Bevacizumab, Temozolomide, and External Beam Radiation Therapy as First-Line Therapy in Treating Patients With Newly Diagnosed Glioblastoma Multiforme or Gliosarcoma: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Bevacizumab, Temozolomide, and External Beam Radiation Therapy as First-Line Therapy in Treating Patients With Newly Diagnosed Glioblastoma Multiforme or Gliosarcoma (NCT01013285), a na phase 2 study. The primary outcome is Overall Survival.

2. Clinical Question

The study also lists time to disease progression, progression-free survival at 6 months, radiographic response when evaluable, and median overall survival according to MGMT promoter methylation status as secondary outcomes. These outcomes describe different aspects of disease course and response. Their names alone do not establish what results were observed or how precisely they were estimated. The registry record does not report the specific eligibility criteria, treatment schedule, or definitions used for these measures. The central statistical distinction is that this is a single-group study: any observed outcome describes the treated group, rather than a contrast between randomly assigned treatment strategies.

3. Trial Design

This is a phase II study recorded as completed. Its title and purpose describe first-line treatment for patients with newly diagnosed glioblastoma multiforme or gliosarcoma, using bevacizumab together with temozolomide and external beam radiation therapy. The registry lists Jonsson Comprehensive Cancer Center as sponsor and an enrollment of 70. The recorded study start is 2006-06 and primary completion is 2013-10.

The design is single group, with allocation recorded as not applicable and masking recorded as none. One arm is listed, containing bevacizumab, temozolomide, and external beam radiation. No concurrent control arm is recorded. Therefore, outcomes in this study cannot be interpreted as a randomized estimate of the difference between the combination and another treatment. A comparison with outcomes from another group would require information beyond this record and would not remove the limitations of a non-randomized comparison.

The primary outcome is overall survival, specified as a median in months with a 95% confidence interval and a timeframe of 2 years. The registry lists five outcome measures and names several secondary outcomes, including progression, progression-free survival at 6 months, radiographic response when evaluable, and overall survival by MGMT promoter methylation status. Specific outcome definitions and analysis populations are not reported in the registry record.

The registry record does not report a statistical analysis plan, a sample-size justification, or interim-analysis procedures. It lists zero analyses. Although planning illustrations may be useful for thinking about future study designs, they are not evidence of observed power and do not substitute for a reported result. The study's single-group structure is essential context for interpreting every outcome: a survival description can characterize this group, but by itself it cannot separate treatment effects from other factors that influence prognosis.

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: Control cohort was derived from University of California, Los Angeles/Kaiser Permanente Los Angeles patients treated with first-line radiation therapy and temozolomide who had mostly received bevacizumab at recurrence.

Overall Study

Reasons for not completing this period:

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 Overall Survival, measured over 2 years.

Overall survival is the time from a defined starting point to death from any cause. The registry identifies overall survival as the primary endpoint and specifies the median, in months, with a 95% confidence interval. The starting point for measuring survival is not reported in the registry record, so the precise time origin cannot be confirmed from this information.

In general, the median survival time is the point at which the estimated survival curve reaches one-half. It describes the middle of the observed time-to-event distribution and is often used when follow-up times vary or some participants have not experienced the event by the end of observation. Unlike a mean, a median does not require averaging all observed times. Its interpretation depends on adequate follow-up and a clear definition of when measurement begins.

In general, a 95% confidence interval communicates uncertainty around an estimated median. A narrower interval indicates greater precision under the analysis assumptions; a wider interval indicates more uncertainty. The interval does not guarantee that a particular future study result will fall within its limits. Neither the median overall-survival estimate nor its confidence interval is reported in the registry record. Consequently, the endpoint specification is available, but the result and its precision cannot be described from this record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry record specifies a median overall-survival endpoint with a 95% confidence interval. It does not report the analysis method, the survival estimate, or the confidence interval itself. The following explanations are general descriptions of statistical concepts relevant to time-to-event outcomes, not claims about procedures used in this study.

What does a median survival estimate describe?

In general, survival analysis uses both event times and information about how long people were observed. A participant who has not had the event by the end of observation is commonly treated as censored: the analysis retains the available follow-up time without assuming that the event occurred on the last observed date. This approach allows people with different follow-up durations to contribute information. It relies on assumptions about the censoring process, including whether loss of follow-up is related to the chance of the event after accounting for relevant information. The registry record does not report censoring details or follow-up completeness for this trial.

In general, a survival curve describes the estimated probability of remaining alive over time. The median is the time at which that estimated probability reaches one-half, if it does so within the available follow-up. If the curve does not reach that point, a median may not be estimable from the observed data. No survival curve or median result is reported in the registry record, so whether the median was estimable cannot be determined.

How should a confidence interval be read?

In general, a confidence interval expresses sampling uncertainty around an estimate under a statistical procedure and its assumptions. A 95% confidence interval is not a range that contains 95% of individual survival times, nor is it a direct statement that there is a 95% probability the fixed true value lies inside the particular calculated interval. Its width is influenced by the amount and distribution of information available, including events and follow-up. Because the registry record gives no interval limits, the precision of the primary endpoint estimate cannot be assessed.

In general, estimates near the edge of a study’s follow-up can be less stable because fewer participants remain under observation at later times. The number at risk over time, the timing of events, and the handling of censoring help readers judge how much information supports a survival estimate. These details are not reported in the registry record. The listed enrollment does not by itself establish how many participants contributed to a particular endpoint analysis.

What would a hazard ratio mean?

In general, a hazard ratio compares the instantaneous event rates between groups over time, subject to the model and its assumptions. It is not a ratio of median survival times and is not automatically a measure of an absolute difference in survival. A hazard ratio requires a defined comparison. This study is listed as single group with no separate comparator, and no sponsor-reported hazard ratio is reported in the registry record. A comparative hazard-ratio interpretation is therefore not available from the record.

In general, the proportional-hazards assumption means that the relative event rate between groups is treated as constant over time. When that assumption does not hold, a single hazard ratio can conceal changes in the relative pattern over follow-up. This is a general consideration, not an assessment of this study’s data; the registry record does not report a model or diagnostics for this assumption.

How do planning illustrations differ from observed results?

In general, sample-size calculations explore how much information a future study might need under stated assumptions. They are planning tools, not measurements of the result actually observed in a completed study. The registry description of planning illustrations specifies a two-sided significance level of 0.05, equal allocation between two arms, a normal approximation, and an effect defined as a stated fraction of the observed effect. For time-to-event planning, it specifies a total number of events using the Schoenfeld approach; other planning quantities are expressed as participants per arm. These assumptions describe illustrations rather than this trial’s single-group design. Such calculations are not observed power, and the registry record does not report the trial’s own sample-size justification.

In general, planning based on a fraction of an observed effect depends on the effect estimate used as its reference. Without a reported estimate and its uncertainty, a reader cannot independently judge the basis of that reference. Nor can a planning illustration establish that a future trial will achieve its target result: actual precision and power depend on recruitment, follow-up, event occurrence, and other design and data features.

For this record, the most important methodological point is the boundary between what is specified and what is reported. The primary endpoint and its intended summary are specified, but the estimate, uncertainty limits, analysis details, and sponsor-reported hazard ratios are not reported in the registry record. General statistical concepts help explain what those items would mean; they cannot fill in absent trial results.

10. Multiplicity, Missing Data and Analysis Populations

The registry lists overall survival as the primary outcome and names several secondary outcomes: time to disease progression, progression-free survival at 6 months, radiographic response when evaluable, and median overall survival based on MGMT promoter methylation status. Testing or estimating multiple outcomes raises general questions about multiplicity. In general, the more outcomes or subgroup comparisons examined, the greater the chance that an apparently notable result could arise by chance when many hypotheses are tested. Statistical plans may address this through prespecified outcome hierarchy, adjustment procedures, or cautious interpretation. Such methods and rules are not reported in the registry record.

The record lists zero analyses. It does not report outcome-specific estimates, confidence intervals, p-values, analysis populations, or missing-data procedures. For that reason, there is no basis to describe whether secondary outcomes were formally tested, whether subgroup analyses were planned, or whether any multiplicity adjustment was used. The named MGMT promoter methylation outcome identifies a subgrouping factor, but the registry record does not report subgroup definitions, sizes, results, or an interaction analysis.

In general, missing outcome data can affect an estimate if the probability of missingness is related to the outcome or to factors associated with it. For survival outcomes, loss to follow-up and administrative end of observation are handled differently in analysis, and assumptions about censoring matter. The record does not report missingness, loss to follow-up, censoring patterns, or sensitivity analyses. It also does not describe which participants were included in each outcome analysis. The listed enrollment cannot be treated as the analysis population for every endpoint.

These omissions do not establish that a particular analysis was inappropriate; they mean its conduct and robustness cannot be assessed from the registry record. A complete interpretation would require the outcome results, methods, analysis populations, and information about follow-up and missing data.

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: altered mental status (8.6%), pulmonary embolism (5.7%), seizure (4.3%), craniotomy wound w/cerebrospinal fluid leak (2.9%), deep vein thrombosis (2.9%).

The registry lists a single group receiving bevacizumab, temozolomide, and external beam radiation. In that group, serious adverse events are recorded as affecting 54 of 70 at risk, and other adverse events as affecting 14 of 70 at risk. These are registry counts for the categories shown. They are not a randomized comparison, and they should not be read as evidence that the regimen caused every event recorded.

The listed serious adverse-event terms include altered mental status at 8.6%, pulmonary embolism at 5.7%, seizure at 4.3%, craniotomy wound with cerebrospinal fluid leak at 2.9%, deep vein thrombosis at 2.9%, and fatigue at 2.9%. These percentages are attached to the listed terms in the registry record. The record does not provide further detail about event severity grades, timing, recurrence, duration, or attribution. It also does not report deaths in the adverse-event summary.

In general, adverse-event counts and percentages depend on definitions, observation periods, and how events are coded. A participant may experience more than one event, so event-term percentages should not be added together to infer a total. Counts in a single treatment group describe recorded safety experience; without a suitable comparator, they cannot establish how much risk is attributable to treatment rather than the underlying condition, other care, or other factors. The registry record does not report a comparative safety analysis.

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

The record documents a phase II, single-group study of bevacizumab with temozolomide and external beam radiation therapy for newly diagnosed glioblastoma multiforme or gliosarcoma. It identifies overall survival as the primary endpoint and provides the intended summary as a median in months with a 95% confidence interval, using a listed timeframe of 2 years. Those design details explain the question being studied, but the median and interval are not reported in the registry record.

Because there is no separate comparison group, any reported outcome from this study would describe the experience of the enrolled group rather than provide a randomized estimate of what would have happened under another strategy. In general, outcomes in a single group can be informative for describing clinical experience, but interpretation of treatment effects is limited by the absence of a concurrent randomized comparator. Differences from external groups or historical expectations can reflect changes in patient selection, clinical practice, measurement, or follow-up, as well as treatment.

The registry lists selected serious adverse-event counts and terms. These registry entries describe recorded events but do not prove that treatment caused them. They also do not quantify relative safety compared with another strategy. The registry record does not report event attribution or comparative safety results.

The record therefore supports a limited but important reading: it specifies the study population, regimen, single-group design, and intended primary outcome, and it records selected safety information. It does not provide the primary outcome estimate, its precision, or reported analyses for the named secondary outcomes. No conclusion about the size of a treatment effect, comparative effectiveness, or comparative harm can be drawn from the registry entries alone. This is a limitation of the available record, not a claim that the study did or did not find a particular result.

13. Why This Trial Matters Statistically

This trial illustrates why design and results must be read together. The registry names an overall-survival endpoint, but an endpoint definition is not an outcome result. Without the median estimate and confidence interval, readers cannot judge either the observed survival pattern or how precisely it was estimated. Reporting uncertainty is important because a point estimate alone, even when available, can give an incomplete picture of the evidence.

The single-group design is equally central. A study can describe outcomes among patients receiving a combination, but the absence of a concurrent control group means that the observed experience is not itself a randomized comparison. This distinction prevents a descriptive outcome from being mistaken for a causal treatment effect. It also clarifies why comparative claims require evidence that addresses differences between treatment groups.

The record names several secondary outcomes and a methylation-based survival outcome, but gives no associated analyses or estimates. This highlights the importance of reporting not only which outcomes were planned, but how they were analyzed, which participants contributed data, and what uncertainty accompanied the results. In general, transparency about multiple outcomes and subgroup analyses helps readers understand how selective or exploratory findings should be interpreted.

The safety information also demonstrates the value of context. Event counts and listed percentages can describe what was recorded in the treatment group. They cannot, by themselves, distinguish treatment-related events from events connected to the disease or other care. A comparator and details about definitions and attribution would be relevant for comparative safety interpretation.

Statistically, the available record is most useful for understanding the study’s question and design, and for recognizing the limits of its posted results. It does not report the primary estimate, the analysis methods, or comparative results. Keeping those boundaries clear is necessary to avoid turning a study description into a claim about treatment effect.

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 principal limitation for statistical interpretation is that the registry record does not report the primary overall-survival estimate or its 95% confidence interval. Although the endpoint is specified as a median in months with a timeframe of 2 years, no numerical survival result is available. The registry also lists zero analyses, and it does not report sponsor-reported hazard ratios.

The study is single group, with no separate comparator. This prevents a randomized within-study comparison and limits conclusions about differences attributable to treatment. Allocation is recorded as not applicable, and masking is recorded as none. The record does not report whether any external comparison was used; such a comparison should not be assumed.

Several details needed to assess the endpoint are not reported in the registry record, including the time origin for overall survival, the analysis method, follow-up completeness, censoring information, and the number of participants contributing to each analysis. The registry does not report outcome definitions beyond their titles, analysis populations, missing-data methods, or sensitivity analyses. The listed enrollment alone cannot fill these gaps.

The registry names secondary outcomes but does not report their results or the statistical approach to multiple outcomes. It also does not report subgroup definitions or analyses for MGMT promoter methylation status. Therefore, the secondary outcomes cannot be used to assess consistency or robustness from this record.

Safety interpretation is also limited: the record lists counts and selected serious-event terms but does not report event attribution, timing, grading details, or comparative safety. The sample-size planning description is an illustration based on stated assumptions, not the trial’s own design justification or observed power. These limitations define what can be concluded from the registry record; they do not determine what may be available elsewhere.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Bevacizumab, Temozolomide, and External Beam Radiation Therapy as First-Line Therapy in Treating Patients With Newly Diagnosed Glioblastoma Multiforme or Gliosarcoma — NCT01013285.
• Registry record last updated 2020-09-21; status last verified 2016-04.
• Results first posted 2020-09-21.
• 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

The registry record describes a completed phase II, single-group study sponsored by Jonsson Comprehensive Cancer Center. It lists an enrollment of 70 and a study start of 2006-06, with primary completion in 2013-10. The study evaluated bevacizumab, temozolomide, and external beam radiation therapy as first-line treatment for newly diagnosed glioblastoma multiforme or gliosarcoma.

Overall survival is the primary endpoint, specified as a median in months with a 95% confidence interval and a timeframe of 2 years. The median and interval are not reported in the registry record. Secondary outcomes are named, but their results and analyses are not reported in the registry record. The record lists serious adverse events affecting 54 of 70 at risk and other adverse events affecting 14 of 70 at risk, along with selected serious-event terms and percentages. With no separate comparator, these results describe the study group and do not establish comparative treatment effects.