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 Study of Atezolizumab and Bevacizumab With Y-90 TARE in Patients With Unresectable Hepatocellular Carcinoma (HCC) (NCT04541173), a randomized phase 2 study. The primary outcome is Progression Free Survival (PFS) by RECIST 1.1.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT04541173 |
| Phase | Phase 2 |
| Condition | Hepatocellular Carcinoma |
| Allocation | Randomized |
| Design model | Parallel |
| Masking | None (open label) |
| Enrollment | 6 |
| Arms in the primary outcome | n/a |
| Lead sponsor | Aiwu Ruth He, MD |
| Results posted | Yes |
2. Clinical Question
Population
Participants with unresectable hepatocellular carcinoma (HCC) were eligible for this study. The registry describes the disease as unresectable advanced-stage HCC. A more detailed description of eligibility criteria or the characteristics of the enrolled participants is not reported in the registry record.
Intervention
Arm B received Y-90 transarterial radioembolization (TARE), followed by bevacizumab and atezolizumab. The registry describes this sequence as TARE followed by the two medicines; further details about treatment timing, dose, or duration are not reported in the registry record.
Comparator
Arm A received Y-90 TARE alone. The trial was randomized, open-label, and parallel-group. The allocation ratio and any procedures used to conceal the allocation sequence are not reported in the registry record.
Primary question
The primary question concerned progression-free survival (PFS) by RECIST 1.1, defined as the time from registration until disease progression or death from any cause. The planned PFS analyses were not conducted following early termination. The registry instead presents raw RECIST 1.1 response data by arm, without a reported inferential comparison of PFS.
3. Trial Design
This was a randomized, open-label, parallel-group phase II study in people with unresectable HCC. Its stated comparison was Y-90 TARE followed by bevacizumab and atezolizumab versus Y-90 TARE alone. Arm A was TARE alone; Arm B was TARE followed by bevacizumab and atezolizumab. Because masking was none, the study was open-label.
The registry records enrollment of 6 participants. It lists the study start as 2020-11-30 and primary completion as 2023-06-18, and gives the study status as terminated. The registry attributes early termination to the funder and sponsor-investigator. It does not report the reason for that decision beyond this attribution.
The primary endpoint was PFS by RECIST 1.1, with a stated observation timeframe of up to a maximum of 16 months. The registry explains that, because of early termination, pre-planned analyses were not conducted. Instead, raw response data by arm are presented. A number of planned secondary outcome topics are listed, including adverse events, PFS and time to progression by mRECIST, response rates by mRECIST and RECIST 1.1, overall survival, and subject function. The presence of an outcome in that list does not establish that a complete analysis or comparative result was reported.
Details such as the intended allocation ratio, eligibility rules, treatment schedules, study sites, and the planned statistical analysis procedures are not reported in the registry record. Those omissions limit how fully the design and conduct can be evaluated.
4. Participant Flow and Accounting
The registry reports how participants moved through each stage of the study. All counts below are exactly as posted; missing counts are not inferred from other stages.
Overall Study
| Stage | Arm A: TARE Alone | Arm B: TARE Then Bevacizumab and Atezolizumab |
|---|---|---|
| STARTED | 3 | 3 |
| COMPLETED | 3 | 3 |
| NOT COMPLETED | 0 | 0 |
Analysis population for the primary outcome, as defined in the registry: Due to the early termination of the study by the funder and sponsor-investigator, pre-planned analyses were not conducted. In lieu of this analysis, the raw response data per RECIST 1.1 is presented per-arm.
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 | Arm A | Arm B | Total |
|---|---|---|---|---|
| Participants analysed | 3 | 3 | 6 | |
| Age, Continuous | years | 72 (59 to 82) | 72 (67 to 75) | 72 (59 to 82) |
| Sex: Female, Male: Female | Participants | 2 | 1 | 3 |
| Sex: Female, Male: Male | Participants | 1 | 2 | 3 |
| Ethnicity (NIH/OMB): Hispanic or Latino | Participants | 1 | 0 | 1 |
| Ethnicity (NIH/OMB): Not Hispanic or Latino | Participants | 2 | 3 | 5 |
| Ethnicity (NIH/OMB): Unknown or Not Reported | Participants | 0 | 0 | 0 |
| Race (NIH/OMB): American Indian or Alaska Native | Participants | 0 | 0 | 0 |
| Race (NIH/OMB): Asian | Participants | 0 | 0 | 0 |
| Race (NIH/OMB): Native Hawaiian or Other Pacific Islander | Participants | 0 | 0 | 0 |
| Race (NIH/OMB): Black or African American | Participants | 1 | 1 | 2 |
| Race (NIH/OMB): White | Participants | 2 | 2 | 4 |
| Race (NIH/OMB): More than one race | Participants | 0 | 0 | 0 |
| Race (NIH/OMB): Unknown or Not Reported | Participants | 0 | 0 | 0 |
| Region of Enrollment: United States | participants | 3 | 3 | 6 |
| ECOG Performance Status: ECOG = 0 | Participants | 1 | 1 | 2 |
| ECOG Performance Status: ECOG = 1 | Participants | 2 | 2 | 4 |
6. Primary Endpoint
The registry lists the primary outcome as Progression Free Survival (PFS) by RECIST 1.1, measured over Up to a maximum of 16 months..
| Element | Registry entry |
|---|---|
| Result type | Count Of Participants |
| Measure of spread | not applicable |
| Unit | Participants |
| Endpoint classification | Binary Endpoint |
PFS is a time-to-event endpoint. In this study, it was defined as the time from registration until disease progression according to RECIST 1.1 or death from any cause. It therefore combines progression and death into one endpoint: either event can mark the end of a participant’s PFS time. The stated timeframe was up to a maximum of 16 months.
RECIST 1.1 provides criteria for classifying tumor response. The registry description identifies complete response as disappearance of all target lesions, partial response as a decrease of at least 30% in the sum of the longest diameters of target lesions, progressive disease as an increase of at least 20% in tumor burden relative to nadir or the appearance of one or more new lesions, and stable disease as not meeting the criteria for complete response, partial response, or progressive disease.
As a general statistical point, PFS can represent both tumor progression and death within a single endpoint, and it can capture when an event occurs rather than only whether one occurs. However, evaluating a time-to-event endpoint requires usable event and follow-up information, along with an analysis appropriate to those data. The registry says the planned PFS analyses were not conducted after early termination. It presents raw response data per arm instead, so the record does not report a completed comparative PFS analysis or a corresponding estimate of its precision.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The registry describes a randomized comparison, but its primary endpoint result cannot be interpreted as a completed test of the study question. Although PFS by RECIST 1.1 was designated as primary, the registry explicitly states that early termination meant the pre-planned analyses were not conducted. Raw response data per arm are presented in lieu of that analysis. No inferential PFS comparison, effect estimate, confidence interval, or P-value is reported in the registry record.
The enrollment was 6 participants. With so few participants, any arm-level counts are necessarily based on very limited information. A small count can change substantially with the experience of a single participant, and differences in the observed counts do not by themselves establish a reliable treatment contrast. Randomization describes how treatment assignment was intended to occur; it does not remove the uncertainty that results from limited enrollment or replace an analysis of the primary endpoint.
The registry lists several secondary outcome topics, including response and time-to-progression measures using mRECIST and RECIST 1.1, overall survival, subject function, and adverse events. The number of listed outcome measures is 9, but the number of analyses is 0. These entries should not be read as a set of completed comparative findings. For any outcome without a reported result, the result is not reported in the registry record.
The adverse-event counts are descriptive. They show the numbers of participants recorded with serious and other adverse events in each arm, as well as deaths. They do not provide a basis for a precise comparative estimate, and the small numbers make such comparisons particularly uncertain. The listed serious adverse-event term is dyspnea, with a reported value of 33.3%; the registry entry does not establish an arm-specific estimate for that term.
Any sample-size calculations used for planning illustration should be understood as hypothetical planning quantities, not as trial findings or observed power. The registry’s analysis shortfall is central to interpretation: the posted information describes the intended endpoint and gives limited response and safety data, but does not supply a completed PFS comparison. It therefore cannot establish the magnitude or precision of a treatment effect on the primary endpoint.
9. Statistical Methods Explained
What does randomization contribute?
In general, randomization assigns participants to study groups using a chance-based process. It is intended to make the groups comparable, on average, with respect to factors that could affect outcomes, including factors that are not measured. It does not guarantee that two groups will be balanced in a particular small trial. The registry identifies this study as randomized but does not report the allocation ratio, sequence-generation method, or allocation-concealment procedures. The assigned groups contained 3 participants each in the adverse-event record.
Open-label describes a study in which treatment assignment is not masked from participants or study personnel. That is the masking status recorded for this trial. Awareness of treatment can sometimes influence care, reporting, or assessment; whether and how such influences were addressed is not reported in the registry record. This is a general consideration, not evidence that any particular bias occurred in this study.
How should the primary endpoint be analyzed?
In general, PFS is analyzed as a time-to-event outcome because participants may have different lengths of follow-up and may not all experience progression or death during the observation period. Such analyses use both event information and follow-up time. A confidence interval, when reported, expresses the uncertainty around an estimated quantity under the statistical method used. It does not make an imprecise estimate precise, and it is not a guarantee that the true value lies within a particular range.
The registry defines PFS as time from registration to RECIST 1.1 progression or death from any cause, with follow-up stated as up to a maximum of 16 months. It also says the planned analyses were not conducted after early termination. Accordingly, no time-to-event estimate, confidence interval, or hypothesis test for PFS is reported in the registry record. Raw response data are not interchangeable with a completed PFS analysis: response classifications do not, by themselves, provide the times to progression or death needed to estimate the time-to-event contrast.
What do the response criteria describe?
RECIST 1.1 is a framework for classifying tumor response from lesion measurements and the appearance of new lesions. In the registry description, complete response means disappearance of all target lesions; partial response requires at least a 30% decrease in the sum of the longest diameters of target lesions; progressive disease includes an increase of at least 20% in tumor burden relative to nadir or a new lesion; and stable disease is the category for cases that do not meet the other stated criteria. These are classification rules. They do not alone indicate how long a response lasts or whether a difference between arms is statistically distinguishable from chance.
The registry also names mRECIST outcomes among secondary outcomes. The full analysis procedures for those outcomes are not reported in the registry record. No extra assumptions about how the measures were applied should be made.
What can counts and planning calculations tell us?
Adverse-event figures are participant counts: they indicate how many participants in a group were recorded as having an event in the stated category. Counts are useful descriptions, particularly when the number of participants is small, but they do not adjust for follow-up duration, differences in exposure, or other characteristics. The registry does not report those details in the adverse-event entry.
General statistical planning calculations can illustrate how many participants might be needed under specified assumptions about the target effect, significance level, allocation, and analysis method. Such calculations are design illustrations, not observed outcomes and not observed power. The registry describes a planning framework using a two-sided significance level of 0.05, equal allocation, and a normal approximation, with the target effect expressed as a fraction of the observed effect. It further distinguishes total events for time-to-event illustrations from participants per arm for other outcomes. These assumptions do not establish that the trial itself was designed with those settings. The original sample-size justification is not reported in the registry record.
In this trial, the early termination and absence of the pre-planned PFS analysis are more important than a hypothetical planning calculation when judging the available evidence. A planning illustration cannot recreate missing outcome analyses or supply an estimate and uncertainty interval that the registry does not report.
10. Multiplicity, Missing Data and Analysis Populations
Multiplicity arises when a study evaluates multiple outcomes, time points, or comparisons. In general, conducting many statistical tests can increase the chance of obtaining an apparently notable result by chance unless the analysis plan addresses that issue. The registry lists 9 outcome measures, including several response and time-to-progression outcomes using different criteria, as well as survival, function, and adverse events. The registry record does not report a multiplicity adjustment or a hierarchy of confirmatory tests. It is therefore not possible to determine from the record how any multiplicity was planned to be handled.
The primary PFS analysis was not conducted after early termination. The record does not report an analysis of missing outcome data, the amount or pattern of missingness, censoring details, or sensitivity analyses. These should not be inferred from the statement that raw response data are presented per arm.
The analysis populations are also not described in sufficient detail to identify whether participants were analyzed according to randomized assignment, treatment received, or another rule. The registry does not report a formal intention-to-treat definition or other analysis-population definitions. The count of 6 enrolled participants should not be treated as proof that all were included in every endpoint analysis.
In general, incomplete follow-up and missing measurements can affect estimates, and the appropriate response depends on why data are missing and on the planned analysis. Here, the registry does not report enough detail to assess those issues for the primary endpoint. That uncertainty adds to the limits imposed by the uncompleted PFS analysis and the small enrollment.
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 |
|---|---|---|---|
| Arm A | 1 | 3 | 33.3% |
| Arm B | 0 | 3 | 0.0% |
Deaths
| Arm | Deaths (participants affected of at risk) |
|---|---|
| Arm A | 0 of 3 |
| Arm B | 0 of 3 |
Other (non-serious) adverse events
Participants with at least one non-serious event at or above the registry's 0% reporting threshold.
| Arm | Participants affected of at risk |
|---|---|
| Arm A | 2 of 3 |
| Arm B | 3 of 3 |
Most frequent serious adverse event terms
| Event term | Organ system | Arm A | Arm B |
|---|---|---|---|
| DYSPNEA | Respiratory, thoracic and mediastinal disorders | 1 of 3 | 0 of 3 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Arm A | Arm B |
|---|---|---|---|
| FATIGUE | General disorders | 2 of 3 | 3 of 3 |
| NAUSEA | Gastrointestinal disorders | 1 of 3 | 1 of 3 |
| HYPERTENSION | Vascular disorders | 0 of 3 | 2 of 3 |
| PLATELET COUNT DECREASED | Investigations | 1 of 3 | 0 of 3 |
| ABDOMINAL DISTENSION | Gastrointestinal disorders | 0 of 3 | 1 of 3 |
| ARTHRALGIA | Musculoskeletal and connective tissue disorders | 0 of 3 | 1 of 3 |
| BONE PAIN | Musculoskeletal and connective tissue disorders | 0 of 3 | 1 of 3 |
| CHILLS | General disorders | 0 of 3 | 1 of 3 |
| DYSGEUSIA | Nervous system disorders | 0 of 3 | 1 of 3 |
| DYSPEPSIA | Gastrointestinal disorders | 0 of 3 | 1 of 3 |
Serious events with the highest arm-level rate: dyspnea (33.3%).
The adverse-event record gives participant counts by arm. In Arm A, 1 of 3 participants was recorded with a serious adverse event, and 2 of 3 were recorded with other adverse events. In Arm B, 0 of 3 participants were recorded with a serious adverse event, and 3 of 3 were recorded with other adverse events. The recorded number of deaths was 0 in each arm.
These are descriptive counts, not estimates of comparative risk. With 3 participants per arm, each participant represents a substantial part of the group, so the counts provide very limited precision. The registry lists dyspnea as the top serious adverse-event term, with a reported value of 33.3%. The entry does not provide an arm-specific value for that term, so it should not be assigned to either arm on the basis of this record.
As a general point, adverse-event counts depend on how events were defined, collected, and attributed, and on the period during which participants were observed. The registry entry does not provide enough detail to assess those aspects or to compare exposure time between arms. The figures therefore describe what was recorded, rather than establishing a difference in safety between the treatment groups.
12. What the Result Does, and Does Not, Mean
The posted results establish that this was a randomized, open-label phase II study comparing TARE alone with TARE followed by bevacizumab and atezolizumab in unresectable HCC. The registry records 6 enrolled participants and reports that the study was terminated early. It also states that the planned analyses were not conducted and that raw RECIST 1.1 response data by arm were presented instead.
Those details do not amount to a completed answer about the primary endpoint. PFS was defined as time from registration until RECIST 1.1 progression or death from any cause, but the registry does not report a comparative PFS estimate, its uncertainty, or a statistical test. Without those results, the direction and precision of a PFS contrast cannot be established from the registry record. The study’s stated primary question therefore remains unresolved in the posted analysis.
The adverse-event entries describe small counts in each arm. They can be read as a record of reported events, but they cannot support a precise comparison between groups. The registry’s listed secondary outcomes likewise should not be treated as completed analyses merely because they appear in the outcome list.
This interpretation is not a conclusion that either treatment is beneficial, ineffective, safer, or less safe. Rather, the available record is limited: early termination prevented the pre-planned primary analysis, and the enrolled group was small. Any planning illustrations are not substitutes for observed results or evidence of observed power. They describe calculations under assumptions, while the study findings are the recorded participant data and analyses. The record does not support a definitive comparative conclusion about PFS.
13. Why This Trial Matters Statistically
This trial illustrates why the analysis plan and the status of outcome reporting matter as much as the endpoint named in a protocol or registry entry. PFS is identified as the primary outcome, but the registry states that its planned analyses were not conducted after early termination. A primary endpoint designation alone does not create an estimate of treatment effect; interpretation requires the relevant outcome data and an analysis that addresses follow-up and event timing.
The study also shows the distinction between an outcome’s planned definition and a reported result. RECIST 1.1 criteria describe how response categories are classified, while PFS additionally requires the timing of progression or death. Raw response information may be informative descriptively, but it does not replace the planned time-to-event analysis.
Enrollment of 6 participants also makes the limits of descriptive counts apparent. The adverse-event counts provide a straightforward account of recorded participants, but they are too limited to support precise comparisons. In general, uncertainty should be made visible rather than obscured by an apparent difference between small counts. The registry does not report a completed inferential analysis that would quantify uncertainty for the primary comparison.
Finally, the listed secondary outcomes and planning framework should be distinguished from completed trial findings. Outcome listings do not demonstrate that analyses were performed, and sample-size planning illustrations are not observed power. These distinctions help readers separate the intended design, the data that were recorded, and the conclusions that the reported analyses can support.
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 consequential limitation is that the study was terminated and the pre-planned analyses were not conducted. The registry presents raw RECIST 1.1 response data by arm in place of the planned primary analysis, but a comparative PFS estimate and its precision are not reported. This prevents assessment of the primary endpoint as a time-to-event comparison.
Enrollment was 6 participants, which sharply limits the information available for both efficacy and safety interpretation. The adverse-event counts are small descriptive totals, not precise comparative estimates. The registry does not report the arm-specific serious-event term for dyspnea, so the listed value of 33.3% cannot be allocated to a treatment group from this record.
Several design and analysis details are not reported in the registry record, including the allocation ratio, detailed eligibility criteria, the original sample-size justification, analysis-population definitions, missing-data procedures, censoring details, and a multiplicity strategy. The record also does not give enough information to assess the completeness of follow-up or the conduct of outcome assessments.
The outcome list includes several secondary measures, but the record reports 0 analyses. The presence of an outcome label should not be taken to mean that a result was analyzed or reported. Together, the early termination, small enrollment, and limited analysis detail leave substantial uncertainty about the comparative outcomes and the scope of any conclusions.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Study of Atezolizumab and Bevacizumab With Y-90 TARE in Patients With Unresectable Hepatocellular Carcinoma (HCC) — NCT04541173.
- Registry record last updated 2024-06-05; status last verified 2024-06.
- Results first posted 2024-06-05.
- 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
The registry describes a randomized, open-label, parallel-group phase II study in unresectable HCC. It compared Y-90 TARE alone with Y-90 TARE followed by bevacizumab and atezolizumab. Enrollment was 6, and the study status is terminated.
The primary endpoint was PFS by RECIST 1.1, defined as time from registration until progression or death from any cause, with a stated timeframe of up to a maximum of 16 months. The registry attributes the early termination to the funder and sponsor-investigator and says the pre-planned analyses were not conducted. Raw RECIST 1.1 response data are presented per arm in lieu of the planned analysis.
The adverse-event entry records serious events in 1 participant in Arm A and 0 in Arm B, other events in 2 participants in Arm A and 3 in Arm B, and 0 deaths in each arm. The registry lists 9 outcome measures and 0 analyses. A completed comparative PFS result is not reported in the registry record.