A Study of Avastin (Bevacizumab) in Combination With mFOLFOX-6 or FOLFOXIRI in Patients With Metastatic Colorectal Cancer.: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for A Study of Avastin (Bevacizumab) in Combination With mFOLFOX-6 or FOLFOXIRI in Patients With Metastatic Colorectal Cancer. (NCT00778102), a randomized phase 2 study. The primary outcome is Percentage of Participants With Complete Resection or Residual (Microscopic or Macroscopic) Tumor.

2. Clinical Question

The trial was designed to compare resection and surgical safety between the two first-line treatment strategies in people whose liver metastases were initially considered unresectable. The primary endpoint is a set of residual-tumor classifications rather than a single yes-or-no comparison. R0 denotes complete resection; R1 and R2 describe microscopic and macroscopic residual tumor, respectively. The registry describes percentages for each classification, but does not report the arm-specific estimates or a direct comparison of the groups in the record.

The registry lists secondary outcomes covering time to resection, histopathological response, relapse after curative resection, relapse-free survival, progression, progression-free survival and death. These outcomes address different stages of the treatment and follow-up pathway. Their presence in the record does not establish that results for them are reported. Arm-specific estimates and comparative results for these secondary outcomes are not reported in the registry record.

3. Trial Design

The registry describes OLIVIA as a multicentre, randomized phase II study with a parallel-group design and no masking. Its official title frames the study around safety and resectability in patients with initially unresectable liver metastases secondary to colorectal cancer. The stated treatment setting is first-line therapy. The registry lists an enrollment of 80 and the trial status as completed.

Participants were assigned to bevacizumab with mFOLFOX-6 or bevacizumab with FOLFOXIRI. The brief summary describes the chemotherapy regimens as differing by the inclusion of irinotecan in FOLFOXIRI. It describes bevacizumab at 5 mg/kg intravenously every 2 weeks. The arm descriptions in the registry record are blank, so additional arm-specific details beyond the summary are not reported in the registry record.

The brief summary says treatment was anticipated to continue until surgery, disease progression, unacceptable toxicity or patient refusal. The primary endpoint timeframe is described as up to 5 years, with assessments at screening, every 6 weeks, within 4 weeks before surgery, and at the time of or after surgery. These timepoints describe the stated assessment schedule; they do not establish how many participants completed each assessment.

The registry lists a target sample size of less than 100 individuals in the brief summary, as well as enrollment of 80. A sample-size justification, assumptions used to design the trial, and any planned interim analyses are not reported in the registry record. The randomization method and allocation-concealment procedures are also not reported. No masking was used, according to the registry.

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: ITT Population

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: Intent-to-Treat (ITT) Population: All randomized participants. Participants were analyzed according to which treatment group they were randomized, regardless of the treatment actually received.

6. Primary Endpoint

The registry lists the primary outcome as Percentage of Participants With Complete Resection or Residual (Microscopic or Macroscopic) Tumor, measured over Up to 5 years (at Screening; every 6 weeks, and within 4 weeks prior to surgery; and at time of/after surgery).

The primary endpoint records the percentage of participants classified after resective surgery as having complete resection (R0), microscopic residual tumor (R1), or macroscopic residual tumor (R2). The registry describes calculating each percentage from the number of participants in the relevant classification and the total number of participants. It identifies the analysis population as the ITT Population and gives a timeframe of up to 5 years.

This endpoint is used to describe the surgical result in a population whose liver metastases were initially considered unresectable. The categories distinguish complete removal from the presence and extent of residual tumor. Reporting categories separately can preserve clinically relevant distinctions that would be lost by combining them into a single outcome. It also means that a reader needs the category-specific estimates and their uncertainty to understand the distribution of results.

The registry states that 95% confidence intervals were calculated for one-sample binomial proportions using the Clopper-Pearson method. These intervals describe uncertainty around a proportion within a group. They do not, by themselves, establish the size or statistical uncertainty of a difference between the randomized groups. The arm-specific endpoint percentages, confidence intervals and comparative estimate are not reported in the registry record. Accordingly, the endpoint definition is available, but the primary result cannot be interpreted from the record details.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry identifies a randomized, parallel-group design without masking. Randomization is intended, as a general statistical principle, to make assigned groups comparable on average at the start of a trial. It does not guarantee that every observed characteristic will be balanced, and the registry entries do not describe the randomization sequence or concealment procedures. With no masking, participants and clinical staff were not masked to group assignment according to the registry. Whether outcome assessors were masked is not reported in the registry record.

What does the primary endpoint estimate?

The primary endpoint is expressed as a percentage for each residual-tumor classification following surgery. The registry defines R0 as complete resection and identifies R1 and R2 as microscopic and macroscopic residual tumor. For each classification, the stated calculation uses the number of participants in that category divided by the total number of participants, multiplied by 100. This is a binomial-proportion framework: each participant either falls into the particular category being counted or does not.

That framework is useful for describing how often a defined outcome occurs in a group. It depends on a clear numerator and denominator. The registry specifies the classification and refers to the total number of participants, but does not report the category counts, the calculated percentages, or further details about denominator handling. In particular, the record does not explain the handling of participants who did not undergo resection or lacked an evaluable classification.

What does a confidence interval add?

General explanation: a confidence interval expresses the uncertainty around an estimate that could arise from sampling variation. A narrower interval indicates greater precision under the method’s assumptions; a wider interval indicates less precision. An interval is not a guarantee that the true value lies within its limits, and it does not describe the range of outcomes for individual participants.

The registry states that 95% confidence intervals for the primary proportions were calculated using the Clopper-Pearson method for a one-sample binomial proportion. This is an exact binomial interval method. It is intended for uncertainty around a single proportion, rather than a direct interval for the difference between the randomized groups. The registry does not provide the calculated intervals, so their width and the precision of the primary estimates cannot be assessed from the record details.

How should group comparisons be assessed?

A comparison between randomized groups requires an estimate that directly contrasts the groups, with uncertainty appropriate to that contrast. General explanation: separate confidence intervals around two group-specific estimates do not replace a confidence interval for the between-group difference. A direct comparison can also account for the endpoint’s structure and any prespecified analysis choices. The registry record does not report a primary comparative estimate, a hypothesis test, or a statistical model for comparing the endpoint categories.

The primary outcome involves several categories, and the registry note says it is not reduced to one comparison. This prevents treating the endpoint as though the record posted one binary result. No category-specific results should be inferred from the endpoint definition alone. The secondary outcome list includes both percentages and time-to-event outcomes, but their analysis methods and results are not reported in the registry record.

What do the planning assumptions mean?

The registry’s planning-illustration description specifies a two-sided significance level of 0.05, equal allocation between groups and a normal approximation. It describes the effect to detect as a stated fraction of the observed effect. For time-to-event illustrations, the described quantity is the total number of events; other illustrations are described as participants per arm. These are planning assumptions, not observed trial findings and not observed power. The corresponding calculated sample-size values are not reported in the registry record details. A sample-size illustration cannot establish whether the completed trial had adequate precision for its actual endpoint results.

A trial’s original design justification is distinct from a retrospective planning illustration. The sample-size justification used for this trial, any design alternatives considered, and the assumptions underlying the original enrollment target are not reported in the registry record. The registry also does not describe interim analyses or stopping rules. These omissions mean that the planning description cannot be used to reconstruct the trial’s original statistical plan.

Why can over-dispersion matter?

General explanation: a binomial model assumes a fixed probability of the outcome for the observations being analyzed and independence between observations. If outcomes vary more than the model allows, uncertainty may be understated; this is one reason analysts consider over-dispersion in settings where the binomial assumptions may not fit. The primary endpoint is described using a one-sample binomial method, but the registry does not report an assessment of over-dispersion. Nor does the record indicate that such an assessment was planned. This general consideration should not be mistaken for evidence that over-dispersion occurred in this trial.

10. Multiplicity, Missing Data and Analysis Populations

The primary endpoint contains multiple residual-tumor classifications: R0, R1 and R2. The registry note states that the outcome has several categories or time points and is not reduced to one comparison. When several outcomes or comparisons are examined, multiplicity can matter because the chance of at least one apparently unusual result may increase as the number of tests grows. This is a general statistical concern, not evidence that a particular adjustment was required or performed in this trial.

A multiplicity strategy, including whether any adjustment or hierarchy was planned for primary categories and secondary outcomes, is not reported in the registry record. The record lists 14 outcome measures and 3 analyses, but does not describe how these were organized into confirmatory or exploratory tests. It also does not report a complete statistical analysis plan or identify which comparisons, if any, were prespecified.

The primary outcome description identifies the ITT Population. General explanation: intention-to-treat analysis usually retains participants in their randomized groups and can preserve the benefits of random allocation. The registry does not explain how participants with missing endpoint assessments, no surgery, or an unclassifiable surgical result were handled, nor does it state whether any other analysis population was used.

Missing-data methods, reasons for missing assessments, and the extent of missingness are not reported in the registry record. The record also does not describe imputation, sensitivity analyses, or assumptions about unavailable outcomes. These details matter because an estimate based on assessed participants can be affected if missingness is related to prognosis or treatment experience. No direction or size of such an effect can be inferred without the missing-data information and results.

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: diarrhoea (15.0%), febrile neutropenia (15.0%), neutropenia (10.0%), wound dehiscence (7.5%), pulmonary embolism (5.4%).

The registry lists serious adverse event risk sets of 37 for bevacizumab plus mFOLFOX-6 and 40 for bevacizumab plus FOLFOXIRI. It reports 24 participants affected by serious adverse events in each group. For other adverse events, the listed risk sets are 37 and 40, with 36 and 40 participants affected, respectively. These are counts of participants recorded as affected, not counts of all individual events.

The registry lists diarrhoea and febrile neutropenia at 15.0% each, neutropenia at 10.0%, wound dehiscence at 7.5%, and pulmonary embolism and deep vein thrombosis at 5.4% each among the top serious terms. The record does not provide an arm-specific breakdown for these listed term percentages, so they should not be attributed to either group separately. Death counts are not reported in the registry record.

Safety counts describe what was recorded in the trial; by themselves they do not establish that a treatment caused an event or allow a complete comparison of safety between groups. The registry entries do not specify event severity grading beyond the serious-event classification, exposure-adjusted rates, or the timing and duration of follow-up for each safety event. The figures should therefore be read as descriptive counts and percentages, with those reporting limits in mind.

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

The registry establishes that OLIVIA was a randomized phase II study comparing bevacizumab with mFOLFOX-6 against bevacizumab with FOLFOXIRI in patients with initially unresectable liver metastases from colorectal cancer. It also defines a primary endpoint focused on residual tumor classification after surgery and identifies the ITT Population. These details explain the clinical and statistical question the trial was intended to address.

The record does not report the arm-specific primary endpoint percentages, their confidence intervals, or a direct comparison. It therefore does not show the distribution of complete, microscopic residual, or macroscopic residual tumor across the groups, nor how precisely any group difference was estimated. The endpoint definition and the study’s completed status cannot fill that gap. No conclusion about comparative resection outcomes can be drawn from these record details alone.

The safety section gives counts for participants affected by serious and other adverse events, and percentages for several serious-event terms. Those figures offer descriptive safety information, but the listed term percentages are not assigned to individual arms in the record. The deaths entry is not reported in the registry record. These constraints prevent a full arm-by-arm interpretation of safety or a causal conclusion about the listed events.

The registry lists secondary measures involving response, relapse, progression, time to resection and death. Listing an outcome is not the same as reporting its estimate, uncertainty or comparison. Those results are not reported in the registry record details. The study should therefore be understood as a trial with a defined comparative aim, rather than as evidence for a particular direction or size of effect.

General interpretation: estimates and their uncertainty are both needed to distinguish a potentially meaningful pattern from one that is imprecise. Without the results, the size, direction and precision of the primary comparison remain unknown. This is a limit on what can be concluded from the registry record, not a finding that the treatments were equivalent or that no difference existed.

13. Why This Trial Matters Statistically

This trial raises a statistical question that is more detailed than a single success-versus-failure comparison. The primary outcome separates complete resection from microscopic and macroscopic residual tumor. Keeping those categories distinct can make the result more informative, but it also requires results for each category and a clear account of how comparisons are handled. A lone headline percentage would not fully describe the endpoint as defined in the registry.

The randomized parallel-group design gives the study a framework for comparing treatment strategies. However, the value of randomization for interpretation depends on transparent reporting of the outcome estimates, denominators, uncertainty and analysis decisions. The registry identifies the ITT Population and the Clopper-Pearson method for one-sample proportions, but does not report the primary estimates or a direct contrast between groups. This illustrates why an outcome definition and a statistical method are not substitutes for results.

The study also links surgical outcomes with a range of secondary measures, including histopathological response, relapse, progression and survival outcomes. These measures concern different events and time structures; their estimates require methods suited to each outcome. The record lists the outcomes but does not report their analysis methods or results. Readers should not infer a common effect across endpoints from the fact that they appear in the same trial record.

For biostatisticians and clinical researchers, the record highlights the importance of prespecifying how multiple categories and outcomes will be interpreted, and of reporting missing-data handling and analysis populations. Those details affect how estimates can be understood and compared. In this case, the registry supplies some endpoint-method information but leaves key elements of the statistical plan and findings unreported. That distinction is central to a disciplined reading of clinical-trial evidence.

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 most important limitation for interpreting this registry record is the absence of arm-specific primary endpoint estimates and a direct comparison. The endpoint is defined in detail, including its R0, R1 and R2 categories, but the category counts, percentages and confidence intervals are not reported in the record. As a result, neither the direction nor precision of a primary treatment-group contrast can be assessed.

The registry identifies the ITT Population, but does not describe how participants without surgery or without an assessable residual-tumor classification were handled. Missing-data extent, reasons and methods are not reported. The primary endpoint’s stated denominator therefore cannot be reconstructed from the record details.

The safety information is also limited. Serious and other adverse-event counts are reported with risk sets, but the registry does not provide an arm-specific distribution for the listed serious-event term percentages. Death counts are not reported in the registry record. Further information about event timing, exposure and severity grading is not included in these details, limiting comparative interpretation.

Finally, the registry does not report the full statistical analysis plan, the rationale for the original sample-size target, any interim analyses, or the approach to multiplicity. The record’s planning-illustration assumptions do not substitute for those design details or for observed endpoint results. These limitations concern what can be interpreted from the registry record; they do not establish that an unreported analysis was not conducted.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: A Study of Avastin (Bevacizumab) in Combination With mFOLFOX-6 or FOLFOXIRI in Patients With Metastatic Colorectal Cancer. — NCT00778102.
• Registry record last updated 2016-11-02; status last verified 2016-11.
• Results first posted 2015-08-07.
• 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

OLIVIA is listed as a completed, multicentre randomized phase II study with a parallel design and no masking. It enrolled 80 participants and compared bevacizumab with mFOLFOX-6 against bevacizumab with FOLFOXIRI for first-line treatment of initially unresectable liver metastases secondary to colorectal cancer.

The primary endpoint was the percentage of participants classified after surgery as R0, R1 or R2, with 95% confidence intervals described using the Clopper-Pearson method. The primary analysis population is identified as ITT. The registry record does not report arm-specific primary estimates or a direct comparison.

Safety counts are listed for serious and other adverse events, alongside percentages for selected serious-event terms. Secondary outcomes are listed, but their results are not reported in the registry record details. The statistical analysis plan, missing-data handling and multiplicity approach are also not reported.