Colorectal Cancer Metastatic: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Colorectal Cancer Metastatic (NCT01670721), a na phase 3 study. The primary outcome is Percentage of Participants With Adverse Events (AEs).

2. Clinical Question

The clinical question is consequently descriptive: what adverse events and health-related quality-of-life measurements were recorded among this treated population? The registry record does not establish a comparative question about whether the combination changes outcomes relative to another treatment or to no treatment. Without a control group, observed events cannot be attributed to the study regimen by comparison with a concurrent group. The record describes the treatment context and intended outcomes, but does not report results for the quality-of-life outcomes or an analysis that would quantify change over time.

3. Trial Design

This was a completed, phase 3, multicenter, single-arm, open-label clinical trial sponsored by Sanofi. The registry lists an enrollment of 175. The study began in 2012-08, its primary completion was in 2015-06, and its status is completed. Allocation is listed as not applicable, consistent with the single-group design; masking was none.

Participants received aflibercept with FOLFIRI after previous treatment with an oxaliplatin-containing regimen. The regimen combined aflibercept with irinotecan, 5-fluorouracil, and leucovorin. The registry’s intervention description gives treatment components and administration details, but the record’s displayed regimen description is incomplete. It does not report a separate control arm or a randomized treatment assignment.

The primary objective was safety evaluation. The primary outcome was the percentage of participants with adverse events, assessed from baseline through 30 days after the last administration of either aflibercept or FOLFIRI, whichever came last. The stated maximum exposure was 723 days. The secondary objective was to document health-related quality of life, with outcomes covering change from baseline in EORTC QLQ-C30, EQ-5D-3L index score, and EQ-5D-3L VAS score.

The design can describe the experience of participants treated in the study, including the adverse events recorded during the defined observation period. Because there is no concurrent comparator, it cannot estimate a treatment contrast within this trial. The registry record does not report the protocol’s sample-size justification, the planned statistical analysis, or whether interim analyses were conducted. Those details should not be inferred from the phase designation or the enrollment count.

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.

Before assignment: Participants enrolled in the study to assess the safety of Aflibercept in participants treated with a combination of Aflibercept with FOLFIRI regimen (Irinotecan, Leucovorin and 5-Fluorouracil \[5-FU\]).

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: Safety population defined as the participants who signed the informed consent form and received at least part of one dose of study treatment.

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.

6. Primary Endpoint

The registry lists the primary outcome as Percentage of Participants With Adverse Events (AEs), measured over Baseline upto 30 days after the last treatment administration (either Aflibercept or FOLFIRI whichever comes last) (maximum exposure:723 days).

The primary endpoint is the percentage of participants with adverse events during the defined safety observation period: baseline through 30 days after the last treatment administration, either aflibercept or FOLFIRI, whichever came last. The maximum exposure stated in the record is 723 days. An adverse event was defined as an untoward medical occurrence in a participant who received investigational medicinal product, without requiring the event to be considered causally related to treatment.

The record also defines treatment-emergent adverse events as events that developed or worsened, or became serious, during the on-treatment period. That period ran from the first dose through 30 days after the last dose. Serious adverse events were defined by specified outcomes, including death, a life-threatening event, initial or prolonged inpatient hospitalization, persistent or significant disability or incapacity, congenital anomaly or birth defect, or an event considered medically important. The record says that the treatment-emergent adverse-event measure included participants with both serious and non-serious events.

Using a percentage gives a direct description of how many participants in the safety population experienced events. It is useful for summarizing the frequency of observed safety events in this treated group, but does not by itself show whether treatment caused them. The registry record does not report an overall primary-endpoint analysis beyond the adverse-event counts summarized in its safety information.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

Statistical methods should be interpreted in light of the study question and design. This trial has one treated group, not randomized treatment arms. Its main statistical contribution in the registry is therefore descriptive: counts and percentages of participants with recorded adverse events. A descriptive frequency reports what occurred among participants observed in the study; it is not itself a causal estimate of treatment effect.

What does a participant percentage describe?

For a binary outcome such as whether a participant experienced an adverse event, a percentage summarizes the proportion of participants with the event among those included in the relevant safety population. The registry identifies the safety population as participants who signed informed consent and received at least part of one dose of study treatment. The adverse-event summary lists 175 at risk for serious events and 175 at risk for other events. It records 71 participants with serious adverse events and 172 with other adverse events.

These categories should be read as the registry labels them. The primary endpoint is the percentage of participants with adverse events, and the definition of treatment-emergent adverse events includes participants with both serious and non-serious events. The record does not provide a separate full statistical analysis of the primary endpoint, or explain how overlapping event categories were handled in any overall summary.

Why does the single-group design matter?

A randomized comparison estimates a contrast between groups under the trial’s allocation process. This study has no comparator group, so it cannot estimate such a contrast. The reported event frequencies describe participants receiving aflibercept with FOLFIRI; they do not show how the same population would have fared under a different regimen. General statistical principle: a comparison group can help distinguish treatment-group differences from background risk and other influences, but interpretation also depends on how the groups were formed and analyzed. Here, the registry reports a single group and no randomized comparison.

The open-label design means treatment masking was not used. General statistical principle: when participants and investigators know which treatment is being given, that knowledge can influence reporting, attention to symptoms, or other aspects of assessment. This is relevant to subjective outcomes, including health-related quality of life, though the registry record does not report enough about outcome collection or analysis to assess any such influence in this study.

What would uncertainty measures add?

General statistical explanation: a confidence interval places an estimated quantity in the context of sampling uncertainty, under the assumptions of its method. A point estimate alone does not show how precisely the underlying frequency has been estimated. No confidence intervals are reported in the registry record for the adverse-event figures. The record also does not report a statistical test or a model for those results. No precision claim beyond the reported counts and percentages is warranted.

General statistical explanation: over-dispersion is relevant when a count model assumes less variability than the data contain; it can make standard errors too small if left unaddressed. The primary endpoint is a participant-level event percentage rather than a reported count-rate model. The registry record does not say that a count model, a model for repeated events, or an over-dispersion adjustment was used. It would be inappropriate to infer such methods.

What do the planning illustrations mean?

The sample-size illustrations use a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. They are planning illustrations computed from an observed effect, with the effect to detect defined as a stated fraction of that observed effect. Such figures are hypothetical planning quantities, not observed trial results and not evidence of the study’s achieved power. The illustrations assume two arms, whereas this trial is single-group. The registry record does not report the trial’s own sample-size justification or design assumptions, so the illustrations should not be treated as its protocol or as confirmation that the enrollment was sufficient.

The registry reports zero analyses. The statistical analysis plan, including any handling of missing observations, multiplicity, covariates, or repeated measurements, is not reported in the registry record. No analysis method can be ascribed to the trial beyond the descriptive adverse-event information recorded.

10. Multiplicity, Missing Data and Analysis Populations

The study has a primary safety objective and secondary health-related quality-of-life outcomes. The registry lists three quality-of-life change-from-baseline outcomes: EORTC QLQ-C30, EQ-5D-3L index score, and EQ-5D-3L VAS score. Considering multiple outcomes can raise a multiplicity issue: when several hypotheses are tested, the chance of at least one apparently unusual result can increase. General statistical approaches may define a primary comparison hierarchy or adjust for multiple testing, but the registry record does not report whether any such approach was planned or used.

The registry lists zero analyses and does not report results for the quality-of-life outcomes. It is therefore not possible to assess how missing observations, repeated assessments, or multiple outcome measures were handled. The method for determining which participants contributed to each quality-of-life analysis is not reported in the registry record. No imputation method, sensitivity analysis, or missing-data assumption is reported there.

The safety population is defined as participants who signed informed consent and received at least part of one dose of study treatment. That definition describes the population for safety evaluation; it does not establish the analysis populations used for the secondary outcomes. The registry record does not report any separate analysis-population definitions for the quality-of-life measures or a participant flow through those assessments.

General statistical principle: missing outcome data can affect interpretation when the reasons for missingness are related to participants’ health or their unobserved outcomes. Without counts of missing observations, reasons for missingness, and the planned methods, the direction or magnitude of any resulting uncertainty cannot be assessed. The record also does not report interim analyses or stopping rules. These omissions should be treated as unreported information, not as evidence that such procedures were absent from the full study documentation.

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: disease progression (5.1%), diarrhoea (4.6%), general physical health deterioration (4.6%), pulmonary embolism (2.3%), abdominal pain (1.7%).

The adverse-event summary lists 175 participants at risk for serious adverse events, of whom 71 were recorded as affected. For other adverse events, it lists 175 at risk and 172 affected. These are participant counts in the single treatment group. They are not estimates of excess risk relative to another treatment, because no comparator group is reported.

The serious-event terms are listed separately with percentages: disease progression, 5.1%; diarrhoea, 4.6%; general physical health deterioration, 4.6%; pulmonary embolism, 2.3%; abdominal pain, 1.7%; and intestinal obstruction, 1.7%. These terms describe events recorded in the registry summary. The registry defines serious adverse events using outcomes such as death, a life-threatening event, hospitalization, significant disability or incapacity, congenital anomaly or birth defect, or an event considered medically important. It does not follow from the term being listed that treatment caused the event.

General statistical explanation: participants can experience more than one event, so event categories need not represent mutually exclusive groups. The registry record does not explain the overlap among listed terms in this summary. The counts should therefore be read as reported participant counts, not added together to infer a total number of unique events. No deaths value is reported in the adverse-event summary.

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

The registry record supports a descriptive account of safety outcomes among participants treated with aflibercept and FOLFIRI after previous oxaliplatin-containing treatment. It reports 71 participants with serious adverse events and 172 with other adverse events, each among 175 at risk. It also lists several serious-event terms and their percentages. Those figures convey what was recorded in the study; they do not establish causation or comparative safety.

The record also indicates that health-related quality of life was a secondary objective, measured through EORTC QLQ-C30 and EQ-5D-3L outcomes. However, it does not report results for those outcomes. Consequently, the record does not establish whether quality-of-life scores changed, in which direction they may have changed, or how precisely any change was estimated.

The single-group, open-label design sets important limits. Without a control group, there is no within-trial estimate of how outcomes differ from another treatment or from an untreated comparison. The event frequencies can reflect the participants’ disease, previous treatment, other care, and follow-up as well as treatment exposure. The registry definitions also include events regardless of whether a causal relationship to treatment was considered possible.

These limitations do not make the recorded counts meaningless: they describe adverse events observed in a defined treated population and observation window. They do mean that the counts should not be translated into a claim that treatment caused, prevented, or changed the frequency of an event. No efficacy conclusion should be drawn from the safety information alone. The registry record does not report comparative efficacy results, quality-of-life findings, confidence intervals, or analyses that would support broader claims.

13. Why This Trial Matters Statistically

This trial is statistically notable because it illustrates the difference between documenting outcomes in a treated group and estimating a comparative treatment effect. A single-arm safety study can record adverse events and describe their frequency in the enrolled population. It cannot, by design, provide a randomized comparison of those frequencies against another regimen. That distinction is essential when reading event percentages as evidence about treatment.

The primary endpoint is a participant-level adverse-event measure, with a defined safety population and observation period. Its interpretation depends on the definitions used: the registry includes events without requiring a causal relationship and describes treatment-emergent events over the period from first dose to 30 days after last dose. A clear outcome definition helps explain what is being counted, while the absence of a comparator limits what can be concluded from the count.

The quality-of-life objectives also highlight the importance of complete reporting. The registry identifies three change-from-baseline measures, but reports no results or analyses for them. Without those results, readers cannot assess the magnitude, direction, or precision of any change. The record likewise does not describe multiplicity handling, missing-data methods, or the analysis plan.

The sample-size illustrations require careful separation from the trial design. They use assumptions for a hypothetical two-arm planning exercise, while this study had one group. They are not observed power and do not establish that the original enrollment was based on those assumptions. The protocol’s sample-size justification is not reported in the registry record. The example underscores why planning calculations must be interpreted in the context of the actual design and question, rather than as a retrospective measure of study success.

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 absence of a control group is a central limitation for interpreting the adverse-event frequencies. The study describes outcomes in participants receiving aflibercept with FOLFIRI, but provides no concurrent treatment group for comparison. Consequently, background events and effects of underlying disease or prior care cannot be separated from treatment-associated events using a randomized contrast in this record.

The study was open label, and the registry does not describe methods used to reduce possible influence of treatment awareness on reporting or assessment. This is especially relevant to subjective measures such as health-related quality of life. Although the record lists the instruments and change-from-baseline outcomes, it does not report their results, assessment schedule, or analytic methods.

The registry record reports no analyses. It also does not report confidence intervals, statistical tests, adjustment methods, multiplicity procedures, missing-data methods, interim analyses, or the protocol’s sample-size justification. These omissions prevent assessment of the precision and analytic assumptions underlying the posted safety information and leave the secondary outcomes uninterpretable from the registry record alone.

The safety population is defined, but the record does not report additional analysis populations or participant flow through the quality-of-life assessments. The adverse-event summary lists participant counts and selected event terms, but does not explain overlap among event terms or provide a deaths value. The maximum exposure is stated as 723 days, but the record does not give exposure distributions across participants. These limits mean that the listed findings should be treated as a registry-level description, not a complete account of all trial methods or results.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Colorectal Cancer Metastatic — NCT01670721.
• Registry record last updated 2016-11-28; status last verified 2016-10.
• Results first posted 2016-11-28.
• 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

NCT01670721 is a completed, phase 3, multicenter, single-arm, open-label trial sponsored by Sanofi, with enrollment of 175. It evaluated aflibercept with FOLFIRI in participants with metastatic colorectal cancer previously treated with an oxaliplatin-containing regimen. The primary objective concerned safety; health-related quality of life was a secondary objective.

The primary outcome was the percentage of participants with adverse events during the defined safety period. The adverse-event summary records 71 participants with serious adverse events and 172 with other adverse events, among 175 at risk in each category. Selected serious-event terms are reported with percentages. The registry lists quality-of-life change-from-baseline outcomes but does not report their results or analyses.

Because there is no comparator, the record describes observed events rather than a treatment contrast. The statistical analysis plan, missing-data methods, multiplicity approach, and sample-size justification are not reported in the registry record.