplasm progression | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | 5 of 109 | 5 of 69 |
| Hyponatraemia | Metabolism and nutrition disorders | 3 of 109 | 1 of 69 |
| Hypoxia | Respiratory, thoracic and mediastinal disorders | 1 of 109 | 3 of 69 |
| Hypertension | Vascular disorders | 2 of 109 | 2 of 69 |
| Nausea | Gastrointestinal disorders | 1 of 109 | 2 of 69 |
| Pneumonia | Infections and infestations | 2 of 109 | 1 of 69 |
| Dyspnoea | Respiratory, thoracic and mediastinal disorders | 2 of 109 | 1 of 69 |
| Pleural effusion | Respiratory, thoracic and mediastinal disorders | 2 of 109 | 1 of 69 |
| Dysphagia | Gastrointestinal disorders | 2 of 109 | 0 of 69 |
| Gastrointestinal haemorrhage | Gastrointestinal disorders | 1 of 109 | 1 of 69 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Lucitanib (CO-3810) 10 mg QD | Lucitanib (CO-3810) 15 mg QD |
|---|---|---|---|
| Hypertension | Vascular disorders | 85 of 109 | 50 of 69 |
| Fatigue | General disorders | 55 of 109 | 37 of 69 |
| Nausea | Gastrointestinal disorders | 53 of 109 | 33 of 69 |
| Hypothyroidism | Endocrine disorders | 41 of 109 | 34 of 69 |
| Headache | Nervous system disorders | 42 of 109 | 24 of 69 |
| Vomiting | Gastrointestinal disorders | 35 of 109 | 24 of 69 |
| Decreased appetite | Metabolism and nutrition disorders | 36 of 109 | 21 of 69 |
| Diarrhoea | Gastrointestinal disorders | 33 of 109 | 19 of 69 |
| Proteinuria | Renal and urinary disorders | 22 of 109 | 22 of 69 |
| Dyspnoea | Respiratory, thoracic and mediastinal disorders | 22 of 109 | 14 of 69 |
Serious events with the highest arm-level rate: malignant neoplasm progression (7.2%), hypoxia (4.3%), nausea (2.9%), vomiting (2.9%), hypertension (2.9%).
The registry reports serious adverse-event information for two lucitanib dose groups. For the 10 mg group, 109 participants were at risk, 31 were reported as affected by serious adverse events, and 5 deaths were listed. For the 15 mg group, 69 participants were at risk, 22 were reported as affected, and 7 deaths were listed. These are group-level counts; they do not by themselves show whether an event was caused by treatment, nor do they account for differences in follow-up or participant characteristics.
The registry lists malignant neoplasm progression at 7.2%, hypoxia at 4.3%, nausea at 2.9%, vomiting at 2.9%, hypertension at 2.9%, and hyponatraemia at 2.8% among the top serious adverse-event terms. These entries are descriptive listings, not adjusted comparisons between dose groups. The record does not specify a comparative analysis for these terms. In general, serious adverse-event counts and event-term percentages answer different descriptive questions and should not be read as a direct measure of treatment benefit or comparative safety.
12. What the Result Does, and Does Not, Mean
The registry record documents a phase 2 study of lucitanib in metastatic breast cancer with biomarker-defined cohorts and identifies investigator-assessed progression-free survival as the primary endpoint. It also provides study status, enrollment, cohort descriptions, and some serious adverse-event counts. This information describes the study's scope and selected reported safety observations.
The record does not report the primary progression-free survival median, its 95% confidence interval, or a sponsor-reported hazard ratio. It therefore cannot show the estimated duration of progression-free survival, the precision of that estimate, or a comparative time-to-event effect. Numerical results for the listed secondary outcomes are also not reported in the record analyzed. The absence of those results is not evidence that an outcome was favorable, unfavorable, or unchanged.
In general, an uncontrolled or non-randomized study can provide descriptive evidence about outcomes among treated participants, but cohort differences cannot be attributed to treatment with the same confidence as a randomized comparison. Here, dose groups are not randomized controls, and the study is open-label. The record does not report an analysis that addresses potential baseline differences between groups. The available serious adverse-event counts should therefore be treated as descriptive, not as proof of a dose-related difference or a causal relationship.
The study's terminated status is a registry status, not an explanation of why the study ended and not a result. The reason for termination is not reported in the registry record. Overall, the available information supports a description of design and selected safety counts, but it does not support a quantitative conclusion about primary efficacy or a causal comparison among treatment groups.
13. Why This Trial Matters Statistically
This trial raises several important statistical interpretation issues. First, its primary outcome is a time-to-event measure, which depends on both event timing and follow-up. A reported median and confidence interval would be needed to describe the estimated progression-free survival and its precision. The registry record identifies those intended summaries but does not report them, leaving the primary efficacy result unavailable for interpretation.
Second, biomarker-defined cohorts and dose groups in a non-randomized study are not equivalent to randomized comparison arms. Cohort membership may be linked to clinical or disease characteristics, and the registry does not describe an adjusted comparative analysis. This makes it important to distinguish descriptive results within groups from evidence about differences caused by treatment or dose.
Third, open-label, investigator-determined progression assessment raises questions about assessment procedures and potential bias. The registry describes RECIST v1.1 criteria but does not report whether progression was independently reviewed. Finally, the record lists numerous secondary outcomes without reporting their results or a multiplicity strategy. Together, these features make careful separation of the protocol's questions, the available outcomes, and the claims supported by the record essential. The study's status and enrollment do not replace outcome estimates or resolve those design limitations.
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.
Important trial-specific information is absent from the registry record. The reason the study was terminated is not reported, and the record does not explain whether termination affected follow-up or outcome reporting. The primary endpoint's median and 95% confidence interval are not reported, nor is a sponsor-reported hazard ratio. Numerical results for the listed secondary endpoints are also not reported.
The study was non-randomized and open-label. The record does not explain how participants entered the biomarker and dose cohorts, whether assignment criteria changed, or whether an adjusted between-group analysis was planned. The cohort definitions differ by biomarker classification and dose, making direct comparisons vulnerable to confounding. Investigator determination of progression is described, but independent review is not reported.
The registry defines an efficacy population, but its analyzed size is not reported. It does not give numbers of progression events, numbers censored, follow-up summaries, or reasons for missing assessments. The censoring description's reference to randomization is not aligned clearly with the listed non-randomized design. Details on multiplicity, interim analyses, protocol-based sample-size rationale, and sensitivity analyses are not reported in the registry record. These omissions limit assessment of both statistical reliability and the completeness of outcome reporting.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: A Study to Assess the Safety and Efficacy of the VEGFR-FGFR-PDGFR Inhibitor, Lucitanib, Given to Patients With Metastatic Breast Cancer — NCT02202746.
- Registry record last updated 2020-06-23; status last verified 2020-06.
- Results first posted 2020-06-23.
- Data retrieved from ClinicalTrials.gov on 2026-11-09.
- Group sizes, means, event counts and sponsor-reported p-values are reproduced as posted. Effect estimates, confidence intervals and p-values not attributed to the sponsor are independently calculated from the posted summary statistics.
Continue through the Clinical Biostats statistical pathway
Use this trial's endpoint as a starting point for deeper study of effect measures, confidence intervals, and sample-size planning.
18. Record Summary
NCT02202746 is a phase 2, open-label, multicenter, non-randomized study of oral lucitanib in metastatic breast cancer. It enrolled 178 participants, began on 2014-09-09, reached primary completion on 2017-01-17, and is recorded as terminated. The cohorts used biomarker classifications and daily doses of 10 mg or 15 mg. Investigator-assessed progression-free survival by RECIST v1.1 was the primary efficacy endpoint. The registry also lists response, disease-control, and pharmacokinetic outcomes. The primary endpoint estimate, confidence interval, and sponsor-reported hazard ratio are not reported in the registry record. Serious adverse-event counts are reported by dose group, but the non-randomized design does not support treating those groups as like-for-like controls.