Safety and Efficacy Study of Avastin in Locally Advanced Metastatic or Recurrent Non-small Lung Cancer (NSLC) Participants: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Safety and Efficacy Study of Avastin in Locally Advanced Metastatic or Recurrent Non-small Lung Cancer (NSLC) Participants (NCT02596958), a registered phase not stated study. The primary outcome is Percentage of Participants With Adverse Drug Reactions (ADRs), Toxicities, Avastin-Related ADRs, and Serious ADRs.

2. Clinical Question

3. Trial Design

NCT02596958 is a completed non-interventional study sponsored by Hoffmann-La Roche. The registry records enrollment of 996 participants, a start date of 2007-09, and primary completion in 2013-10. The condition is non-squamous non-small cell lung cancer. The stated purpose was to collect and document routine-practice data on the safety and efficacy of intravenous bevacizumab added to platinum-based chemotherapy for first-line treatment.

The study population is described as having unresectable advanced, metastatic or recurrent disease other than predominantly squamous cell histology, with a focus on adenocarcinoma and elderly patients. The listed intervention is bevacizumab. Its arm description states that patients will receive six 3-weeks cycles with platinum-based chemotherapy, followed by maintenance bevacizumab until progression, approximately 7 months. This description identifies the intended treatment course; it does not establish that every participant completed those cycles or received maintenance for that duration.

The record lists one Bevacizumab group. Because the study is non-interventional and no allocation method is stated, it should not be read as a randomized treatment comparison. There is no documented like-for-like control group in the record. Observational results can describe what was recorded among participants, but differences between people or clinical circumstances may affect the observed outcomes.

The primary outcome concerns adverse drug reactions, toxicities, Avastin-related adverse drug reactions and serious adverse drug reactions over up to 74 months. Secondary outcomes include treatment withdrawal or modification, systemic-therapy cycles, tumor response, ECOG performance status, disease control, progression-free survival, deaths and overall survival. Numerical results for those secondary outcomes 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.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: Analysis population was defined as all participants included in the observational study, regardless of whether they finished it or not.

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: Analysis population was defined as all participants included in the observational study, regardless of whether they finished it or not. Nine hundred and ninety six (996) participants were documented but only 987 participants were included in the analysis population as 9 participants were excluded due to documented second line treatment.

6. Primary Endpoint

The registry lists the primary outcome as Percentage of Participants With Adverse Drug Reactions (ADRs), Toxicities, Avastin-Related ADRs, and Serious ADRs, measured over Up to 74 months.

The primary endpoint is the percentage of participants with adverse drug reactions, toxicities, Avastin-related adverse drug reactions and serious adverse drug reactions, assessed over up to 74 months. The registry defines an adverse drug reaction as a noxious and unintended response to a drug occurring at a normally used dose and related to its pharmacological properties. Serious adverse drug reactions are defined by outcomes such as death, a life-threatening condition, hospitalization or prolonged hospitalization, persistent or significant disability or incapacity, congenital anomaly or birth defect, or another medically important condition. Toxicity is defined by an adverse event attributed as possibly, probably or definitely related to the investigational agent. Avastin-related adverse drug reactions are described as adverse events with a possible or established relationship to Avastin.

A percentage endpoint expresses how many participants in the analysis population experienced an event, rather than how many separate event episodes occurred. This distinction matters because one participant may experience more than one event, while a participant-level percentage counts that person as affected. In general, such an endpoint is useful for describing the proportion of a treated population with recorded safety outcomes during a specified follow-up period. It does not by itself establish that the treatment caused every event, nor does it compare risk with an untreated or alternative-treatment group.

The registry reports counts for affected participants in the Bevacizumab group but does not report a full numerical result for each component of the primary endpoint, such as an interval estimate or a test of comparison. The posted information therefore supports a limited descriptive reading rather than a complete inferential assessment of the endpoint.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

What does a participant percentage describe?

For a binary outcome, each participant is classified according to whether the event was recorded during the outcome’s observation period. A participant-level percentage describes the share of the relevant group with at least one such event. It is not the same as an event rate, which would account for time at risk, and it is not necessarily the same as a count of every event episode. If one person has repeated events, a participant percentage may still count that person once for that outcome. The registry labels the primary outcome in terms of the percentage of participants and supplies affected-participant counts for the listed group.

The denominator is essential to interpreting a percentage. The safety information lists 987 participants at risk for the serious category and 987 for the other category. Enrollment is listed separately as 996. The record does not explain why these figures differ, so the at-risk denominator should not be assumed to include every enrolled participant. The record also does not give a detailed account of how event occurrence or participant follow-up was established.

What is the role of outcome definitions?

Safety terms are not interchangeable. The registry distinguishes adverse drug reactions, serious adverse drug reactions, toxicities and Avastin-related adverse drug reactions by their stated definitions. Seriousness refers to specified consequences or medical importance, while attribution concerns the assessed relationship to the investigational agent. In general, severity and seriousness are different concepts: an event can be clinically severe without meeting a regulatory seriousness criterion, or serious because of its consequences even if its intensity is not described as severe. The record’s definitions guide classification, but the registry does not report the detailed process used to apply them or whether events were reviewed by independent assessors.

The primary outcome combines several safety categories in its title. The record lists counts for serious and other affected participants, and selected serious-event terms, but does not provide a complete component-by-component numerical account of all named categories. These available figures should not be treated as interchangeable measures of the same event definition.

How should uncertainty and statistical tests be understood?

In general, an estimate from observed participants is subject to sampling and measurement uncertainty. A confidence interval expresses uncertainty around an estimate under the assumptions of the model used to calculate it. A hypothesis test evaluates data relative to a specified null hypothesis and analysis plan. Neither an interval nor a test can correct for an unsuitable comparison group, incomplete outcome ascertainment, or systematic differences between people in an observational study.

The registry record does not report confidence intervals, hypothesis tests, adjusted estimates or a statistical analysis plan for the safety or efficacy outcomes. It also does not report numerical results for the listed efficacy outcomes. Therefore, statistical significance, precision beyond the raw descriptive figures, and adjustment for potential confounding cannot be assessed from the registry record.

Over-dispersion is a general issue for count outcomes: it occurs when variation in event counts exceeds what a simple model assumes, and can make model-based uncertainty too narrow if ignored. This is relevant to event-count analyses in general, but the posted safety figures are participant counts and selected percentages, not a reported count-model analysis. The record does not state whether any over-dispersion assessment or model-based analysis was performed.

What does the planning illustration mean?

Any planning illustration associated with the posted results is distinct from the study’s design and observed results. The stated illustration uses a two-sided significance level of 0.05, equal allocation between two arms and a normal approximation, with an effect to detect expressed as a fraction of the observed effect. For time-to-event outcomes it gives a total number of events; for other outcomes it gives participants per arm. Such values are hypothetical planning quantities, not observed participant outcomes and not observed power. They do not show that the study was designed with those assumptions.

This distinction is particularly important because the registry describes a non-interventional study and does not document a randomized, two-arm control comparison. A two-arm planning exercise is not evidence that the study enrolled or analyzed two comparable arms. The record does not report a sample-size justification for the observational study, and an illustration based on an observed effect cannot substitute for one.

How should the observational design shape interpretation?

In general, observational studies document care as it occurs rather than assigning treatment by randomization. This can make the record informative about treatment use and recorded outcomes in the study population, but it also leaves room for confounding. Factors associated with both treatment and outcome can influence observed patterns. Without a suitable comparison group, adjustment strategy and transparent analysis details, descriptive event counts should not be interpreted as causal treatment effects.

The registry says allocation is not stated and identifies no like-for-like control comparison. It does not report a confounding-adjustment method, missing-data method, or detailed analytic population for each individual outcome. These omissions limit what can be inferred beyond the reported descriptive safety counts.

10. Multiplicity, Missing Data and Analysis Populations

The registry lists a primary safety outcome and secondary outcomes covering treatment withdrawal or modification, systemic-therapy cycles, best tumor response, ECOG performance status, disease control, progression-free survival, deaths and overall survival. Because several outcomes are considered, multiplicity is a general statistical concern: examining multiple outcomes can increase the chance of at least one apparently notable result when many tests are conducted. The registry record does not report a multiplicity adjustment, hierarchy among secondary outcomes, or a plan for interpreting multiple tests. It also reports no statistical analyses for these outcomes.

Missing-data handling is not reported in the registry record. In general, incomplete follow-up or missing outcome assessments can affect both the estimated proportion of participants with an event and the interpretation of time-to-event outcomes. The record does not describe how participants with incomplete data were handled, whether any imputation was used, or how censoring was defined for progression-free or overall survival. No particular method should therefore be assumed.

The primary outcome description defines the analysis population as all participants included in the observational study, regardless of whether they finished it. That statement describes inclusion in the population, but it does not explain how missing outcome information for those participants was treated. Enrollment is 996; the safety group lists 987 at risk. The registry record does not explain the difference between these figures.

These omissions matter because a stated analysis population does not by itself guarantee complete outcome data, and inclusion regardless of study completion does not specify how incomplete records contribute to an estimate. The posted safety counts can be read descriptively using their listed denominators, but the record does not provide enough information to evaluate missingness patterns or their possible influence on the reported figures.

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: pulmonary embolism (1.5%), hypertension (1.5%), pneumonia (0.9%), haemoptysis (0.7%), dyspnoea (0.5%).

The Bevacizumab group lists 987 participants at risk for the serious adverse-reaction category, with 110 affected, and 987 at risk for the other category, with 851 affected. These are participant counts, not counts of every event episode. The record also identifies Pulmonary embolism and Hypertension at 1.5% each among the listed serious-event terms, followed by Pneumonia at 0.9%, Haemoptysis at 0.7%, and Dyspnoea and Leukopenia at 0.5% each.

Interpret these figures within the definitions and follow-up in the registry. Serious adverse drug reactions are classified by specified consequences or medical importance; the term does not simply mean an event was intense. The primary outcome’s follow-up period is up to 74 months, but the record does not report individual follow-up duration or event timing for these safety counts. A selected list of serious-event terms does not establish that no other serious events occurred.

The registry does not report a death count for this safety group, nor does it provide confidence intervals or a comparison group. The counts therefore describe the recorded group and do not quantify a comparative treatment effect or establish causation.

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

The record documents a non-interventional study of intravenous bevacizumab added to platinum-based chemotherapy for first-line treatment of locally advanced, metastatic or recurrent non-small cell lung cancer other than predominantly squamous cell histology. It describes a focus on adenocarcinoma and elderly patients in daily routine, and reports enrollment of 996. The safety information gives affected-participant counts for the Bevacizumab group and percentages for selected serious-event terms.

Those descriptive data show what the registry records for that group; they do not establish that bevacizumab caused every reported event. The study has no documented like-for-like control comparison, and allocation is not stated. Without such a comparison and detailed analysis information, the record cannot establish whether the treatment changes safety outcomes relative to another approach. The figures also do not describe how risk varies across individual participants or over time.

The registry lists efficacy outcomes, including tumor response, disease control, progression-free survival and overall survival, but their numerical results are not reported in the registry record. The safety counts cannot be used to infer those efficacy outcomes. Nor does the record provide confidence intervals or statistical tests that would show the precision of the reported estimates.

In general, a treatment effect requires a defined comparison and an analysis that addresses uncertainty and, for observational data, potential differences between groups. The posted record is useful as a description of the study’s purpose, population, planned treatment and selected recorded safety information. It does not establish comparative efficacy, a causal safety effect, or the completeness of event ascertainment. These distinctions keep the interpretation aligned with what the registry actually reports.

13. Why This Trial Matters Statistically

Statistically, this record is a useful example of the difference between describing outcomes and estimating a comparative treatment effect. It documents an observational study of bevacizumab with platinum-based chemotherapy and reports selected participant-level safety information. Those data can characterize recorded events in the study group, but without a like-for-like control comparison they cannot identify how outcomes would have differed under another treatment strategy.

The record also illustrates why endpoint definitions and denominators should be read together. Seriousness, attribution and toxicity are defined separately, while the safety information reports participants at risk and affected participants. Enrollment and the safety denominator are not the same registry figures, and the record does not explain the difference. That makes it important to use the stated denominator for the reported safety count rather than treating enrollment as the denominator for every outcome.

Another statistical lesson is that a list of outcomes is not equivalent to a report of their analyses. The registry names multiple efficacy outcomes but provides no numerical results for them. It also does not report confidence intervals, hypothesis tests, missing-data methods, or multiplicity handling. Without these details, readers cannot evaluate precision, the treatment of incomplete follow-up, or how multiple outcomes were interpreted.

Finally, a planning illustration based on an observed effect is conceptually separate from a study’s original design. Its assumptions do not document the rationale used to enroll participants, and a hypothetical two-arm calculation does not create a control comparison in a non-interventional study. Keeping these distinctions clear prevents descriptive registry data and planning quantities from being mistaken for causal or confirmatory 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 registry record has important limitations for interpreting this trial’s results. It describes a non-interventional study and does not document a randomized comparison or a like-for-like control group. Allocation is not stated. As a result, the listed safety counts are descriptive and cannot isolate the effect of bevacizumab from other influences.

Although enrollment is 996, the safety group lists 987 participants at risk. The registry does not explain this difference. It also does not provide participant-level follow-up, event timing, detailed event ascertainment, or the number of deaths for the safety group. The serious-event terms are selected entries, not an explicitly complete account of all safety outcomes.

The primary outcome includes several defined safety categories, but the record does not present numerical results for every component or provide confidence intervals and statistical tests. It lists multiple secondary outcomes, while numerical efficacy results are not reported in the registry record. The statistical analysis plan, confounding-adjustment approach, multiplicity handling and missing-data methods are also not reported.

The arm description specifies six 3-weeks cycles of bevacizumab with platinum-based chemotherapy followed by maintenance until progression, approximately 7 months. It does not give participant-level treatment duration or establish that every participant followed this course. The record’s analysis population includes participants whether or not they finished the study, but it does not explain how missing outcome information was handled.

These limitations restrict interpretation to the information recorded: study characteristics and selected descriptive safety figures. They prevent a reliable assessment of comparative efficacy, causal safety effects, or the precision and completeness of the outcome estimates.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Safety and Efficacy Study of Avastin in Locally Advanced Metastatic or Recurrent Non-small Lung Cancer (NSLC) Participants — NCT02596958.
• Registry record last updated 2016-04-04; status last verified 2016-03.
• Results first posted 2016-03-04.
• 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

NCT02596958 is a completed, non-interventional study sponsored by Hoffmann-La Roche. The registry lists enrollment of 996, a start date of 2007-09 and primary completion in 2013-10. It concerns non-squamous non-small cell lung cancer and the first-line use of intravenous bevacizumab with platinum-based chemotherapy, with a focus on adenocarcinoma and elderly patients in daily routine.

The primary outcome concerns adverse drug reactions, toxicities, Avastin-related adverse drug reactions and serious adverse drug reactions over up to 74 months. The Bevacizumab group lists 987 participants at risk and 110 affected in the serious category, as well as 851 affected in the other category. Selected serious-event terms and percentages are also recorded.

The registry lists several secondary efficacy outcomes, but their numerical results are not reported in the registry record. No like-for-like control comparison, statistical analysis results, missing-data methods or multiplicity approach are reported. The safety counts should therefore be read as descriptive information for the listed observational group, not as estimates of a comparative treatment effect.