Avelumab in Previously Untreated Patients With Epithelial Ovarian Cancer (JAVELIN OVARIAN 100): Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Avelumab in Previously Untreated Patients With Epithelial Ovarian Cancer (JAVELIN OVARIAN 100) (NCT02718417), a randomized phase 3 study. The primary outcome is Progression-Free Survival (PFS) as Assessed by Blinded Independent Central Review (BICR).

2. Clinical Question

The trial was designed to evaluate efficacy and safety in previously untreated epithelial ovarian cancer and related cancers. The two avelumab strategies differ in when avelumab was added: one used it after chemotherapy, while the other started it alongside chemotherapy and continued it afterward. These are distinct treatment strategies, and the record reports each comparison against the same observation group.

The primary endpoint focused on the time until disease progression or death. The registry also lists overall survival, investigator-assessed progression-free survival, objective response, duration of response, and maintenance progression-free survival among its secondary outcomes. Those outcomes provide complementary information, but the central question is whether the randomized groups differed in the timing of progression or death under the primary endpoint definition.

3. Trial Design

This was a randomized, open-label, multicenter, Phase 3 study with a parallel-group design and no masking. The registry lists 998 participants enrolled and three groups: chemotherapy followed by observation, chemotherapy followed by avelumab maintenance, and chemotherapy combined with avelumab followed by avelumab maintenance. The primary description identifies the full analysis set as all randomized participants.

The primary endpoint was progression-free survival assessed by blinded independent central review. The registry describes a maximum duration of 27 months for the primary timeframe. The trial status is terminated. Its primary purpose was to compare the two avelumab strategies with platinum-based chemotherapy followed by observation in newly diagnosed patients.

Open-label means participants and study personnel were not masked to assigned treatment. However, the primary endpoint was assessed by a blinded independent central review, a design feature intended to keep that endpoint assessment separate from knowledge of treatment assignment. The registry describes an international, multicenter study in its brief summary, but the number and locations of participating centers are not reported in the registry record.

The three group sizes in the primary results were 332 for chemotherapy followed by avelumab, 331 for chemotherapy plus avelumab followed by avelumab, and 335 for chemotherapy followed by observation. These are the group counts reported for that endpoint, rather than an explanation of how participants were allocated over time. The registry record does not report the original sample-size justification, the details of randomization, or whether interim analyses were planned or conducted.

The study lists six analyses and 36 outcome measures. The registry record does not report a complete statistical analysis plan or explain the full relationship between the number of listed analyses and outcome measures. As a result, interpretation of individual outcomes should follow the definitions and results actually posted rather than assumptions about the trial's planned hierarchy.

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.

Chemotherapy Phase (CP)

Reasons for not completing this period:

Maintenance Phase (MP)

Reasons for not completing this period:

Observation Phase (OP)

Reasons for not completing this period:

Follow-up Phase

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: The full analysis set included all randomized participants.

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: The full analysis set included all randomized participants.

6. Primary Endpoint

The registry lists the primary outcome as Progression-Free Survival (PFS) as Assessed by Blinded Independent Central Review (BICR), measured over Baseline to progression of disease or discontinuation from the study or death, whichever occurred first (maximum duration of 27 months).

The primary endpoint was progression-free survival assessed by blinded independent central review. It measures the time from randomization until disease progression or death. Participants without a recorded event could be censored at their last adequate tumor assessment under the registry's stated rules; the description also specifies censoring in certain circumstances involving new anti-cancer therapy or multiple missed assessments.

Progression was defined using RECIST version 1.1. The record describes progression as an increase of at least 20% in the sum of target-lesion diameters from the smallest sum on study, together with an absolute increase of at least 5 millimeters, or the appearance of one or more new lesions. The registry states that the analysis used the Kaplan-Meier method.

Time-to-event endpoints are useful when the timing of progression or death matters and participants may have different lengths of follow-up. They can incorporate information from participants who have not yet had an event through censoring, rather than treating their follow-up as if the event had occurred. This approach depends on appropriate endpoint ascertainment and censoring assumptions; the registry description gives the censoring rules but does not report diagnostics or additional sensitivity analyses.

The median is a summary of the event-time distribution, while a hazard ratio compares event rates over follow-up under a proportional-hazards interpretation. These summaries answer related but different questions. The registry's primary comparisons are reported as hazard ratios; the primary group results also include median estimates for the two avelumab groups, while the observation group's median estimate is not reported in the registry record.

7. Results Posted in the Registry

• Chemotherapy Followed by Avelumab vs Chemotherapy Followed by Observation: hazard ratio 1.43 (95% CI 1.05–1.95), reported p = 0.989 (as reported in the registry).
• Chemotherapy + Avelumab Followed by Avelumab vs Chemotherapy Followed by Observation: hazard ratio 1.14 (95% CI 0.83–1.56), reported p = 0.793 (as reported in the registry).

8. Secondary Efficacy Endpoints

The registry also posts results for secondary outcomes. For each outcome below, the endpoint type, the test applied to the posted summary statistics, the result and its interpretation are given in turn. Secondary endpoints are usually not adjusted for multiple testing, so they support rather than confirm the primary finding.

Overall Survival

• Endpoint type: Time to event: compared as a hazard ratio.
• Test: Hazard ratio as reported by the sponsor (Log Rank); it was not recalculated.
• Result:
  • Chemotherapy Followed by Avelumab vs Chemotherapy Followed by Observation: hazard ratio 1.53 (95% CI 0.76–3.08), reported p = 0.885 (as reported in the registry).
  • Chemotherapy + Avelumab Followed by Avelumab vs Chemotherapy Followed by Observation: hazard ratio 1.55 (95% CI 0.78–3.11), reported p = 0.895 (as reported in the registry).
• Interpretation:
  • The 95% confidence interval includes no difference (a ratio of 1), so these data do not show a statistically significant difference between Chemotherapy Followed by Avelumab vs Chemotherapy Followed by Observation and the control. The interval gives the range of effects that remain compatible with the data.
  • The 95% confidence interval includes no difference (a ratio of 1), so these data do not show a statistically significant difference between Chemotherapy + Avelumab Followed by Avelumab vs Chemotherapy Followed by Observation and the control. The interval gives the range of effects that remain compatible with the data.

Progression-Free Survival (PFS) as Assessed by Investigator

• Endpoint type: Time to event: compared as a hazard ratio.
• Test: Hazard ratio as reported by the sponsor (Log Rank); it was not recalculated.
• Result:
  • Chemotherapy Followed by Avelumab vs Chemotherapy Followed by Observation: hazard ratio 1.21 (95% CI 0.94–1.58), reported p = 0.928 (as reported in the registry).
  • Chemotherapy + Avelumab Followed by Avelumab vs Chemotherapy Followed by Observation: hazard ratio 0.90 (95% CI 0.69–1.19), reported p = 0.237 (as reported in the registry).
• Interpretation:
  • The 95% confidence interval includes no difference (a ratio of 1), so these data do not show a statistically significant difference between Chemotherapy Followed by Avelumab vs Chemotherapy Followed by Observation and the control. The interval gives the range of effects that remain compatible with the data.
  • The 95% confidence interval includes no difference (a ratio of 1), so these data do not show a statistically significant difference between Chemotherapy + Avelumab Followed by Avelumab vs Chemotherapy Followed by Observation and the control. The interval gives the range of effects that remain compatible with the data.

Percentage of Participants With Objective Response as Assessed by Investigator

• Endpoint type: Binary: the percentage of participants with the event (counts rebuilt from the posted percentages and group sizes).
• Test: Unadjusted two-proportion z-test, with a Wald 95% confidence interval for the risk difference.
• Result:
  • Chemotherapy Followed by Avelumab: 25.9% (86/332) versus 27.8% (93/335) on control; risk difference -1.9 percentage points (95% CI -8.6 to 4.9), risk ratio 0.93 (0.73–1.20); unadjusted two-proportion z-test p = 0.588.
  • Chemotherapy + Avelumab Followed by Avelumab: 31.1% (103/331) versus 27.8% (93/335) on control; risk difference 3.4 percentage points (95% CI -3.6 to 10.3), risk ratio 1.12 (0.89–1.42); unadjusted two-proportion z-test p = 0.342.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between Chemotherapy Followed by Avelumab and the control. The interval gives the range of effects that remain compatible with the data.
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between Chemotherapy + Avelumab Followed by Avelumab and the control. The interval gives the range of effects that remain compatible with the data.

The secondary outcomes address several related but distinct questions: overall survival, investigator-assessed progression-free survival, objective response, response duration, and maintenance progression-free survival. The posted results do not include numerical estimates for every listed secondary outcome. In particular, overall-survival medians are not reported in the registry record, while some time-to-event comparisons and investigator-assessed response results are posted.

Across the available secondary comparisons, the uncertainty remains important. The overall-survival hazard-ratio confidence intervals are broad. The investigator-assessed progression-free survival comparisons have confidence intervals that include 1. The response comparisons are unadjusted and their risk-difference confidence intervals span zero. The point estimates across these different endpoints do not form a simple, consistent basis for revising the interpretation of the primary result.

Secondary outcomes can add context by examining different dimensions of disease course and by using a different assessment process. They do not automatically confirm or overturn the primary endpoint: they may differ in definition, assessment, follow-up, and statistical precision. Investigator-assessed progression-free survival is also distinct from the blinded independent central review used for the primary outcome.

Multiple secondary endpoints and comparisons create multiplicity: the more questions tested, the greater the possibility of chance-positive results if each is treated as a separate confirmatory test. The registry record does not report a complete testing hierarchy or multiplicity adjustment. Consequently, unadjusted secondary results carry less confirmatory weight than a result analyzed under a clearly specified, controlled testing strategy. They are most appropriately read as supportive and exploratory evidence, with the limitations of their analysis and reporting kept in view.

Secondary outcomes registered for this trial, for reference (only those above were recalculated):

• Overall Survival
• Progression-Free Survival (PFS) as Assessed by Investigator
• Percentage of Participants With Objective Response as Assessed by Investigator
• Percentage of Participants With Objective Response as Assessed by Blinded Independent Central Review (BICR)
• Duration of Response (DOR) as Assessed by Investigator
• Duration of Response (DOR) as Assessed by Blinded Independent Central Review (BICR)
• Maintenance Progression-Free Survival as Assessed by Blinded Independent Central Review (BICR)
• Maintenance Progression-Free Survival (PFS) as Assessed by Investigator

9. Statistical Interpretation

10. Statistical Methods Explained

Time-to-event analysis is appropriate when an endpoint records the time until an event such as progression or death, and not all participants necessarily experience the event during observed follow-up. The registry describes progression-free survival as time from randomization until progression or death and reports use of the Kaplan-Meier method. Kaplan-Meier estimation accounts for right-censored observations: a participant contributes follow-up until the last time their event status is adequately known, without being counted as having had an event after that point.

What does censoring mean?

Censoring means the exact event time is not observed within the participant's usable follow-up. The record says primary endpoint data were censored at the last adequate tumor assessment for participants without an event, for participants who began new anti-cancer therapy before an event, or for participants with an event after at least two missing tumor assessments. The validity of a time-to-event estimate depends in part on how censoring relates to the chance of the event. The registry record describes its rules but does not report analyses testing the assumptions or alternative censoring approaches.

How should the hazard ratio be read?

A hazard ratio compares event rates over follow-up between groups. A value of 1 represents equal hazards under the model; values on either side of 1 indicate a relative difference in the event rate according to the comparison's coding. The trial reports hazard ratios and confidence intervals using a Log Rank method. The registry record does not give enough detail to reconstruct all analysis choices or explain the unusual pairing of the primary p-values with their reported estimates and confidence intervals. The posted sponsor results should therefore be presented as reported rather than replaced with a speculative reanalysis.

A hazard ratio is not a ratio of medians and does not directly state the difference in median time. It also does not describe the probability that an individual participant will experience an event. Its interpretation as a common relative effect over follow-up is most straightforward when the proportional-hazards assumption is reasonable, but checks of that assumption are not reported in the registry record.

What do medians and confidence intervals add?

The median time-to-event estimate is the time by which half of the estimated event-time distribution has experienced the event. It is a useful summary but does not describe the full shape of the event-time distribution. A confidence interval communicates uncertainty around an estimate. For the primary outcome, the registry posts median estimates for the two avelumab groups and incomplete median information for the observation group. The missing upper bounds are not reported in the registry record.

A confidence interval is not a range containing a known fraction of individual participant outcomes. It reflects uncertainty in an estimated quantity under the analysis method. Its width depends on features such as event information and variability. For comparisons, an interval that includes 1 for a hazard ratio does not rule out differences in either direction; it indicates that the estimate is compatible with that value under the interval procedure. The interval should be considered alongside the point estimate and the study's analysis context.

Why distinguish blinded review from investigator assessment?

The primary progression endpoint was assessed by blinded independent central review, while one secondary progression-free survival outcome was assessed by investigators. Independent blinded review can reduce the influence of knowledge of treatment assignment on endpoint assessment, especially in an open-label trial. Investigator assessment may reflect clinically informed local review, but assessors in an open-label study may know the assigned strategy. The two assessments can differ because they use different review processes; neither should be substituted for the other without explanation.

The registry also lists objective response assessed by investigators and by blinded independent central review, along with response duration and maintenance progression-free survival. These outcomes address different aspects of disease course. The posted secondary results include investigator-assessed outcomes, but detailed numerical results for every listed outcome are not reported in the registry record.

How should binary response comparisons be understood?

Objective response is a binary outcome for each participant: a response is counted or not counted under the outcome definition. The posted response proportions are descriptive, while the accompanying unadjusted recalculations express treatment-group contrasts with confidence intervals and unadjusted p-values. An unadjusted comparison does not account for multiplicity or necessarily adjust for baseline characteristics. These recalculations are not a substitute for a sponsor analysis, and the registry record does not post a sponsor analysis for these response comparisons.

Risk differences express an absolute contrast between response proportions, whereas risk ratios and odds ratios express relative contrasts. They are different measures and can give distinct impressions of an effect. The confidence intervals for the recalculated contrasts represent uncertainty under their corresponding methods. They should not be used to infer causal effects beyond the randomized comparison and its analysis population.

What does the Log Rank method contribute?

The Log Rank method compares time-to-event experience between groups across follow-up, using event timing and the groups at risk. It is commonly used in survival analysis. The hazard ratios and p-values reported in the registry are associated with this method. A p-value summarizes how compatible the data are with a specified null hypothesis under the method's assumptions; it is not the probability that the null hypothesis is true, nor does it measure clinical importance.

The registry labels the primary comparisons as superiority analyses. However, the full protocol, prespecified testing hierarchy, multiplicity adjustment, detailed statistical analysis plan, model diagnostics, and interim-analysis plan are not reported in the registry record. Those omissions limit what can be said about confirmatory status and the handling of repeated testing. The trial's original sample-size assumptions and justification are also not reported in the registry record.

11. Confidence Intervals and Precision

The precision of an estimate is conveyed chiefly by its confidence interval, not by the number of digits in the point estimate. For the primary comparisons, the reported 95% confidence intervals are 1.051 to 1.946 and 0.832 to 1.565. Both include 1, so the intervals retain uncertainty about the direction and size of the relative hazard. One interval lies above 1, while the other spans values on both sides of 1; neither should be interpreted apart from the reported p-value and the registry's analysis context.

The point estimate for chemotherapy followed by avelumab is 1.43, and for chemotherapy plus avelumab followed by avelumab maintenance it is 1.14. These numbers are not exact measures of a fixed underlying effect. The confidence intervals show that the estimates are uncertain, and the record does not provide enough information to determine whether the proportional-hazards assumption held or how the unusual reported p-values were generated.

Median estimates for the two avelumab groups have lower confidence bounds, but their upper confidence bounds are not reported in the registry record. For observation, the median estimate itself is not reported in the registry record. This incomplete reporting prevents a complete comparison of median precision among the three groups.

Secondary estimates also vary in precision. The overall-survival confidence intervals are wide, while the investigator-assessed progression-free survival intervals include 1. The response comparisons have confidence intervals that span zero for their risk differences. Such uncertainty means that the observed point estimates should not be treated as definitive estimates of a treatment effect.

In general, confidence intervals describe uncertainty under the assumptions of the method used. They do not account automatically for every source of uncertainty, including selection among many outcomes or analyses. The registry record does not report a complete multiplicity plan, and the posted precision should be read with that limitation in mind.

12. Planning a Similar Trial: Sample Size

This is a planning illustration, not a re-evaluation of the original trial. It asks: if a new study wanted to detect a difference like the one observed, or a smaller one, how large would it need to be? It is deliberately not “observed power” of the finished trial, which is not a meaningful quantity.

The planning illustrations use the observed effect as a reference and then consider planning for 100%, 75%, or 50% of that observed effect. For time-to-event outcomes, the entries are total events needed, not participants per arm. For other outcomes, they are participants per arm. The primary outcome entries therefore describe event totals for the specified power targets, while the response entries describe group sizes per arm.

The planning assumptions are a two-sided significance level of 0.05, equal allocation between the two arms, and a normal approximation. For time-to-event planning, the event totals use the Schoenfeld approach. The smaller the effect selected for planning, the more information is generally needed to distinguish it from the null under the same assumptions. In this illustration, the entries increase as planning moves from the observed effect to smaller fractions of it.

The 80% power column gives the illustrative number of events or participants needed for an 80% chance of detecting the specified effect under the stated assumptions, if that effect were the true one. The 90% power column represents a higher chance of detection and consequently calls for more information under the same assumptions. Power is a property of a planned design relative to a specified effect and analysis; it is not the probability that a finding is true.

These figures are planning illustrations based on observed effects, not the trial's original design justification. The trial's own design assumptions are not reported in the registry record. This is not observed power.

13. How the Sample Size Is Derived

Power is the probability that a study of a given size rejects the null hypothesis when a specific true effect exists. It depends on four things: the effect to detect, the variability of the outcome, the significance level (here a two-sided α of 0.05, so z_1−α/2 = 1.960) and the desired power (z_1−β = 0.842 for 80% and 1.282 for 90%).

Formula

d is the total number of events needed (Schoenfeld's formula) with 1:1 allocation and proportional hazards.

Worked calculation for this trial

1. Hazard ratio HR = 1.430, so ln(HR) = 0.3577.
2. d = 4 × (1.96 + 0.842)² / [ln(1.430)]² = 245.4, rounded up to 246 events in total for 80% power.

The smaller-effect rows in the table above repeat the same calculation with the effect multiplied by 0.75 and 0.5 (for ratios, applied to the logarithm of the ratio).

R code

alpha <- 0.05
z_a   <- qnorm(1 - alpha / 2)          # two-sided
hr <- 1.43                              # observed hazard ratio
events_needed <- function(power, frac = 1) ceiling(round(4 * (z_a + qnorm(power))^2 / log(hr^frac)^2, 6))   # Schoenfeld, 1:1 allocation
for (f in c(1, 0.75, 0.5))
  cat(sprintf("%3.0f%% of observed effect: events = %s (80%% power), %s (90%% power)\n", 100 * f,
              format(events_needed(0.80, f), big.mark = ","), format(events_needed(0.90, f), big.mark = ",")))

# Simulation: given d total events under proportional hazards, events in the treatment arm are Binomial(d, hr / (1 + hr)).
# The score (log-rank type) statistic is (D1 - d / 2) / sqrt(d / 4).
set.seed(2718417)
d    <- events_needed(0.80)
reps <- 20000
D1 <- rbinom(reps, d, hr / (1 + hr))
z  <- (D1 - d / 2) / sqrt(d / 4)
cat(sprintf("Simulated power with %s events: %.3f (%d replicates)\n", format(d, big.mark = ","), mean(abs(z) > z_a), reps))

Output from running the code

100% of observed effect: events = 246 (80% power), 329 (90% power)
 75% of observed effect: events = 437 (80% power), 585 (90% power)
 50% of observed effect: events = 982 (80% power), 1,315 (90% power)
Simulated power with 246 events: 0.788 (20000 replicates)

The simulation uses the fact that, with d events in total and proportional hazards, the number of events in the treatment arm is binomial. It is an approximation that conditions on the total number of events, and it should land close to the target power.

14. Analyses Reported by the Sponsor

The primary hazard ratios, confidence intervals, and p-values are reported in the registry as sponsor analyses using the Log Rank method. The registry's primary outcome description specifies Kaplan-Meier estimation for progression-free survival, and the comparison results are listed separately as hazard ratios. The posted results should be distinguished from simple unadjusted recalculations based on summary statistics, which do not replace the sponsor's analysis.

For the primary endpoint, the registry reports hazard ratios of 1.43 and 1.14 for the two avelumab comparisons, with corresponding p-values of 0.989 and 0.793. These reported estimates and tests are the basis for interpreting the sponsor's primary analysis. The registry record does not give further detail to reconcile the reported p-values with the associated estimates and confidence intervals, so the values should not be silently altered or recalculated from incomplete information.

The secondary response comparisons are presented as unadjusted recalculations and have no sponsor analyses posted in the record. They are useful as descriptive contrasts but are not equivalent to a prespecified sponsor analysis. The discrepancy indicator is false; no discrepancy between the reported analyses and recalculations is flagged in the registry data.

15. Multiplicity, Missing Data and Analysis Populations

Multiplicity arises when several outcomes, treatment comparisons, time points, or analyses are considered. Even when each test uses a conventional significance threshold, repeated testing can increase the chance of at least one apparently positive result by chance. This trial has three groups, multiple listed outcomes, and two primary comparisons against the observation group. The registry identifies the primary outcome and reports analyses for both comparisons, but a full prespecified testing hierarchy and multiplicity-control procedure are not reported in the registry record.

The registry lists 36 outcome measures and six analyses. Those counts alone do not establish how the outcomes were prioritized or which results were intended to support formal claims. The trial's detailed statistical analysis plan, interim-analysis plan, and original sample-size justification are not reported in the registry record. It is therefore not possible to infer a particular adjustment strategy or confirmatory sequence.

Missing-data handling is described for primary progression-free survival. The record specifies censoring at the last adequate tumor assessment for participants without an event, for participants who began new anti-cancer therapy before an event, and for participants with an event after at least two missed tumor assessments. The registry does not report sensitivity analyses evaluating alternative assumptions or how the results might change under other missing-data approaches.

The full analysis set included all randomized participants, but the registry record does not provide further detail in the primary population description about analysis-set exclusions, adherence, or protocol deviations. The record also does not describe baseline balance or the handling of missing covariates for the posted comparisons. These omissions matter because interpretation depends on both the endpoint data and the analysis population.

These gaps do not negate the posted analyses, but they limit independent assessment of how testing and missing information were handled. Conclusions should remain tied to the registry's reported endpoints and estimates rather than inferred design features.

16. Safety Results

The registry reports serious adverse events as affected participants divided by participants at risk.

Deaths

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: febrile neutropenia (3.0%), pyrexia (3.0%), ileus (2.7%), anaemia (2.4%), pulmonary embolism (2.1%).

The registry posts serious adverse event counts by treatment group. Among participants at risk, serious adverse events affected 92 of 328 in chemotherapy followed by avelumab, 118 of 329 in chemotherapy plus avelumab followed by avelumab, and 64 of 334 in chemotherapy followed by observation. These are participant counts, not a comparison adjusted for follow-up or other factors. The registry also posts death counts of 34, 31, and 20 for these groups, respectively; the record does not explain in this summary how those deaths relate to adverse-event classifications.

The most frequently listed serious adverse event terms include febrile neutropenia and pyrexia, each at 3.0%; ileus at 2.7%; anaemia at 2.4%; and pulmonary embolism and urinary tract infection, each at 2.1%. These term-specific percentages should not be treated as a complete account of all safety findings.

Raw counts do not establish comparative risk on their own. Interpretation may depend on exposure time, definitions, event ascertainment, severity grading, and the handling of repeated events. The registry record does not provide enough detail to assess those features or to make a causal comparison. These figures describe posted safety data; they are not individualized medical advice.

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

The registry reports primary progression-free survival estimates for two avelumab strategies compared with chemotherapy followed by observation. The hazard-ratio confidence intervals include 1, and the posted p-values are 0.989 and 0.793. These results do not provide a precise, unambiguous estimate of the relative hazard for either comparison. The registry record does not explain the relationship between these reported p-values and the corresponding estimates and confidence intervals.

The findings do not establish that the strategies are equivalent, nor do they establish that either is superior. A nonsignificant test, by itself, does not demonstrate equivalence or exclude potentially meaningful effects. Establishing equivalence or noninferiority would require a prespecified framework and margins, which are not reported in the registry record.

The primary endpoint concerns progression or death as defined and assessed in the trial. It does not directly answer every question about overall survival, response, quality of life, or other outcomes. The posted secondary evidence is incomplete and includes analyses with substantial uncertainty; it should not be treated as a substitute for a fully reported primary analysis plan.

The results apply to the randomized comparisons and population described in the record. The full analysis set included all randomized participants, and eligibility was limited to previously untreated patients with specified ovarian, fallopian tube, or primary peritoneal cancers who were candidates for platinum-based chemotherapy. Generalizing beyond that population requires evidence not contained in this registry record.

The trial is marked terminated, but the reason is not reported in the registry record. Termination status alone does not explain the study's outcome, the completeness of follow-up, or the basis for the posted analyses. The appropriate interpretation is therefore a cautious description of the results and their uncertainty, rather than a broad claim about treatment effectiveness.

18. Why This Trial Matters Statistically

This trial presents several statistical features that matter for interpreting randomized oncology studies. It compares two distinct ways of incorporating avelumab with a shared chemotherapy-and-observation group, so each comparison must be read separately. The primary endpoint is time-to-event and was assessed by blinded independent central review even though the study itself was open-label. That distinction is relevant because assessment procedures can influence how progression is recorded.

The results also illustrate why point estimates cannot stand alone. Hazard ratios are accompanied by confidence intervals and p-values, and the primary intervals include 1. The posted medians are incomplete for the observation group and have missing upper confidence bounds for the avelumab groups. A careful reading must preserve those limits rather than treating a single number as a complete summary.

Several secondary outcomes are listed, but a multiplicity strategy is not reported in the registry record. This matters because a large collection of outcomes can invite selective emphasis on individual estimates. Secondary results should be considered in the context of prespecification, testing hierarchy, and uncertainty, none of which is fully documented in the registry record.

Finally, the record distinguishes sponsor-reported time-to-event analyses from unadjusted response recalculations and gives limited information about the original design assumptions. These are not interchangeable forms of evidence. Keeping the endpoint definitions, analysis types, and reporting gaps visible is essential for avoiding overinterpretation of a complex clinical trial record.

19. 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.

Several trial-specific limitations in the registry record constrain interpretation. The study is marked terminated, but the reason for termination is not reported in the registry record. The record does not explain whether termination related to efficacy, safety, operational considerations, or another cause, so no explanation should be inferred from the status alone.

Primary progression-free survival results are incomplete for the observation group: its median estimate is not reported in the registry record, though a lower confidence bound is posted. The primary median results for the two avelumab groups also lack upper confidence bounds. This limits direct comparison of median estimates and their precision.

The registry reports two primary hazard-ratio comparisons and their p-values, but does not provide enough additional analysis detail to resolve the unusual relationship between those values and the confidence intervals. The detailed statistical analysis plan, original sample-size justification, planned interim analyses, model diagnostics, and multiplicity handling are not reported in the registry record.

Although censoring rules are described for the primary endpoint, sensitivity analyses for missing data and alternative censoring assumptions are not reported in the registry record. The record also does not provide complete numerical results for every listed secondary endpoint. The investigator-assessed response comparisons are unadjusted recalculations, not posted sponsor analyses, and should be treated accordingly.

These limitations concern what can be established from the registry record. They do not themselves show that the trial was conducted improperly, but they restrict independent assessment of its design choices, analysis plan, and the robustness of the posted results.

20. Related Tutorials

21. Related Statistical Calculators

22. Sources

• ClinicalTrials.gov: Avelumab in Previously Untreated Patients With Epithelial Ovarian Cancer (JAVELIN OVARIAN 100) — NCT02718417.
• Registry record last updated 2020-07-14; status last verified 2020-06.
• Results first posted 2019-12-18.
• 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.

23. Record Summary

JAVELIN OVARIAN 100 was a randomized, open-label, parallel-group Phase 3 study of avelumab strategies in previously untreated epithelial ovarian cancer and related cancers. Its three groups received chemotherapy followed by observation, chemotherapy followed by avelumab maintenance, or chemotherapy combined with avelumab followed by avelumab maintenance.

The primary outcome was progression-free survival assessed by blinded independent central review. The registry reports hazard ratios for each avelumab comparison with observation, along with confidence intervals and p-values. The confidence intervals include 1, and some median-result details are not reported in the registry record.

Secondary outcomes include overall survival, investigator-assessed progression-free survival, response, response duration, and maintenance progression-free survival. The posted secondary findings are incomplete and should be interpreted cautiously, particularly because the registry record does not report a full multiplicity plan or the original design assumptions. The trial status is terminated; the reason is not reported in the registry record.