This page provides an independent statistical analysis and educational interpretation of publicly reported results. ClinicalTrials.gov provides the official trial registry record.
1. Trial at a Glance
ASCENT was a randomized, parallel-group, open-label phase 3 trial with 529 participants. The primary registered endpoint was progression-free survival (PFS) by Independent Review Committee (IRC) assessment in the brain metastasis-negative (BM-ve) population. The registry reports formal statistical analyses for the primary endpoint and multiple secondary endpoints.
| Feature | ASCENT |
|---|---|
| Trial name | ASCENT |
| ClinicalTrials.gov identifier | NCT02574455 |
| Phase | Phase 3 |
| Status | Completed |
| Therapeutic area | Oncology |
| Condition | Breast Cancer |
| Allocation | Randomized |
| Design model | Parallel |
| Masking | None |
| Primary purpose | Treatment |
| Enrollment | 529 |
| Lead sponsor | Gilead Sciences |
| Sponsor type | Industry |
| Results posted | Yes |
| Outcome measures posted | 14 |
| Statistical analyses posted | 12 |
2. Clinical Question
The registered trial evaluates sacituzumab govitecan against Treatment of Physician's Choice in participants with refractory or relapsed metastatic triple-negative breast cancer. Statistically, the principal question is whether the randomized treatment comparison changes the time from randomization to objective tumor progression or death in the prespecified BM-ve population.
Population
Participants with refractory or relapsed metastatic triple-negative breast cancer. The primary analysis population was the BM-ve Population: randomized participants in strata with no baseline brain metastasis.
Intervention
Sacituzumab govitecan.
Comparator
Treatment of Physician's Choice (TPC).
Primary question
Does sacituzumab govitecan alter progression-free survival relative to TPC in the BM-ve population?
3. Trial Design
Sacituzumab govitecan
- Sacituzumab govitecan
- Randomized treatment arm
Treatment of Physician's Choice
- Treatment of Physician's Choice (TPC)
- Registry intervention list includes eribulin, capecitabine, gemcitabine and vinorelbine
Trial timeline
Trial start
The registry lists November 7, 2017 as the trial start date.
Primary completion
The registry lists March 30, 2020 as the primary completion date.
Results posted
ClinicalTrials.gov reports posted outcome measures and statistical analyses for the completed trial.
4. Endpoints
The registry identifies one primary endpoint and multiple secondary endpoints. The primary endpoint is a time-to-event measure; the posted secondary analyses include additional time-to-event and binary outcomes.
| Endpoint | Population | Registry time frame | Type |
|---|---|---|---|
| Primary: Progression-Free Survival (PFS) by Independent Review Committee (IRC) Assessment in Brain Metastasis Negative (BM-ve) Population | BM-ve Population | From randomization until objective tumor progression or death (assessed every 6 weeks for 9 months and then every 9 weeks thereafter until the occurrence of progression of disease; maximum exposure: 29.6 months) | Time-to-event |
| PFS by IRC Assessment in the ITT Population | ITT Population | From randomization until objective tumor progression or death (assessed every 6 weeks for 9 months and then every 9 weeks thereafter until the occurrence of progression of disease; maximum exposure: 29.6 months) | Time-to-event |
| Overall Survival (OS) in BM-ve Population | BM-ve Population | From the randomization to death from any cause (maximum follow-up duration: 30.8 months) | Time-to-event |
| Overall Survival (OS) in ITT Population | ITT Population | From the randomization to death from any cause (maximum follow-up duration: 30.8 months) | Time-to-event |
| Objective Response Rate (ORR) by IRC and Investigator Assessment in BM-ve Population | BM-ve Population with available data | From randomization to the date of progression or death (assessed every 6 weeks for 9 months and then every 9 weeks thereafter until the occurrence of progression of disease; maximum exposure: 29.6 months) | Binary |
| Duration of Response (DOR) by IRC and Investigator Assessment in BM-ve Population | BM-ve Population with objective response | From the first date of documented response of CR or PR to the date of progression or death (assessed every 6 weeks for 9 months and then every 9 weeks thereafter until the occurrence of progression of disease; maximum exposure: 29.6 months) | Time-to-event |
| Time to Progression (TTP) by Investigator Assessment in BM-ve Population | BM-ve Population | From randomization until disease progression (assessed every 6 weeks for 9 months and then every 9 weeks thereafter until the occurrence of progression of disease; maximum exposure: 29.6 months) | Time-to-event |
| Time to Progression (TTP) by IRC Assessment in BM-ve Population | BM-ve Population | From randomization until disease progression (assessed every 6 weeks for 9 months and then every 9 weeks thereafter until the occurrence of progression of disease; maximum exposure: 29.6 months) | Time-to-event |
| Clinical Benefit Rate (CBR) by IRC and Investigator Assessment in BM-ve Population | BM-ve Population | From randomization to the date of progression or death (assessed every 6 weeks for 9 months and then every 9 weeks thereafter until the occurrence of progression of disease; maximum exposure: 29.6 months) | Binary |
5. Analysis Populations
| Population | Registry definition / role |
|---|---|
| BM-ve Population | Included all randomized participants who were randomized to the strata of no baseline brain metastasis at the time of randomization. |
| ITT Population | Included all randomized participants. |
| BM-ve population with available data | Used for the posted ORR analyses. |
| BM-ve population with objective response | Used for the posted DOR analyses. |
The distinction between the BM-ve population and the ITT population is statistically important. The primary endpoint was not analyzed in every randomized participant indiscriminately; it was defined for the randomized participants belonging to the no-baseline-brain-metastasis strata. By contrast, the registry separately reports PFS and OS analyses in the full ITT population.
6. Primary Endpoint Result: Progression-Free Survival
The primary registered endpoint was PFS by IRC assessment in the BM-ve population. The registry reports a two-sided log-rank analysis comparing sacituzumab govitecan with TPC.
Primary PFS hazard ratio
95% CI: 0.305–0.492 · P < 0.0001
Analysis: log-rank test · Population: BM-ve
| Primary endpoint | Sacituzumab govitecan vs TPC |
|---|---|
| Effect measure | Hazard ratio |
| Estimate | 0.387 |
| 95% CI | 0.305–0.492 |
| P-value | <0.0001 |
| Statistical method | Log-rank test |
| Analysis population | BM-ve Population |
The estimated hazard ratio of 0.387 is below 1, indicating a lower estimated instantaneous rate of progression or death in the sacituzumab govitecan group relative to TPC under the time-to-event analysis. Expressed as a simple relative-hazard transformation, 1 − 0.387 = 0.613, so the estimate corresponds to an approximately 61.3% lower estimated hazard.
The hazard ratio does not mean that 61.3% of participants avoided progression, that every participant experienced the same reduction, or that the probability of progression or death was reduced by exactly 61.3% at every time point. It is a relative time-to-event measure rather than an absolute risk difference.
The 95% confidence interval of 0.305–0.492 describes uncertainty around the estimated hazard ratio under the analysis framework. It is an interval for the treatment-effect estimate, not a range containing the individual treatment effects experienced by patients.
The P-value of <0.0001 addresses the evidence against the null hypothesis represented by the statistical test. It does not measure the size or clinical importance of the effect. Effect magnitude is better described by the hazard ratio and its confidence interval, together with absolute event-time measures when those are available.
Because this is a time-to-event analysis, interpretation also depends on censoring and on the assumptions underlying the hazard-ratio framework. The ClinicalTrials.gov record does not report a proportional-hazards diagnostic, so the HR should not be interpreted as proving that the relative hazard was constant throughout follow-up.
7. Secondary Progression-Free Survival Analysis
The registry also reports PFS by IRC assessment in the full ITT population. This provides a useful comparison with the primary BM-ve analysis because the ITT population includes all randomized participants.
ITT PFS hazard ratio
95% CI: 0.330–0.517 · P < 0.0001
Analysis: log-rank test · Population: ITT
The ITT PFS estimate of 0.413 indicates a lower estimated hazard of progression or death in the sacituzumab govitecan group relative to TPC. The estimate corresponds to an approximately 58.7% lower estimated hazard because 1 − 0.413 = 0.587.
The 95% CI of 0.330–0.517 indicates the statistical uncertainty surrounding that estimate. It does not provide a prediction interval for individual patients and should not be read as saying that the treatment effect for every patient lies within that range.
The P-value of <0.0001 provides evidence against the null hypothesis used by the log-rank test; it does not quantify the magnitude of benefit. The hazard ratio and confidence interval provide the principal information about relative effect size and precision.
8. Overall Survival Results
Overall Survival in the BM-ve Population
BM-ve OS hazard ratio
95% CI: 0.390–0.592 · P < 0.0001
Maximum follow-up duration: 30.8 months
The BM-ve OS hazard ratio of 0.481 indicates a lower estimated instantaneous rate of death for sacituzumab govitecan relative to TPC in the analyzed BM-ve population. The simple relative-hazard interpretation corresponds to an approximately 51.9% lower estimated hazard.
The 95% CI of 0.390–0.592 describes uncertainty around the estimated relative hazard. It does not state the probability that the true effect lies in the interval, nor does it describe individual patient outcomes.
The P-value of <0.0001 is evidence from the specified statistical test and is not an effect-size measure. The absence of a median OS value in the ClinicalTrials.gov record means that a median-survival comparison should not be inferred from the hazard ratio alone.
Overall Survival in the ITT Population
ITT OS hazard ratio
95% CI: 0.422–0.625 · P < 0.0001
Maximum follow-up duration: 30.8 months
The ITT OS hazard ratio of 0.514 indicates a lower estimated hazard of death in the sacituzumab govitecan group relative to TPC. The estimate corresponds to an approximately 48.6% lower estimated hazard.
The 95% CI of 0.422–0.625 quantifies uncertainty around the estimated hazard ratio. It does not establish that the treatment reduces the probability of death by the same percentage at every follow-up time.
The P-value of <0.0001 addresses statistical evidence under the reported test. It should be considered alongside the magnitude and precision of the estimated effect rather than treated as a measure of clinical importance.
| Endpoint | Population | HR | 95% CI | P-value |
|---|---|---|---|---|
| Progression-Free Survival | BM-ve | 0.387 | 0.305–0.492 | <0.0001 |
| Progression-Free Survival | ITT | 0.413 | 0.330–0.517 | <0.0001 |
| Overall Survival | BM-ve | 0.481 | 0.390–0.592 | <0.0001 |
| Overall Survival | ITT | 0.514 | 0.422–0.625 | <0.0001 |
9. Objective Response Rate
ORR was analyzed as a binary endpoint in the BM-ve population. The registry reports separate analyses according to IRC assessment and investigator assessment, using the Cochran-Mantel-Haenszel method and odds ratios as the effect measure.
| ORR analysis | Method | Odds ratio | 95% CI | P-value |
|---|---|---|---|---|
| IRC assessment | Cochran-Mantel-Haenszel | 10.859 | 5.590–21.095 | <0.0001 |
| Investigator assessment | Cochran-Mantel-Haenszel | 7.363 | 4.063–13.341 | <0.0001 |
IRC-assessed ORR
95% CI: 5.590–21.095 · P < 0.0001
The IRC analysis estimates the odds of objective response to be 10.859 times the odds in the comparator group under the reported model. The corresponding 95% confidence interval is 5.590–21.095.
An odds ratio is not a risk ratio. An OR of 10.859 means the estimated odds of response were substantially higher in the sacituzumab govitecan group relative to TPC; it does not mean that 10.859 times as many participants responded.
The 95% CI of 5.590–21.095 describes uncertainty around the odds-ratio estimate. The interval remains above 1, consistent with the reported P-value of <0.0001.
The ClinicalTrials.gov record reports the OR and P-value but do not provide the underlying response percentages. Therefore, an absolute response-rate difference cannot be calculated from the ClinicalTrials.gov record without introducing information outside the permitted trial dataset.
Investigator-assessed ORR
95% CI: 4.063–13.341 · P < 0.0001
The investigator-assessed ORR analysis produced an odds ratio of 7.363. This represents substantially higher estimated odds of response in the sacituzumab govitecan group relative to TPC under the reported analysis.
The 95% CI of 4.063–13.341 quantifies uncertainty around the odds ratio. As with the IRC analysis, it cannot be translated directly into a percentage-point response-rate difference without the underlying group-specific response proportions.
The two ORR analyses are based on different assessment sources. Their estimates should therefore be understood as separate analyses rather than treated as two independent confirmations that can simply be averaged.
10. Duration of Response
DOR was analyzed among BM-ve participants with objective response. The registry reports separate IRC and investigator assessments using log-rank tests and hazard ratios.
| DOR analysis | HR | 95% CI | P-value |
|---|---|---|---|
| IRC assessment | 0.407 | 0.150–1.107 | 0.0683 |
| Investigator assessment | 0.212 | 0.103–0.435 | <0.0001 |
DOR by IRC Assessment
IRC-assessed DOR hazard ratio
95% CI: 0.150–1.107 · P = 0.0683
The IRC-assessed DOR hazard ratio of 0.407 is below 1, corresponding to an approximately 59.3% lower estimated hazard of progression or death among responders under this analysis.
However, the 95% CI of 0.150–1.107 crosses 1, and the reported P-value is 0.0683. The estimate therefore has considerably greater statistical uncertainty than the primary PFS estimate. The point estimate alone should not be interpreted as establishing a definitive difference in DOR.
DOR is also a responder-only endpoint. Its analysis population is not the same as the ITT population, so it answers a different question from the primary PFS analysis.
DOR by Investigator Assessment
Investigator-assessed DOR hazard ratio
95% CI: 0.103–0.435 · P < 0.0001
The investigator-assessed DOR hazard ratio of 0.212 corresponds to an approximately 78.8% lower estimated hazard of progression or death among responders in the treatment group.
The 95% CI of 0.103–0.435 indicates uncertainty around the estimated relative hazard while remaining below 1. The P-value of <0.0001 provides evidence against the null hypothesis used by the reported test.
The difference between the IRC and investigator estimates illustrates why assessment source matters. It is not appropriate to treat the larger numerical treatment effect from one assessment method as automatically establishing a stronger overall conclusion.
11. Time to Progression
The registry reports TTP separately by investigator and IRC assessment in the BM-ve population. Unlike PFS, TTP is defined around disease progression rather than progression or death in the registry-reported endpoint descriptions.
| TTP analysis | Method | HR | 95% CI | P-value |
|---|---|---|---|---|
| Investigator assessment | Log-rank test | 0.317 | 0.248–0.404 | <0.0001 |
| IRC assessment | Log-rank test | 0.406 | 0.315–0.525 | <0.0001 |
The investigator-assessed TTP hazard ratio of 0.317 corresponds to an approximately 68.3% lower estimated hazard of progression. The IRC-assessed TTP hazard ratio of 0.406 corresponds to an approximately 59.4% lower estimated hazard of progression. Both confidence intervals remain below 1, and both reported P-values are <0.0001.
12. Clinical Benefit Rate
CBR was analyzed as a binary endpoint in the BM-ve population using the Cochran-Mantel-Haenszel method. The registry reports separate IRC and investigator assessments.
| CBR analysis | Method | Odds ratio | 95% CI | P-value |
|---|---|---|---|---|
| IRC assessment | Cochran-Mantel-Haenszel | 8.543 | 5.055–14.437 | <0.0001 |
| Investigator assessment | Cochran-Mantel-Haenszel | 7.492 | 4.540–12.364 | <0.0001 |
The IRC-assessed CBR analysis produced an odds ratio of 8.543, with a 95% CI of 5.055–14.437. The investigator-assessed analysis produced an odds ratio of 7.492, with a 95% CI of 4.540–12.364. Both analyses reported P < 0.0001.
Both CBR estimates are odds ratios, so they describe relative odds rather than absolute probabilities. An OR of 8.543 does not mean that 85.43% of participants benefited, nor does it mean that the absolute benefit was 8.543 times larger.
The confidence intervals remain above 1 for both assessment methods. The consistency between the IRC and investigator estimates is descriptive evidence that the direction of the binary endpoint comparison was similar under the two assessment sources, although the analyses remain distinct.
13. Statistical Methodology
Log-rank test for time-to-event endpoints
The registry identifies the log-rank test as the reported method for PFS, OS, DOR and TTP analyses. The log-rank test compares the survival experience of two groups across observed event times while incorporating right-censored observations.
The test evaluates evidence for a difference between the time-to-event distributions. It does not itself produce the hazard ratio; the HR is the accompanying effect measure reported for these analyses.
Hazard ratio
The hazard ratio is a relative measure comparing the instantaneous event rate between two groups. Values below 1 indicate a lower estimated event hazard in the numerator group relative to the comparator under the fitted time-to-event framework.
An HR below 1 therefore indicates a lower estimated hazard in the sacituzumab govitecan group. It is not equivalent to a risk ratio, odds ratio, absolute risk difference, or probability of being progression-free.
Kaplan-Meier estimation
Time-to-event endpoints such as PFS, OS, DOR and TTP are naturally suited to Kaplan-Meier estimation because participants can have different lengths of follow-up and may be censored before experiencing the event. The ClinicalTrials.gov record does not provide the Kaplan-Meier curves or the underlying event-by-time dataset, so this page does not reconstruct a curve.
Here, di is the number of events at an event time and ni is the number at risk immediately before that time.
Cochran-Mantel-Haenszel test
The registry identifies the Cochran-Mantel-Haenszel method for the binary ORR and CBR analyses. This framework can compare treatment groups across categorical strata while accounting for the stratification structure represented in the analysis.
Odds ratios
For the binary endpoints, the registry reports odds ratios rather than risk ratios. The odds of an event are defined as the probability of the event divided by the probability of no event. Consequently, the odds ratio can differ substantially from a risk ratio when the outcome is not rare.
Intention-to-treat analysis
The registry explicitly identifies the ITT population as including all randomized participants and reports ITT analyses for PFS and OS. The ITT principle preserves the comparison created by randomization by analyzing participants according to randomized assignment rather than restricting efficacy analysis to participants who remain on treatment.
14. Statistical Methods Explained
Why was the primary endpoint analyzed with a log-rank test?
PFS is a time-to-event endpoint. Some participants progress or die while others remain event-free at the end of their available follow-up and are therefore censored. The log-rank test is designed to compare two such time-to-event distributions while incorporating the information contributed before censoring.
What does a hazard ratio of 0.387 mean?
It means that the estimated instantaneous rate of progression or death was 0.387 times the corresponding rate in the TPC group under the reported analysis. Equivalently, the simple transformation 1 − 0.387 gives an approximately 61.3% lower estimated hazard. It does not mean that 61.3% of participants avoided an event.
Why is the confidence interval important?
The point estimate alone does not communicate how precisely the treatment effect was estimated. The primary PFS 95% CI of 0.305–0.492 shows the uncertainty around the reported HR. A narrower interval generally indicates greater statistical precision than a wider interval, although precision and clinical importance are separate concepts.
Why doesn't a P-value measure treatment-effect size?
A P-value describes how compatible the observed data are with the null hypothesis used by the statistical test. It depends on both the size of the observed effect and the amount of information available. Therefore, a very small P-value does not mean that an effect is necessarily large, clinically important, or relevant to every patient.
Why does the BM-ve population matter?
The primary endpoint was specifically defined for participants randomized to strata with no baseline brain metastasis. This means the primary HR of 0.387 describes that prespecified analysis population, not automatically every participant enrolled in the trial. The separate ITT PFS analysis addresses the broader randomized population.
Why are IRC and investigator assessments reported separately?
Objective tumor response and progression can involve assessment procedures and judgment. Reporting IRC and investigator analyses separately allows readers to see whether the estimated treatment effect is similar across assessment sources. In ASCENT, the ClinicalTrials.gov record shows separate estimates for ORR, DOR, TTP and CBR according to assessment source.
Why is DOR analyzed only among responders?
DOR begins at the first documented response, so a participant must first have an objective response to enter the DOR analysis population. This makes DOR a different estimand from ITT PFS or OS, which begin at randomization. Consequently, DOR should not be interpreted as a substitute for a randomized comparison of all participants.
15. Interpreting Relative Effects Across Endpoints
| Endpoint | Effect measure | Estimate | What the estimate describes |
|---|---|---|---|
| Primary PFS, BM-ve | Hazard ratio | 0.387 | Relative hazard of progression or death |
| PFS, ITT | Hazard ratio | 0.413 | Relative hazard of progression or death |
| OS, BM-ve | Hazard ratio | 0.481 | Relative hazard of death |
| OS, ITT | Hazard ratio | 0.514 | Relative hazard of death |
| ORR, IRC | Odds ratio | 10.859 | Relative odds of objective response |
| ORR, investigator | Odds ratio | 7.363 | Relative odds of objective response |
| DOR, IRC | Hazard ratio | 0.407 | Relative hazard of progression or death among responders |
| DOR, investigator | Hazard ratio | 0.212 | Relative hazard of progression or death among responders |
| TTP, investigator | Hazard ratio | 0.317 | Relative hazard of progression |
| TTP, IRC | Hazard ratio | 0.406 | Relative hazard of progression |
| CBR, IRC | Odds ratio | 8.543 | Relative odds of clinical benefit |
| CBR, investigator | Odds ratio | 7.492 | Relative odds of clinical benefit |
These estimates should not be placed on a single numerical scale. A hazard ratio and an odds ratio have different mathematical meanings and refer to different endpoint structures. Even two hazard ratios can answer different questions when one concerns OS, another PFS, and another DOR among responders.
16. Safety Results
The ClinicalTrials.gov record reports serious adverse events by randomized treatment arm. The data do not provide a broader table of individual adverse-event categories, grades, or treatment-related events, so those outcomes are not added here.
| Safety measure | Sacituzumab govitecan | TPC |
|---|---|---|
| Serious adverse events | 69/258 | 64/224 |
The reported counts are presented as affected participants over participants at risk. The ClinicalTrials.gov record does not state a formal statistical comparison of serious adverse-event rates, so no inferential P-value or relative safety effect is added.
17. What the Primary Result Does — and Does Not — Establish
The primary PFS HR of 0.387 indicates a lower estimated hazard of progression or death with sacituzumab govitecan relative to TPC in the BM-ve analysis population.
The ClinicalTrials.gov record does not provide median PFS, time-specific PFS probabilities, or absolute numbers of PFS events by arm. Therefore, the primary HR should not be converted into an absolute months-of-benefit estimate.
The reported P-value of <0.0001 indicates strong statistical evidence against the null hypothesis represented by the reported log-rank test. It does not measure the magnitude of the treatment effect.
The 95% CI of 0.305–0.492 communicates uncertainty around the primary HR. The interval remains below 1, while still spanning a meaningful range of possible relative effects.
The primary estimate applies to the BM-ve population as defined in the registry. The separate ITT PFS analysis provides a different population-level estimate of 0.413.
18. Multiplicity, Interim Analysis, and Other Design Topics
The ClinicalTrials.gov record identifies the primary endpoint, secondary endpoints, methods, effect measures and analysis populations. They do not provide a prespecified multiplicity-adjustment strategy, interim-analysis schedule, alpha-spending plan, missing-data imputation method, crossover procedure, non-inferiority margin, factorial structure, or Bayesian analysis.
| Design topic | What the ClinicalTrials.gov record supports |
|---|---|
| Multiplicity | Not specified in the ClinicalTrials.gov record. |
| Interim analysis | Not specified in the ClinicalTrials.gov record. |
| Alpha spending | Not specified in the ClinicalTrials.gov record. |
| Missing-data / imputation | Not specified in the ClinicalTrials.gov record. |
| Non-inferiority margin | Not applicable to the reported hypothesis description; no non-inferiority margin is reported. |
| Crossover | Not specified in the ClinicalTrials.gov record. |
| Factorial design | Not present; the registered design model is parallel. |
| Bayesian methods | Not reported among the registry-reported statistical methods. |
| Stratification | The primary BM-ve population is explicitly defined by randomization strata with no baseline brain metastasis. |
This distinction is important. Absence of a method in the ClinicalTrials.gov recordset does not establish that a method was never used elsewhere in the trial's protocol or statistical analysis plan. It means only that the method is not supported by the ClinicalTrials.gov record.
19. Limitations
- Registry-level detail: the ClinicalTrials.gov record provides selected endpoint definitions and statistical analyses but do not provide the complete statistical analysis plan.
- Limited absolute outcome information: the posted analyses reported here include relative effect estimates and confidence intervals but do not provide the median survival or absolute response percentages needed for a fuller absolute-effect interpretation.
- Primary population: the primary PFS result applies to the BM-ve population rather than automatically to every randomized participant.
- Different estimands: PFS, OS, ORR, DOR, TTP and CBR measure different clinical phenomena and should not be interpreted as interchangeable endpoints.
- Responder-only DOR: DOR is analyzed among participants with objective response, so it is not an ITT treatment comparison from randomization.
- Assessment source: IRC and investigator analyses can produce different estimates, as seen in the registry-reported DOR and other secondary results.
- Hazard-ratio interpretation: a single HR summarizes relative time-to-event experience and should not automatically be interpreted as a constant relative risk at every time point.
- Safety detail: the ClinicalTrials.gov record contains serious adverse-event counts by arm but not the complete adverse-event profile.
- Unreported methods: multiplicity, interim monitoring, missing-data procedures and other advanced design features are not described in the ClinicalTrials.gov record.
20. Why This Trial Matters Statistically
ASCENT is a useful teaching case because it combines randomized treatment allocation with several distinct statistical estimands. The primary endpoint is a time-to-event outcome analyzed with a log-rank test and summarized using a hazard ratio, while secondary analyses extend the statistical framework to ITT survival outcomes, binary response endpoints, responder-only DOR, and progression endpoints assessed by different sources.
| Concept | How it appears in ASCENT |
|---|---|
| Randomization | Participants were randomized in a parallel-group phase 3 design. |
| ITT analysis | PFS and OS were separately analyzed in the ITT population. |
| BM-ve analysis population | The primary PFS endpoint was analyzed among randomized participants in strata with no baseline brain metastasis. |
| Time-to-event endpoints | PFS, OS, DOR and TTP were analyzed with survival-analysis methods. |
| Log-rank test | Used for the reported PFS, OS, DOR and TTP comparisons. |
| Hazard ratio | Used to quantify relative effects for time-to-event endpoints. |
| Cochran-Mantel-Haenszel test | Used for the reported ORR and CBR analyses. |
| Odds ratio | Used as the effect measure for binary ORR and CBR outcomes. |
| Confidence intervals | 95% two-sided intervals accompany the posted effect estimates. |
| Assessment source | IRC and investigator assessments are reported separately for several secondary endpoints. |
| Responder population | DOR analyses were restricted to BM-ve participants with objective response. |
| Safety denominator | Serious adverse events are reported as affected participants over participants at risk by arm. |
21. Related Tutorials
Learn more about the methods used in this trial:
22. Related Statistical Calculators
23. Sources
- ClinicalTrials.gov: ASCENT, NCT02574455.
- PubMed: PMID 40657894.
- PubMed: PMID 39324726.
- PubMed: PMID 38664404.
- PubMed: PMID 38422473.
- PubMed: PMID 35545724.
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24. Record Summary
ASCENT provides a detailed example of how a randomized phase 3 oncology trial can generate several related but distinct statistical questions. Its primary registered endpoint, PFS by IRC assessment in the BM-ve population, was analyzed with a log-rank test and produced an HR of 0.387 (95% CI 0.305–0.492; P < 0.0001). The registry also reports ITT PFS, BM-ve and ITT OS, ORR, DOR, TTP and CBR analyses using hazard ratios or odds ratios with two-sided 95% confidence intervals.
The most important statistical lesson is that these estimates should be interpreted according to their endpoint and analysis population. A hazard ratio describes a relative time-to-event effect; an odds ratio describes relative odds for a binary outcome; DOR applies only to responders; and the BM-ve primary analysis is distinct from the ITT analysis. Confidence intervals communicate precision, while P-values address statistical evidence rather than effect size.