Pivotal Study in HER2 Negative, Locally Recurrent or Metastatic Breast Cancer: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Pivotal Study in HER2 Negative, Locally Recurrent or Metastatic Breast Cancer (NCT03786094), a randomized phase 3 study. The primary outcome is Progression Free Survival (2nd Line+ Population).

2. Clinical Question

The registry describes the study as an international, multicenter, phase 3 randomized trial. Its stated purpose was to investigate efficacy, safety, and tolerability for the combination relative to eribulin alone. The primary comparison uses time-to-event data, so it concerns both whether an event occurred and how long participants remained without a recorded event under the endpoint definition. The posted results also include an overall-survival outcome in a 3rd Line+ population; that is a distinct population and endpoint, rather than another measure of the primary question.

3. Trial Design

This was a phase 3, randomized, open-label, active-controlled trial with a parallel-group design. Enrollment was 432. The registry lists 219 participants in the balixafortide-plus-eribulin group and 213 in the eribulin-monotherapy group for the primary endpoint. The study status is terminated. The reason for termination is not reported in the registry record.

The intervention group received balixafortide with eribulin, while the active-control group received eribulin monotherapy. No masking was used. The trial was conducted in patients with HER2-negative, locally recurrent or metastatic breast cancer. The primary endpoint analysis population is identified as Overall Population (2nd Line+); the secondary overall-survival outcome concerns the 3rd Line+ population. These population labels define the scope of the results and should not be treated as interchangeable.

The primary endpoint was progression-free survival, assessed by an Independent Review Committee and defined as time from randomization to the earliest documented progressive disease or death from any cause. The registry states that progression and response were evaluated according to RECIST v1.1. Treatment continued until progressive disease by RECIST v1.1 or until a treatment-discontinuation or study-withdrawal criterion was met. Specific randomization procedures, allocation concealment, stratification factors, treatment schedules, and the original statistical design assumptions are not reported in the registry record.

Open-label assignment means participants and study staff were not masked to the assigned treatment. Independent endpoint review is described for the primary progression-free-survival assessment, but the registry record does not give further details about the review process. The record lists a two-sided t-test as the reported analysis method for the hazard-ratio comparison. More detailed statistical procedures 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

Analysis population for the primary outcome, as defined in the registry: Overall Population (2nd Line+)

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: Overall Population (2nd Line+)

6. Primary Endpoint

The registry lists the primary outcome as Progression Free Survival (2nd Line+ Population), measured over Patients received treatment until PD by RECIST v1.1 criteria was met or until one of the treatment discontinuation or study withdrawal criteria was met..

Progression-free survival measures the time from randomization until the first of documented progressive disease or death from any cause. It is a time-to-event endpoint: participants can contribute information about both the occurrence and timing of an event, while participants without an observed event may be censored under the specified rules. The registry identifies the primary population as Overall Population (2nd Line+) and says the endpoint was assessed by an Independent Review Committee.

The endpoint was evaluated using RECIST v1.1 criteria for complete response, partial response, stable disease, and progressive disease. In general, progression-free survival is used to describe how long participants remain alive without documented disease progression under a defined assessment process. It can provide a time-sensitive measure of disease control without waiting for every participant to die. That general rationale does not establish that a particular treatment is beneficial, and the endpoint's interpretation depends on its definition, assessment schedule, censoring rules, and completeness of follow-up.

The reported median progression-free survival was 3.5 months for balixafortide plus eribulin, with an interval from 2.8 to 4.2 months, and 4.0 months for eribulin monotherapy, with an interval from 3.0 to 4.3 months. The medians describe the midpoint of the observed time-to-event distributions; they do not describe each participant's experience. The registry specifies censoring for several situations, including being alive without postbaseline assessments, loss to follow-up, withdrawal of consent, starting another anticancer therapy before documented progression, and an event documented after 2 or more missing tumor assessments.

7. Results Posted in the Registry

• Balixafortide + Eribulin vs Eribulin Monotherapy: hazard ratio 1.10 (95% CI 0.85–1.41), reported p = 0.445 (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 (3rd Line+ Population)

• Endpoint type: Time to event: compared as a hazard ratio.
• Test: Hazard ratio as reported by the sponsor (t-test, 2 sided); it was not recalculated.
• Result:
  • Balixafortide + Eribulin vs Eribulin Monotherapy: hazard ratio 1.08 (95% CI 0.66–1.77), reported p = 0.613 (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 Balixafortide + Eribulin vs Eribulin Monotherapy and the control. The interval gives the range of effects that remain compatible with the data.

The posted secondary outcome is overall survival in the 3rd Line+ population. Its population differs from the primary 2nd Line+ population, and overall survival is distinct from progression-free survival. The secondary estimate therefore adds information about a separate outcome and treatment-line group; it should not be treated as an independent confirmation of the primary comparison.

Across the primary and secondary time-to-event comparisons, the registry does not report a statistically compelling separation between treatment groups. The secondary hazard-ratio interval is broad and includes the equal-hazard reference, so it leaves uncertainty about the direction and size of the relative hazard. The secondary p-value also does not provide strong evidence against the no-difference reference. These statements describe the pattern of the results rather than establishing that the endpoints are equivalent.

Secondary outcomes are often interpreted with less weight than the primary outcome because they may be exploratory, may involve different populations, and may be examined alongside several other outcomes. If many hypotheses are tested without a prespecified multiplicity strategy, the chance of at least one apparently notable finding can rise. The registry record does not report whether secondary testing was adjusted, how testing was ordered, or which secondary analyses were confirmatory. The result should therefore be read as supportive descriptive evidence with uncertainty, not as a standalone basis for a firm conclusion about the primary question.

The overall pattern does not reverse or settle the primary interpretation. Both endpoint families remain subject to their own definitions, populations, follow-up, censoring, and analysis assumptions. The record does not provide enough information to assess whether the secondary analysis was prespecified or how missing survival status was handled beyond the stated monitoring procedure. The secondary findings consequently provide context, while leaving the primary comparison and its uncertainty central to interpretation.

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

• Overall Survival (3rd Line+ Population)

9. Statistical Interpretation

10. Statistical Methods Explained

What does a time-to-event result represent?

Progression-free survival is a time-to-event outcome. The event is the earliest documented progressive disease or death from any cause, and the clock begins at randomization. Participants who have not had a recorded event by the end of their observed follow-up can contribute censored information rather than a known event time. Censoring indicates that the event time is not observed within the available follow-up; it does not mean that an event could never occur.

The registry gives specific censoring circumstances, including being alive without postbaseline assessments, loss to follow-up, withdrawal of consent, starting anticancer therapy before documented progression, and an event recorded after 2 or more missing tumor assessments. These rules matter because the analysis relies on how event-free participants are handled. In general, time-to-event methods rely on assumptions about censoring and follow-up. Whether those assumptions are reasonable for this trial cannot be determined from the posted information alone.

How should the median be read?

The median is the time by which half of the estimated event-time distribution has experienced the event, under the analysis method used. It is a summary of the distribution, not a mean and not a statement that each participant had that duration. The posted median estimates are 3.5 months for the combination and 4.0 months for monotherapy. Their reported intervals are 2.8 to 4.2 months and 3.0 to 4.3 months, respectively. The intervals express uncertainty around the median estimates; they are not ranges containing every participant's progression-free time.

What does the hazard ratio add?

A hazard ratio compares event rates over follow-up under the model and analysis used. A hazard ratio of 1 is the reference for equal hazards; values on either side indicate the direction of the estimated relative hazard for the stated arm order. The posted primary estimate is 1.10 for balixafortide plus eribulin versus eribulin monotherapy. The reported interval is 0.85 to 1.41, and the reported p-value is 0.445. Because the interval includes 1, the result does not rule out equal hazards. The interval also includes values below and above 1, so it permits uncertainty in both directions.

A hazard ratio is not a ratio of the reported medians, and it does not mean that each participant's event time changes by a fixed proportion. It summarizes relative event rates across follow-up, subject to the analysis assumptions. The registry identifies the comparison method as a two-sided t-test, but does not describe the detailed model, its assumptions, or how the stated method was applied to the hazard ratio. Those details are not reported in the registry record.

How do p-values and intervals complement each other?

A p-value describes how unusual the observed data, or data more extreme, would be under a specified null hypothesis and analysis procedure. It is not the probability that the null hypothesis is true, and it does not measure the clinical importance of an estimate. The primary p-value is 0.445. The registry does not report the full prespecified testing procedure or whether the reported p-value was adjusted for other outcomes.

A confidence interval gives a range of values compatible with the data and the interval procedure. In repeated use of a valid procedure, intervals at the stated confidence level would cover the true value at the corresponding long-run rate. An interval is not a probability statement about the fixed true value after observing the data. The endpoint listing describes median dispersion as a 95% Confidence Interval. For the reported primary hazard-ratio analysis, the record lists a 96% confidence interval; for the secondary hazard-ratio analysis it lists a 99.9% confidence interval. The reason for these reported levels is not reported in the registry record.

What can and cannot be inferred?

The posted data describe the randomized groups and their estimated outcomes. Randomization is generally used to support a fair comparison by balancing prognostic factors on average, but the record does not report allocation details or baseline characteristics needed to assess the realized balance. Open-label assignment can affect care, reporting, and follow-up processes. Independent review is specified for the primary endpoint, but the record does not provide enough detail to evaluate the review procedures. These considerations do not invalidate the result automatically; they define the information needed to judge its robustness.

The original sample-size justification, assumptions about the treatment effect, interim analyses, and complete analysis plan are not reported in the registry record. The registry's separate planning illustration uses the observed effect and stated assumptions; it is not a record of the trial's original design. The distinction matters because a planning calculation based on an observed estimate cannot establish the trial's original power or explain the decisions made before enrollment.

11. Confidence Intervals and Precision

The primary median estimates are accompanied by reported intervals: 3.5 months, with an interval from 2.8 to 4.2 months, for balixafortide plus eribulin; and 4.0 months, with an interval from 3.0 to 4.3 months, for eribulin monotherapy. These intervals overlap. Overlap is a useful visual cue about uncertainty, but it is not itself a formal test of the difference between medians. The direct reported comparison is the hazard ratio.

For the primary hazard-ratio comparison, the estimate is 1.10 and the reported interval runs from 0.85 to 1.41. The interval includes the equal-hazard reference and spans values on both sides of it. This means that the point estimate should not be read as a precise determination of the direction or magnitude of the relative hazard. The reported p-value, 0.445, is consistent with substantial uncertainty in the comparison; it does not establish that the groups are equivalent.

Precision depends on the amount and distribution of event information, follow-up, and the analysis procedure, not only on the total enrollment. The registry record does not provide all details needed to assess those factors, including the complete event count and the full analysis plan. The trial's terminated status also makes the reason and its implications relevant, but the reason is not reported in the registry record. Overall, the result is best read as an estimate with uncertainty rather than as a definitive statement that the treatment groups have the same or different outcomes.

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 figures for the time-to-event outcomes are total event counts, not participants per arm. The illustration uses the observed effect as its starting point and considers planning for 100% of that observed effect, 75% of the observed effect, and 50% of the observed effect. For each assumed effect, the columns describe the total events needed for 80% power and for 90% power. The primary-outcome illustration reports 3,457 total events and 4,627 total events for planning at 100% of the observed effect; 6,145 and 8,226 for 75%; and 13,825 and 18,508 for 50%. These are planning illustrations, not outcomes observed in the trial.

The stated calculation assumptions are a two-sided significance level of 0.05, equal allocation between the two arms, and a normal approximation. The event-count calculation uses the Schoenfeld method. The figures are not participants per arm because time-to-event planning is expressed in total events. In general, 80% power means that, if the assumed effect and analysis conditions were true, the design would have an 80% chance of detecting an effect under the specified testing procedure; 90% power describes the corresponding 90% chance. Greater power requires more event information under otherwise similar assumptions.

Planning for a smaller effect requires more participants and, for a time-to-event outcome, more total events. That is why the event requirements increase as the assumed fraction of the observed effect becomes smaller. These counts do not say how many participants would be needed in a particular setting without further assumptions about follow-up and event occurrence. The original trial's sample-size assumptions and justification 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 = 1.100, so ln(HR) = 0.0953.
2. d = 4 × (1.96 + 0.842)² / [ln(1.100)]² = 3,456.1, rounded up to 3,457 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 <- 1.1                              # 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(3786094)
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 = 3,457 (80% power), 4,627 (90% power)
 75% of observed effect: events = 6,145 (80% power), 8,226 (90% power)
 50% of observed effect: events = 13,825 (80% power), 18,508 (90% power)
Simulated power with 3,457 events: 0.793 (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 sponsor-reported primary analysis gives a hazard ratio of 1.10 for balixafortide plus eribulin versus eribulin monotherapy, with an interval from 0.85 to 1.41 and p = 0.445. The posted comparison carries the same estimate, interval, and p-value, so the comparison shown in the registry record agrees with the sponsor's reported analysis. No discrepancy is indicated in the record.

The registry labels the analysis method as a two-sided t-test and identifies the parameter as a hazard ratio. It does not provide additional detail about the calculation or the model. The record gives a 96% confidence level for the primary hazard-ratio interval, while the endpoint description lists 95% intervals for the median estimates. These are separate summaries with different reported confidence levels; the reason for the hazard-ratio interval level is not reported in the registry record.

Where a sponsor analysis and a simple unadjusted recalculation differ, the sponsor's own analysis takes precedence. For this trial, the record does not flag a discrepancy, and no alternative recalculated primary estimate needs to replace the sponsor's reported result. The sponsor's estimate remains subject to the reported uncertainty and to limitations in the analysis details available in the registry.

15. Multiplicity, Missing Data and Analysis Populations

The registry record does not report a multiplicity plan. It does not state whether the primary and secondary outcomes were tested in a fixed sequence, whether any p-values were adjusted, or how the family of hypotheses was defined. Multiplicity matters because examining several endpoints or populations can increase the chance of at least one result appearing notable by chance. Without the prespecified strategy, the nominal p-values should not be assumed to control an overall error rate across all reported comparisons.

The primary endpoint description specifies several censoring situations. Participants could be censored if alive without postbaseline assessments, lost to follow-up, withdrawn from consent, started on another anticancer therapy before documented progression, or had an event documented after 2 or more missing tumor assessments. These rules are important because they determine which observations count as events and which contribute incomplete follow-up. The registry does not report sensitivity analyses comparing alternative censoring choices or detailed numbers of participants censored for each reason.

For overall survival, the investigator monitored status every 6 months or more frequently until death, withdrawal of consent to survival follow-up, or loss to follow-up. Further details about the handling of missing survival status are not reported in the registry record. The record also does not describe imputation, missing-data sensitivity analyses, or the completeness of endpoint assessments. These omissions do not show that the analysis was necessarily biased, but they limit independent evaluation of how missingness could affect the estimates.

The reported primary population is Overall Population (2nd Line+), while the secondary population is 3rd Line+. The registry record does not provide a full account of analysis-population rules, protocol deviations, or the handling of participants who did not contribute endpoint data. It also does not report interim-analysis procedures, stopping rules, or a full statistical analysis plan. The trial's termination reason is not reported. These missing details constrain assessment of prespecification and robustness.

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 (4.4%), pneumonia (2.5%), covid-19 pneumonia (2.5%), disease progression (2.5%), infusion related reaction (2.3%).

The safety results use different at-risk counts from the randomized primary endpoint groups. Serious adverse events were reported for 218 participants at risk in the balixafortide-plus-eribulin group, with 62 affected, and 204 at risk in the eribulin-monotherapy group, with 54 affected. Other adverse events were reported for 218 at risk, with 214 affected, in the combination group, and 204 at risk, with 197 affected, in the monotherapy group. Death counts were 17 and 13, respectively. These are counts as posted, not adjusted comparisons.

The registry lists febrile neutropenia at 4.4%, pneumonia at 2.5%, COVID-19 pneumonia at 2.5%, disease progression at 2.5%, infusion related reaction at 2.3%, and pleural effusion at 1.8% among the leading serious-event terms. A listed term's frequency does not by itself establish that the treatment caused the event. Nor do the counts alone compare risk fairly without considering follow-up, exposure, definitions, and the population included in each safety group.

The record does not provide detailed event-level timing, duration, severity distributions, attribution, or exposure-adjusted rates. Safety counts should therefore be read as descriptive registry results, not as a definitive comparative safety analysis.

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

The posted primary results describe progression-free survival in the Overall Population (2nd Line+). The median was 3.5 months with balixafortide plus eribulin and 4.0 months with eribulin monotherapy. The reported hazard ratio was 1.10, with an interval from 0.85 to 1.41 and p = 0.445. These estimates do not show a statistically compelling separation, and the interval leaves room for uncertainty in either direction. They do not establish that the treatments are equivalent.

The results also do not prove that the combination has no effect. A non-significant p-value can occur when the true effect is absent, when the effect is small, or when the available data are not sufficiently precise to distinguish effects. The confidence interval helps communicate that uncertainty, but it does not resolve it. The estimate is a comparison of the randomized groups under the registry's endpoint definition and analysis, not an individualized prediction.

Overall survival in the 3rd Line+ population is a secondary, distinct result. It cannot be substituted for the primary progression-free-survival analysis, and it does not by itself confirm or refute the primary result. Interpretation of both outcomes is limited by the unreported multiplicity plan, incomplete detail about missing-data analyses, and the absence of a full statistical analysis plan in the registry record.

The trial was randomized, which supports a comparative interpretation, but it was open-label and the registry does not report the detailed allocation process or baseline balance. Independent Review Committee assessment is specified for the primary endpoint, but further review procedures are not described. The trial status is terminated, and the reason is not reported in the registry record. Taken together, the posted data support a cautious description of the estimates and their uncertainty; they do not justify medical advice or a broad claim that either treatment works or does not work.

18. Why This Trial Matters Statistically

This trial illustrates why a time-to-event comparison should not be reduced to a single median. The primary endpoint includes timing and event information, while the hazard ratio summarizes relative event rates across follow-up. The medians, hazard ratio, interval, and p-value answer related but nonidentical statistical questions. Reading them together makes clear that the point estimates are not precise enough to establish a definitive direction of difference.

The case also highlights the importance of population definitions. The primary progression-free-survival result concerns the 2nd Line+ population, whereas the posted overall-survival outcome concerns the 3rd Line+ population. Results from different treatment-line populations cannot be treated as directly interchangeable. Endpoint definitions, censoring rules, and assessment procedures also shape what the estimates mean.

Finally, a registry result has limits as a statistical record. The trial is identified as randomized and open-label, and the primary endpoint is described in detail, but important parts of the analysis plan are not reported. The stated planning illustration is based on the observed effect and is not the trial's original design justification. This distinction helps prevent retrospective planning calculations from being mistaken for evidence about the original study's statistical power. The trial offers a useful example of interpreting an uncertain estimate without turning a non-significant result into proof of no effect.

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.

The registry record identifies the trial as terminated but does not report why. Without the reason and timing in context, it is difficult to assess whether termination affected recruitment, follow-up, endpoint maturity, or interpretation. The record lists enrollment of 432, but does not provide the original sample-size justification or the assumptions used in the trial's design. The planning illustration based on the observed effect cannot fill that gap.

The trial was open-label, and allocation concealment and randomization details are not reported in the registry record. Independent Review Committee assessment is stated for the primary endpoint, but the record does not describe the review process or whether all assessments were available for review. The analysis method is labeled as a two-sided t-test for the hazard-ratio comparison, without enough detail to reconstruct the analysis or assess its assumptions.

The primary endpoint has specified censoring rules, but detailed counts by censoring reason and sensitivity analyses are not reported. The record also does not describe a multiplicity plan, interim analyses, stopping rules, or the complete statistical analysis plan. These omissions limit assessment of prespecification and robustness. The primary and secondary outcomes concern different treatment-line populations, which further limits direct comparison between them.

Safety results are descriptive counts, with no exposure-adjusted comparisons or detailed attribution information reported. The available record therefore does not establish whether observed events were caused by a particular treatment or permit a full comparative safety assessment. These limitations define what can be concluded from the posted record; they are not evidence that unreported analyses were or were not performed.

20. Related Tutorials

21. Related Statistical Calculators

22. Sources

• ClinicalTrials.gov: Pivotal Study in HER2 Negative, Locally Recurrent or Metastatic Breast Cancer — NCT03786094.
• Registry record last updated 2023-11-01; status last verified 2023-10.
• Results first posted 2023-11-01.
• 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

NCT03786094 is a phase 3, randomized, open-label, parallel-group trial of balixafortide plus eribulin versus eribulin monotherapy in HER2-negative locally recurrent or metastatic breast cancer. Enrollment was 432, and the record lists the trial status as terminated. The reason for termination is not reported in the registry record.

The primary endpoint was progression-free survival in the Overall Population (2nd Line+), assessed by an Independent Review Committee. Median progression-free survival was 3.5 months with the combination and 4.0 months with monotherapy. The reported hazard ratio was 1.10, with an interval from 0.85 to 1.41 and p = 0.445. The posted estimate is uncertain and does not establish equivalence.

The record also posts overall survival for a 3rd Line+ population. The multiplicity plan, original sample-size justification, interim procedures, and full statistical analysis plan are not reported. The results are best interpreted as registry-reported estimates with important uncertainty and limitations in the available analysis detail.