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 of Bevacizumab (Avastin) in Combination With Rituximab (MabThera) and CHOP (Cyclophosphamide, Hydroxydaunorubicin [Doxorubicin], Oncovin [Vincristine], Prednisone) Chemotherapy in Patients With Diffuse Large B-cell Lymphoma (NCT00486759), a randomized phase 3 study. The primary outcome is Progression-free Survival (PFS).
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT00486759 |
| Phase | Phase 3 |
| Condition | B-cell Lymphoma |
| Allocation | Randomized |
| Design model | Parallel |
| Masking | Double |
| Enrollment | 787 |
| Arms in the primary outcome | 2 |
| Lead sponsor | Hoffmann-La Roche |
| Results posted | Yes |
2. Clinical Question
Population
Previously untreated patients with CD20-positive diffuse large B-cell lymphoma (DLBCL). The primary endpoint population is the intent-to-treat population: all randomized patients, whether or not they received their assigned treatment.
Intervention
Bevacizumab added to rituximab and CHOP chemotherapy (R-CHOP). Patients were assigned to receive 8 cycles; the registry describes treatment on either a 2-week or 3-week schedule.
Comparator
Placebo added to rituximab and CHOP chemotherapy. The trial was randomized, double-blind, placebo-controlled, and parallel-group.
Primary question
How did progression-free survival (PFS), measured from randomization until investigator-determined progression or relapse, or death from any cause, compare between the treatment groups? The posted primary results give medians for each group, but a sponsor-reported hazard ratio or other two-arm primary comparison is not reported in the registry record.
The trial also listed overall survival and overall response as secondary outcomes. The registry record posts overall-response results, but an overall-survival result is not reported. The posted evidence therefore answers the primary question only descriptively through the group medians; it does not provide a registry-reported relative time-to-event estimate for comparing the groups.
3. Trial Design
This was a multicenter, randomized, double-blind, placebo-controlled phase III trial with a parallel-group design. It enrolled patients with previously untreated CD20-positive DLBCL. The recorded enrollment was 787. The registry lists the trial status as terminated; the reason for termination is not reported in the registry record.
Patients were assigned to bevacizumab plus rituximab and CHOP, or placebo plus rituximab and CHOP. The treatment plan described 8 cycles. Treatment was administered on either a 2-week or 3-week schedule. The brief description gives bevacizumab as a weekly average dose of 5 mg/kg, with 10 mg/kg for 2-week cycles and 15 mg/kg for 3-week cycles. The arm description lists bevacizumab 5 mg/kg/week on Day 1 of each cycle. Rituximab was listed as 375 mg/m2 intravenously on Day 1 of each cycle in both arms. CHOP comprised cyclophosphamide, doxorubicin, vincristine, and prednisone.
The registry reports 390 patients in the bevacizumab arm and 397 in the placebo arm for the primary endpoint. The primary analysis population is explicitly defined as all randomized patients, regardless of whether assigned treatment was received. This definition is relevant because it preserves the randomized comparison as the basis for the primary endpoint population.
The recorded start date was 2007-07-26, and the primary completion date was 2011-11-30. The primary endpoint timeframe is described as baseline to the end of the study, up to 4 years, 4 months. The registry identifies Hoffmann-La Roche as sponsor. Details of allocation concealment, stratification, protocol deviations, and the reason the trial was terminated are not reported in the registry record.
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.
Treatment
| Stage | Bevacizumab + Rituximab + CHOP | Placebo + Rituximab + CHOP |
|---|---|---|
| STARTED | 390 | 397 |
| COMPLETED | 203 | 260 |
| NOT COMPLETED | 187 | 137 |
Reasons for not completing this period:
| Reason | Bevacizumab + Rituximab + CHOP | Placebo + Rituximab + CHOP |
|---|---|---|
| Adverse event/intercurrent illness | 86 | 39 |
| Insufficient therapeutic response | 37 | 39 |
| Death | 17 | 10 |
| Withdrew consent | 15 | 12 |
| Administrative/reason not specified | 17 | 21 |
| Refused treatment | 10 | 7 |
| Violation of selection criteria at entry | 3 | 3 |
| Other protocol violation | 1 | 5 |
| Failure to return | 1 | 1 |
Safety Follow-up
| Stage | Bevacizumab + Rituximab + CHOP | Placebo + Rituximab + CHOP |
|---|---|---|
| STARTED | 203 | 260 |
| COMPLETED | 64 | 142 |
| NOT COMPLETED | 139 | 118 |
Reasons for not completing this period:
| Reason | Bevacizumab + Rituximab + CHOP | Placebo + Rituximab + CHOP |
|---|---|---|
| Insufficient therapeutic response | 40 | 50 |
| Death | 40 | 29 |
| Withdrew consent | 32 | 23 |
| Failure to return | 9 | 6 |
| Administrative/not specified | 8 | 6 |
| Refused treatment/did not cooperate | 6 | 4 |
| Adverse event/intercurrent illness | 4 | 0 |
Analysis population for the primary outcome, as defined in the registry: Intent-to-treat population: All randomized patients, regardless whether or not they had actually received the assigned treatments.
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 | Bevacizumab + Rituximab + CHOP | Placebo + Rituximab + CHOP | Total |
|---|---|---|---|---|
| Participants analysed | 390 | 397 | 787 | |
| Age, Continuous | years | 57.89 (SD 14.256) | 56.98 (SD 15.399) | 57.44 (SD 14.841) |
| Sex: Female, Male: Female | Participants | 207 | 193 | 400 |
| Sex: Female, Male: Male | Participants | 183 | 204 | 387 |
6. Primary Endpoint
The registry lists the primary outcome as Progression-free Survival (PFS), measured over Baseline to end of the study (up to 4 years, 4 months).
| Element | Registry entry |
|---|---|
| Result type | Median |
| Measure of spread | Inter-Quartile Range |
| Unit | Months |
| Endpoint classification | Time-to-Event Analysis |
The primary endpoint was progression-free survival (PFS), reported in months as a median. PFS began at randomization and ended at the earlier of investigator-determined disease progression or relapse, or death from any cause. This endpoint combines disease worsening and death into a time-to-event measure, rather than counting only one type of outcome.
The registry's progression criteria include new lesions, increases in the size of previously involved nodes or other lesions, and specified increases in measured disease. The criteria use lesion dimensions and changes from the lowest recorded measurement. The endpoint therefore depends in part on disease assessments and the investigator's determination of progression or relapse.
General: time-to-event endpoints are useful when the timing of an event matters and participants may have different lengths of observation. A median describes the point by which half of the observed event-time distribution has occurred, under the analysis method used. It does not by itself show how the full event-time distributions compare, nor does it quantify the relative event rate between groups.
The registry gives a median for each arm and lists interquartile range as the dispersion measure, but the posted dispersion information is incomplete. A sponsor-reported hazard ratio, confidence interval for the primary comparison, and primary comparison p-value are not reported in the registry record. Those missing estimates limit the precision with which the relative PFS result can be interpreted.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The posted median PFS was 40.2 months in the bevacizumab plus R-CHOP arm and 42.9 months in the placebo plus R-CHOP arm. These are descriptive group medians. The registry record does not post a sponsor-reported hazard ratio or other inferential comparison for this primary time-to-event endpoint, so the medians alone do not establish the size or statistical precision of a between-group difference.
The registry identifies interquartile range as the dispersion measure, but reports only one bound for each arm: 12.1 months for bevacizumab plus R-CHOP and 13.6 months for placebo plus R-CHOP. The corresponding upper bounds are not reported in the registry record. Without the full spread information or a primary comparison estimate, it is not possible to assess the uncertainty around the medians from the posted primary result alone.
Overall response is a secondary endpoint. Its posted group percentages are 63.1% with bevacizumab plus R-CHOP and 70.5% with placebo plus R-CHOP. A recalculated, unadjusted risk difference for bevacizumab versus placebo is -0.074, with a confidence interval from -0.140 to -0.009 and p = 0.026. This recalculation uses the posted summary counts and is not identified as a sponsor-reported analysis. It is an unadjusted comparison; it should not be treated as the primary PFS result or as evidence that accounts for testing multiple outcomes.
The registry lists overall survival as a secondary outcome, but an overall-survival result is not reported in the registry record. That absence means the listed outcome cannot contribute a posted estimate of survival differences. It also prevents a comparison between the response result and longer-term survival results from this record.
Read together, the posted primary medians are numerically higher in the placebo arm, and the posted overall-response comparison is also numerically less favorable in the bevacizumab arm. These observations describe the registry results; they do not establish a treatment effect. The primary endpoint lacks a reported comparative estimate, and the secondary comparison is unadjusted. The registry record also does not provide enough information to judge whether the observed pattern was consistent across other outcome analyses or how missing observations were handled.
9. Statistical Methods Explained
The trial used random assignment and double masking in a parallel-group comparison. Randomization is intended to make treatment groups comparable on average at the start of a trial, while masking can reduce the influence of treatment knowledge on care and assessment. These are general design principles; the specific randomization procedure, allocation concealment, masking implementation, and assessment safeguards are not reported in the registry record.
What does the primary median represent?
PFS is a time-to-event outcome. Each participant's recorded time runs from randomization to progression or relapse, as determined by the investigator, or death from any cause, whichever occurs first. The posted medians are summaries of the event-time distributions in the two arms. A median is not the same as an average, and it does not describe all of the follow-up experience or how the event rate changes over time.
General: survival analysis methods can account for participants whose event has not been observed by the end of their available follow-up, a situation commonly described as censoring. The registry record does not report the censoring rules, the specific method used to estimate the median, or details of follow-up completeness. It also does not post a sponsor-reported hazard ratio, confidence interval, or p-value for the primary endpoint. Consequently, the posted median values do not provide a complete inferential comparison.
Why do the missing dispersion details matter?
The registry names interquartile range as the dispersion measure for PFS. For the bevacizumab arm, 12.1 months is listed as a bound; for the placebo arm, 13.6 months is listed. The other bound for each arm is not reported in the registry record. A measure of spread helps describe how event times vary across participants. Without the full reported spread, and without a confidence interval for the median or a comparative time-to-event estimate, the precision of the posted primary medians cannot be evaluated fully.
General: a hazard ratio, when reported, compares the event rate over time between groups under the assumptions of the fitted model. It is not interchangeable with a difference between medians. No sponsor-reported hazard ratio is available in this record, so a relative time-to-event estimate should not be inferred from the medians.
How should the response comparison be read?
Overall response is a binary outcome: participants are classified according to whether they met the response definition by the specified assessment time. The registry posts the response percentages and counts for each group. The recalculated risk difference is an unadjusted contrast derived from those posted summary counts. Its confidence interval describes uncertainty under that simple comparison, and the unadjusted p-value evaluates the contrast without adjustment for other tested outcomes.
General: a confidence interval gives a range of values compatible with the data under the analysis assumptions; it is not a guarantee that the true value lies within that range. A p-value measures how incompatible the observed data are with a specified null model, assuming that model and analysis are appropriate. Neither quantity alone establishes clinical importance or resolves potential bias, missing data, or multiplicity.
The registry reports no sponsor-reported analyses for the posted secondary comparison. The recalculation should therefore be kept distinct from a trial sponsor's planned or reported analysis. The discrepancy indicator is false, but that does not change the fact that the comparison is a recalculation rather than a posted sponsor analysis.
What do the sample-size illustrations represent?
The sample-size illustrations are planning calculations based on fractions of the observed effect, with a two-sided significance level of 0.05, equal allocation, and a normal approximation. The listed calculations describe participants per arm for the stated power targets and effect assumptions. They are illustrations based on the observed response effect, not the original trial's design justification and not observed power. The registry record does not report the original sample-size justification or its assumptions.
General: planning calculations estimate how much information a future study might need under specified assumptions. They do not measure the probability that the completed trial's result is true, and they do not alter the uncertainty of the results already observed. Because the illustrations use an observed effect as their starting point, different assumed effect sizes yield different planning requirements; the values are not a retrospective measure of this trial's success.
What analysis population is specified?
For the primary endpoint, the registry defines the intent-to-treat population as all randomized patients, regardless of whether assigned treatment was actually received. This makes the primary population definition explicit. The registry record does not report the handling of missing endpoint observations, deviations from assigned treatment, or details of analysis populations for the secondary outcomes. Those details matter because the included observations and assumptions about missingness can affect estimates and their uncertainty.
10. Multiplicity, Missing Data and Analysis Populations
The primary analysis population is explicitly defined as intent-to-treat: all randomized patients, irrespective of whether they received their assigned treatment. That definition clarifies who was intended to contribute to the primary endpoint analysis. The registry record does not provide corresponding detail about the analysis populations used for the secondary outcomes.
Overall survival is listed as a secondary outcome, but its result is not reported in the registry record. The registry posts overall-response data and a recalculated unadjusted comparison, but does not report sponsor analyses for that comparison. A multiplicity adjustment or other strategy for interpreting multiple outcomes is not reported in the registry record. Without that information, the unadjusted secondary p-value should not be read as if it were adjusted for the set of outcomes considered.
Missing-data procedures are not reported in the registry record. This includes how missing PFS assessments, incomplete follow-up, or unavailable response assessments were handled. The registry does not state whether participants with missing outcome information were excluded, censored, or handled using another approach. Those choices can affect estimates, especially when missingness is related to participants' outcomes or treatment experience.
The record also does not report the primary statistical analysis plan, interim analyses, or the original sample-size justification. The posted sample-size illustrations are planning calculations based on the observed response effect and stated assumptions; they are not evidence of the trial's original planning process or of observed power. The status is recorded as terminated, but the reason for termination is not reported in the registry record. These omissions limit assessment of prespecification, selective reporting, and the relationship between the registry results and the trial's intended analyses.
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 |
|---|---|---|---|
| Bevacizumab + Rituximab + CHOP | 224 | 395 | 56.7% |
| Placebo + Rituximab + CHOP | 173 | 386 | 44.8% |
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 |
|---|---|
| Bevacizumab + Rituximab + CHOP | 346 of 395 |
| Placebo + Rituximab + CHOP | 331 of 386 |
Most frequent serious adverse event terms
| Event term | Organ system | Bevacizumab + Rituximab + CHOP | Placebo + Rituximab + CHOP |
|---|---|---|---|
| Febrile neutorpenia | Blood and lymphatic system disorders | 63 of 395 | 48 of 386 |
| Pneumonia | Infections and infestations | 22 of 395 | 16 of 386 |
| Neutropenia | Blood and lymphatic system disorders | 12 of 395 | 17 of 386 |
| Pyrexia | General disorders | 14 of 395 | 15 of 386 |
| Left ventricular dysfunction | Cardiac disorders | 15 of 395 | 5 of 386 |
| Leukopenia | Blood and lymphatic system disorders | 6 of 395 | 5 of 386 |
| Septic shock | Infections and infestations | 6 of 395 | 4 of 386 |
| Cardiac failure | Cardiac disorders | 6 of 395 | 4 of 386 |
| Anaemia | Blood and lymphatic system disorders | 8 of 395 | 1 of 386 |
| Thrombocytopenia | Blood and lymphatic system disorders | 5 of 395 | 4 of 386 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Bevacizumab + Rituximab + CHOP | Placebo + Rituximab + CHOP |
|---|---|---|---|
| Nausea | Gastrointestinal disorders | 107 of 395 | 106 of 386 |
| Neutropenia | Blood and lymphatic system disorders | 88 of 395 | 119 of 386 |
| Diarrhoea | Gastrointestinal disorders | 95 of 395 | 81 of 386 |
| Alopecia | Skin and subcutaneous tissue disorders | 96 of 395 | 80 of 386 |
| Anaemia | Blood and lymphatic system disorders | 66 of 395 | 96 of 386 |
| Constipation | Gastrointestinal disorders | 88 of 395 | 70 of 386 |
| Fatigue | General disorders | 71 of 395 | 71 of 386 |
| Vomiting | Gastrointestinal disorders | 56 of 395 | 70 of 386 |
| Pyrexia | General disorders | 71 of 395 | 55 of 386 |
| Asthenia | General disorders | 59 of 395 | 60 of 386 |
Serious events with the highest arm-level rate: febrile neutorpenia (15.9%), pneumonia (5.6%), neutropenia (4.4%), pyrexia (3.9%), left ventricular dysfunction (3.8%).
The registry reports serious adverse events in 224 of 395 participants in the bevacizumab plus R-CHOP group and 173 of 386 participants in the placebo plus R-CHOP group. It also reports other adverse events in 346 of 395 and 331 of 386 participants, respectively. These are descriptive counts with their recorded group denominators; they do not by themselves establish that treatment caused an event or quantify a comparative safety effect.
The listed serious adverse-event terms include febrile neutorpenia at 15.9%, pneumonia at 5.6%, neutropenia at 4.4%, pyrexia at 3.9%, left ventricular dysfunction at 3.8%, and anaemia at 2.0%. The registry record does not clarify the denominator or arm context for this term list, so those percentages should not be assigned to a specific treatment group from the posted information alone. Death counts are not reported in the registry record.
General: adverse-event counts can depend on the observation period, definitions, and rules for recording events. A descriptive comparison does not account for differences in exposure or provide a causal estimate. The registry record does not report enough detail to evaluate those considerations or to make a complete comparative safety assessment.
12. What the Result Does, and Does Not, Mean
The primary result describes median PFS in each randomized group. The posted values are close in numerical terms, with the placebo arm's median higher. However, the registry record does not provide a sponsor-reported hazard ratio, confidence interval, or p-value for the primary comparison. The posted medians therefore do not establish whether the groups differed beyond the observed descriptive values, or how precisely any difference was estimated.
The secondary response comparison is an unadjusted recalculation from posted summary counts. It is not a substitute for the missing primary comparative analysis, and it does not address the registry's lack of an overall-survival result. The record does not report whether secondary analyses were adjusted for multiple outcomes, how missing data were handled, or whether the reported comparisons followed a prespecified statistical plan.
General: statistical evidence and clinical importance are different questions. An estimate describes the observed contrast under an analysis, while its uncertainty indicates how much the data leave open. Whether a difference matters clinically requires context beyond a p-value or a group median. No medical recommendation follows from these registry results.
The results also do not show what would happen for every patient. Group summaries describe the trial population and analysis, not an individual outcome. The primary endpoint included investigator-determined progression or relapse, as well as death from any cause, and the record does not provide details of independent endpoint review or missing-assessment procedures.
The trial status is terminated, but the reason is not reported in the registry record. That status alone does not explain the posted results or indicate why the trial ended. Overall, the record supports a cautious descriptive reading of the arm-specific PFS medians and a separate, unadjusted reading of the response comparison, with substantial limits on formal inference from the primary endpoint.
13. Why This Trial Matters Statistically
This trial is statistically notable because the registry combines a randomized, double-blind phase III design with incomplete reporting of the primary comparative analysis. Randomization and masking are important design features, but they do not remove the need for an estimate of the between-group effect and its uncertainty. Arm-specific medians provide a useful description, yet they cannot replace a comparative time-to-event analysis.
The case also illustrates why endpoint definitions and analysis populations matter. PFS combines progression or relapse determined by the investigator with death from any cause, and the primary population is defined as all randomized patients. Those details clarify what outcome and population the posted result is intended to represent. In contrast, censoring rules, missing-data procedures, full dispersion information, and a primary hazard ratio are not reported in the registry record.
The secondary response comparison shows another statistical issue: an unadjusted result has to be interpreted in the context of other outcomes. Overall survival is listed but has no posted result, while the primary comparative estimate is absent. The record does not state a multiplicity strategy, so the secondary p-value cannot be treated as though it were protected against the risks of examining multiple outcomes.
The sample-size illustrations are also distinct from trial design evidence. They are planning examples based on the observed response effect, not observed power and not a record of the original sample-size justification. Separating descriptive estimates, recalculations, and planning calculations helps prevent them from being mistaken for one another. This trial therefore demonstrates how a registry can contain meaningful design and endpoint information while still leaving key questions about estimation, precision, and analysis methods unresolved.
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 main limitation of the posted efficacy record is the absence of a sponsor-reported comparative analysis for the primary PFS endpoint. Medians are available for each arm, but the registry does not report a hazard ratio, confidence interval, or p-value for that endpoint. The interquartile-range information is incomplete: one bound is listed for each arm, while the other is not reported in the registry record.
The registry defines progression using investigator determination and detailed lesion criteria, but does not report whether progression assessments were independently reviewed. It does not report censoring rules, follow-up completeness, or how missing endpoint information was handled. The timeframe is given as up to 4 years, 4 months, but the registry does not provide further follow-up detail for interpreting the observed time-to-event distributions.
For the secondary outcomes, overall survival is listed without a posted result. The overall-response comparison is a recalculation from posted summary counts, and sponsor-reported analyses are absent. A multiplicity plan is not reported. These omissions limit the ability to assess whether secondary findings were prespecified, how they relate to the full set of outcomes, or how missing observations influenced the comparisons.
The record says the trial was terminated but does not report why. It does not provide the original sample-size justification, interim-analysis details, or the full statistical analysis plan. These limits prevent a thorough assessment of the relationship between planned and reported analyses. They do not, by themselves, establish why information is absent or indicate a particular direction of bias.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: A Study of Bevacizumab (Avastin) in Combination With Rituximab (MabThera) and CHOP (Cyclophosphamide, Hydroxydaunorubicin [Doxorubicin], Oncovin [Vincristine], Prednisone) Chemotherapy in Patients With Diffuse Large B-cell Lymphoma — NCT00486759.
- Registry record last updated 2017-07-25; status last verified 2017-06.
- Results first posted 2012-12-31.
- 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
NCT00486759 was a multicenter, randomized, double-blind, placebo-controlled phase III trial in previously untreated patients with CD20-positive DLBCL. It compared bevacizumab plus rituximab and CHOP with placebo plus rituximab and CHOP, with 8 cycles described. Recorded enrollment was 787, and trial status is terminated.
The primary endpoint was PFS from randomization to investigator-determined progression or relapse, or death from any cause. Median PFS was 40.2 months in the bevacizumab arm and 42.9 months in the placebo arm. A sponsor-reported primary comparison is not reported in the registry record. Overall response is posted as a secondary outcome; overall survival is listed but has no reported result. The registry also posts adverse-event counts, but the available information does not provide a complete comparative safety analysis. The reason for termination and key statistical analysis details are not reported in the registry record.