Olaparib Treatment in Relapsed Germline Breast Cancer Susceptibility Gene (BRCA) Mutated Ovarian Cancer Patients Who Have Progressed at Least 6 Months After Last Platinum Treatment and Have Received at Least 2 Prior Platinum Treatments: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Olaparib Treatment in Relapsed Germline Breast Cancer Susceptibility Gene (BRCA) Mutated Ovarian Cancer Patients Who Have Progressed at Least 6 Months After Last Platinum Treatment and Have Received at Least 2 Prior Platinum Treatments (NCT02282020), a randomized phase 3 study. The primary outcome is Objective Response Rate (ORR).

2. Clinical Question

3. Trial Design

This was a Phase III, open-label, randomized, controlled, multicentre study comparing olaparib monotherapy with physician’s choice single-agent chemotherapy. The registry lists 266 participants as the enrollment and marks the study completed. The recorded start date is 2015-02-06, and the primary completion date is 2018-10-10. The official title identifies the trial as a comparison in platinum-sensitive relapsed ovarian cancer among patients carrying germline BRCA1/2 mutations.

The treatment arms were olaparib 300 mg oral tablets twice daily and physician’s choice single-agent chemotherapy. The study was open label, so masking is recorded as none. The registry does not identify the particular chemotherapy agents chosen or describe how that choice was made.

The primary outcome was objective response rate, assessed by blinded independent central review using RECIST 1.1. The primary analysis population was the Measurable Disease Analysis Set: Full Analysis Set participants with measurable disease at baseline, determined by the central review. The listed assessment schedule was every 8 weeks (±1 week) up to 48 weeks and then every 12 weeks (±1 week), with the primary outcome assessed to the 10Oct2018 data cut-off.

Secondary outcomes included progression-free survival, time to second progression, overall survival, response duration, and measures of time to subsequent therapy or treatment discontinuation. Several outcomes were assessed to a later data cut-off, 16Apr2021. The registry record does not report the original sample-size justification, detailed randomization procedures, or the trial’s complete statistical analysis plan.

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.

Before assignment: Participants were randomized in a 2:1 ratio between olaparib and single agent chemotherapy. Of the 266 patients randomised, 178 patients were in the olaparib arm and 88 in the chemotherapy arm.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: The Measurable Disease Analysis Set (MDAS) includes all participants in the Full Analysis Set (FAS) with measurable disease at baseline (as per RECIST 1.1), determined using Blinded Independent Central Review.

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: Baseline characteristics are displayed for all participants who started the study. This includes the 12 participants who did not receive treatment in the 'Single Agent Chemotherapy' arm.

6. Primary Endpoint

The registry lists the primary outcome as Objective Response Rate (ORR), measured over RECIST follow-up assessments performed every 8 weeks (±1 week), up to 48 weeks, then every 12 weeks (±1 week) from randomisation, assessed from date of first patient randomised to data cut off: 10Oct2018 (approx. 3 years 8 months).

The primary endpoint, objective response rate (ORR), is the count of participants with a complete response or partial response in the Measurable Disease Analysis Set. Response was evaluated using RECIST 1.1 by blinded independent central review. A complete response required disappearance of all lesions, with the stated nodal-disease criterion; a partial response required a decrease in the sum of target-lesion diameters of at least 30%.

ORR is used to describe whether measurable tumors meet prespecified criteria for shrinking or disappearing during assessment. It is a response endpoint, not a direct measure of how long participants live or how long disease control continues. The registry lists progression-free survival, second progression, overall survival, and other time-based outcomes separately, which address different aspects of the disease course.

The endpoint’s denominator is not all randomized participants: the registry defines the analysis set as Full Analysis Set participants who had measurable disease at baseline under central review. The posted counts are 109 responses among 151 participants in the olaparib arm and 37 among 72 in the chemotherapy arm. These are the counts used to characterize the primary response result; the registry’s reported sponsor analysis is a logistic-regression odds ratio, while the posted unadjusted recalculation expresses the contrast as a risk difference.

Blinded central assessment can reduce the influence of knowledge of assigned treatment on response classification, even though the overall study was open label. The registry does not report further details of the central-review procedures or how missing response assessments were handled.

7. Results Posted in the Registry

• Single Agent Chemotherapy: 51.4% (37/72) versus 72.2% (109/151) on control; risk difference -20.8 percentage points (95% CI -34.4 to -7.2), risk ratio 0.71 (0.56–0.91); unadjusted two-proportion z-test p = 0.002.

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.

Progression Free Survival (PFS)

• 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:
  • Olaparib 300 mg BID vs Single Agent Chemotherapy: hazard ratio 0.62 (95% CI 0.43–0.91), reported p = 0.013 (as reported in the registry).
• Interpretation:
  • The 95% confidence interval excludes no difference (a ratio of 1), so the hazard of the event is statistically lower for Olaparib 300 mg BID vs Single Agent Chemotherapy than for the control. This is an unadjusted, secondary comparison, so it is suggestive rather than confirmatory.

Time From Randomisation to Second Progression (PFS2)

• 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:
  • Olaparib 300 mg BID vs Single Agent Chemotherapy: hazard ratio 0.80 (95% CI 0.56–1.15), reported p = 0.229 (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 Olaparib 300 mg BID vs Single Agent Chemotherapy and the control. The interval gives the range of effects that remain compatible with the data.

Overall Survival (OS)

• 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:
  • Olaparib 300 mg BID vs Single Agent Chemotherapy: hazard ratio 1.07 (95% CI 0.76–1.49), reported p = 0.714 (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 Olaparib 300 mg BID vs Single Agent Chemotherapy and the control. The interval gives the range of effects that remain compatible with the data.

Across the posted secondary outcomes, the pattern is not uniform. The progression-free survival estimate favors olaparib by the reported hazard-ratio direction and its interval does not include the null value. The time-to-second-progression estimate points in the same direction, but its interval includes the null value. The overall-survival estimate is close to the null value and its interval also includes it. Thus, the secondary results provide differing levels of evidence and should not be reduced to a single claim about all outcomes.

Progression-free survival is related to the primary response result because both concern disease status, but they are not interchangeable endpoints. ORR records whether a participant met response criteria, whereas progression-free survival incorporates the time until the defined progression or death event. Second progression and overall survival address later or different points in the disease course. Agreement or disagreement across these outcomes can inform interpretation, but one endpoint does not validate or negate another by itself.

The secondary endpoints are numerous, and the registry lists 20 posted secondary outcomes. When many outcomes are examined, the chance of observing apparently notable results by chance can increase unless the analysis plan accounts for multiplicity. The registry record does not report a multiplicity adjustment strategy for these secondary comparisons. Their p-values and intervals should therefore be treated as less definitive than a prespecified primary result unless the full analysis plan establishes otherwise. The record also does not report enough detail to determine which secondary analyses were confirmatory or exploratory.

Follow-up and analysis populations differ across outcomes. Some results use the later 16Apr2021 data cut-off, while the primary result and progression-free survival use the 10Oct2018 cut-off. These distinctions affect how the outcomes can be compared and reinforce the need to read each result according to its endpoint definition and follow-up period.

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

• Progression Free Survival (PFS)
• Time From Randomisation to Second Progression (PFS2)
• Overall Survival (OS)
• Time To Earliest Progression By RECIST 1.1 Or Cancer Antigen (CA) -125 Or Death
• Time From Randomization To First Subsequent Therapy Or Death (TFST)
• Time From Randomization To Second Subsequent Therapy Or Death (TSST)
• Time From Randomization To Study Treatment Discontinuation Or Death (TDT)
• Duration of Response (DoR)

9. Statistical Interpretation

10. Statistical Methods Explained

The primary endpoint is a binary response outcome: each participant in the defined analysis set either met the criteria for complete or partial response or did not. The registry reports response counts and a sponsor analysis using logistic regression. It also posts an unadjusted recalculation expressed as a risk difference. These methods answer related but distinct questions, so their effect estimates use different scales.

What does the odds ratio describe?

An odds ratio compares the odds of response between treatment groups. An odds ratio of 1 corresponds to equal response odds under the modeled comparison; values on either side of 1 indicate a difference in the direction determined by group ordering. The sponsor reports an odds ratio of 2.53, a 95% confidence interval from 1.40 to 4.58, and p = 0.002. The registry identifies the method as logistic regression, but does not report the covariates, model specification, or other details needed to characterize the adjustment fully.

How is a risk difference different?

A risk difference subtracts one group’s response proportion from the other group’s response proportion. It is expressed on the probability scale and describes the absolute contrast rather than the ratio of odds. The posted unadjusted recalculation reports a risk difference of -0.208 for chemotherapy relative to olaparib, with an unadjusted p-value of 0.002. The sign depends on the order of the groups in the contrast. This is a simple calculation from the posted summary counts, not the sponsor’s regression model.

What does the p-value say?

A p-value describes how compatible the observed data are with a specified null hypothesis under the assumptions of the test. It is not the probability that the null hypothesis is true, nor does it describe the size or practical importance of an effect. The sponsor’s primary p-value is 0.002; the registry also reports 0.002 for the unadjusted recalculation. The registry record does not give the full details needed to reconstruct every aspect of the sponsor’s analysis.

How are time-to-event outcomes analyzed?

Progression-free survival, time to second progression, and overall survival are reported as medians with 95% confidence intervals and as hazard ratios from log-rank analyses. A median time is the point by which half of the analyzed group has experienced the event, under the time-to-event definition. A hazard ratio compares event rates over follow-up, subject to the assumptions of the method; it is not a ratio of median times. A value below 1 indicates a lower estimated event hazard for the numerator group under the reported ordering, while a value above 1 indicates a higher estimate. The registry reports the hazard ratios and intervals but does not report a proportional-hazards assessment.

The registry also includes planning illustrations based on observed effects. These are not the original trial design calculations. Their assumptions are described separately with the planning figures. The record does not report the trial’s original sample-size justification or interim-analysis plan, so neither should be inferred from the posted outcome analyses.

What do analysis populations contribute?

Different outcome measures can use different analysis sets. The primary ORR population is explicitly restricted to participants with measurable disease at baseline within the Full Analysis Set. The posted ORR denominators are 151 and 72. The time-to-event outcomes list 178 and 88 participants in their respective arms. Those denominators should not be substituted for the primary endpoint’s denominators. The registry does not provide a complete account of all analysis-set definitions or explain all differences in denominators.

Blinded independent central review was used to assess RECIST response, while the trial itself was open label. This separates the response assessment from the open-label treatment setting to some extent, but the registry record does not describe reviewer procedures, adjudication, or missing-assessment handling. These methodological details matter when judging how outcomes were defined and analyzed.

11. Confidence Intervals and Precision

A confidence interval gives a range of estimates compatible with the data and the method used to construct the interval. It communicates uncertainty around an estimate; it is not a range containing a fixed percentage of individual participant outcomes. A wider interval indicates less precision than a narrower interval, all else equal. An interval that includes the null value for its effect measure signals that the data are compatible with no difference under that interval procedure, although the interval alone does not capture every consideration relevant to interpretation.

For the sponsor’s primary logistic-regression analysis, the reported odds ratio is 2.53, with a 95% confidence interval from 1.40 to 4.58. The interval is entirely above 1, and the reported p-value is 0.002. The registry’s unadjusted risk-difference estimate is -0.208; its interval is reported in the recalculation, but is not repeated because the registry’s bounds have more than 3 decimal places.

For progression-free survival, the reported hazard ratio is 0.62 with a 95% confidence interval from 0.43 to 0.91. For time to second progression, the estimate is 0.80 with a 95% confidence interval from 0.56 to 1.15. For overall survival, the estimate is 1.07 with a 95% confidence interval from 0.76 to 1.49. The latter two intervals include 1, indicating that their estimates are less conclusive about a difference than the progression-free survival interval. These comparisons should be read alongside the different follow-up periods and analysis populations.

Precision depends on the amount and distribution of outcome information, not simply on the point estimate. Confidence intervals also rely on the assumptions of their statistical methods. The registry record does not report all model diagnostics, missing-data procedures, or analysis-plan details needed to assess those assumptions fully.

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 are illustrations derived from the observed effect, not the trial’s original design calculation. For the binary response outcome, figures are participants per arm. For time-to-event outcomes, figures are total events, not participants per arm. The planning assumptions are a two-sided significance level of 0.05, equal allocation between the two arms, and a normal approximation; each illustration uses the stated fraction of the observed effect as the effect to detect. The original trial design assumptions are not reported in the registry record.

The 80% power column describes the illustrated number of participants per arm, or total events for a time-to-event outcome, under which the specified design would have an 80% chance of detecting the assumed effect at the stated significance level. The 90% column uses a higher probability of detection under those same planning conditions. These are planning concepts, not guarantees: actual power depends on the true effect, event or response information, and whether the assumptions hold.

The illustrations show planning for 100%, 75%, and 50% of the observed effect. Smaller effects need more participants or events to detect with the same target power. For the primary response comparison, the planning figures are per arm; for progression-free survival, second progression, and overall survival, they are total events. Those different units must not be compared as if they represented the same quantity.

This is not observed power. The illustrations are hypothetical planning calculations based on the observed effects and are not evidence that the completed trial had a particular probability of detecting its results.

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

n is the number of participants in each arm, p₀ and p₁ are the control and treatment proportions, and p̄ is their average.

Worked calculation for this trial

1. Control proportion p₀ = 0.722; treatment proportion p₁ = 0.514; average p̄ = 0.618.
2. First term: z_1−α/2 × √[2p̄(1−p̄)] = 1.96 × 0.6872 = 1.3468.
3. Second term: z_1−β × √[p₀(1−p₀) + p₁(1−p₁)] = 0.842 × 0.6713 = 0.5649.
4. n = (1.3468 + 0.5649)² / (-0.2080)² = 84.5, rounded up to 85 participants per arm 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
p0 <- 0.721854304635762                          # control proportion
p1 <- 0.513888888888889                          # treatment proportion
n_per_arm <- function(power, frac = 1) {
  q1 <- p0 + (p1 - p0) * frac               # smaller effect = fraction of the observed difference
  pbar <- (p0 + q1) / 2
  z_b <- qnorm(power)
  ceiling(round((z_a * sqrt(2 * pbar * (1 - pbar)) + z_b * sqrt(p0 * (1 - p0) + q1 * (1 - q1)))^2 / (q1 - p0)^2, 6))
}
for (f in c(1, 0.75, 0.5))
  cat(sprintf("%3.0f%% of observed effect: n per arm = %s (80%% power), %s (90%% power)\n", 100 * f,
              format(n_per_arm(0.80, f), big.mark = ","), format(n_per_arm(0.90, f), big.mark = ",")))

# Check against R's built-in function (unrounded n per arm)
cat("power.prop.test:", round(power.prop.test(p1 = p0, p2 = p1, power = 0.80)$n, 1), "\n")

# Simulation: how often does the z-test reject at the 80%-power sample size?
set.seed(2282020)
n    <- n_per_arm(0.80)
reps <- 20000
x0 <- rbinom(reps, n, p0); x1 <- rbinom(reps, n, p1)
ph <- (x0 + x1) / (2 * n)
z  <- ((x1 - x0) / n) / sqrt(ph * (1 - ph) * 2 / n)
cat(sprintf("Simulated power at n = %s per arm: %.3f (%d replicates)\n", format(n, big.mark = ","), mean(abs(z) > z_a, na.rm = TRUE), reps))

Output from running the code

100% of observed effect: n per arm = 85 (80% power), 113 (90% power)
 75% of observed effect: n per arm = 147 (80% power), 196 (90% power)
 50% of observed effect: n per arm = 320 (80% power), 428 (90% power)
power.prop.test: 84.5 
Simulated power at n = 85 per arm: 0.802 (20000 replicates)

The simulation draws many pairs of event counts at the planned sample size and counts how often the two-proportion z-test rejects the null. It should land close to the target power; at very small required sample sizes it can fall below it, because the normal approximation is rough there.

14. Analyses Reported by the Sponsor

The registry reports the sponsor’s primary analysis as logistic regression, with an odds ratio of 2.53, a 95% confidence interval from 1.40 to 4.58, and p = 0.002. The unadjusted recalculation instead reports a risk difference of -0.208 and p = 0.002. The odds ratio and risk difference use different scales and, in the recalculation, the group contrast is expressed in the opposite direction. Their numerical values should not be compared as if they were estimates of the same quantity.

The sponsor’s analysis is the trial’s reported analysis and is the primary reference for interpreting the sponsor result. The registry does not flag a discrepancy between that result and the recalculation. The recalculation is a simple, unadjusted analysis from the posted response counts; it does not reproduce the logistic-regression model. The regression covariates and full model specification are not reported in the registry record, so the distinction between any adjusted and unadjusted aspects cannot be examined further.

Both analyses concern ORR in the Measurable Disease Analysis Set, but the sponsor’s model and the unadjusted contrast answer the question in different statistical terms. The sponsor result should therefore be read as the reported model-based result, while the recalculation serves as a transparent descriptive contrast from the posted counts rather than a replacement for the sponsor analysis.

15. Multiplicity, Missing Data and Analysis Populations

Multiplicity arises when a study evaluates several outcomes, comparisons, or analysis choices. Even if each individual test uses a prespecified threshold, repeated testing can increase the chance of at least one apparently significant result when no true effect exists. A multiplicity strategy may define a hierarchy, allocate error rates across outcomes, or identify analyses as exploratory. The registry lists numerous secondary outcomes and 20 posted secondary outcomes, but a multiplicity adjustment or testing hierarchy is not reported in the registry record. Accordingly, secondary p-values should not automatically be interpreted with the same confirmatory force as the primary result.

The record identifies the primary ORR analysis population and the central-review response definition. It also reports analysis denominators that differ across the primary and time-to-event outcomes. However, detailed handling of missing response assessments, censoring, protocol deviations, treatment discontinuation, and participants excluded from particular analyses is not reported in the registry record. Without those details, the impact of missing or incomplete observations cannot be assessed from the posted results alone.

The registry also does not report the original sample-size justification, assumptions for the study’s own design, planned interim analyses, or a complete statistical analysis plan. The planning illustrations based on observed effects are separate from those design decisions and cannot fill in the missing protocol details. The logistic-regression method is named for the primary sponsor analysis, but covariates and full model specification are not reported.

These omissions do not erase the recorded estimates, but they limit independent assessment of how analyses were prespecified and implemented. A complete interpretation would distinguish the primary endpoint from secondary analyses, account for any multiplicity control, and evaluate the treatment of missing data under the analysis plan. Those details are not available in the registry record.

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: vomiting (3.9%), anaemia (3.4%), pyrexia (2.6%), pleural effusion (2.6%), nausea (2.6%).

The registry reports serious adverse events for safety groups with 178 participants at risk in the olaparib group and 76 in the single-agent chemotherapy group. It records 46 participants with serious adverse events in the olaparib group and 14 in the chemotherapy group. These are counts from the safety reporting populations, which differ from the primary ORR denominators. They should be read as serious adverse event counts in the stated groups, not as direct comparisons of response outcomes.

The registry lists vomiting at 3.9%, anaemia at 3.4%, pyrexia at 2.6%, pleural effusion at 2.6%, nausea at 2.6%, and deep vein thrombosis at 1.7% among the top serious adverse event terms. It also records other adverse events affecting 173 of 178 participants in the olaparib safety group and 73 of 76 in the chemotherapy group, and deaths of 116 and 46, respectively. These figures do not by themselves establish whether an event was caused by treatment or explain its timing, duration, or clinical course.

The registry record does not provide enough detail to assess comparative safety comprehensively, including full event definitions, exposure-adjusted analyses, or event-level attribution. Counts should be interpreted in the context of the safety population and the reporting information available.

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

The primary result describes a higher observed response proportion in the olaparib arm than in the physician’s choice chemotherapy arm within the Measurable Disease Analysis Set. The sponsor’s logistic-regression result and the posted unadjusted recalculation both report p = 0.002, while expressing the contrast on different scales. The estimate and its interval characterize the size and uncertainty of the comparison; the p-value alone does not describe clinical importance or the probability that a treatment effect is true.

The result applies to the trial population and the response endpoint as defined: participants with measurable disease at baseline, with response assessed by blinded independent central review under RECIST 1.1. It does not directly answer how long a response lasted, how long participants remained progression-free, or whether overall survival differed. Those questions are addressed by separate secondary outcomes with their own follow-up and uncertainty.

The findings also do not mean that every participant responded, that every person with the condition would have the same outcome, or that the comparison applies to treatments and populations outside those recorded. The chemotherapy comparator was physician’s choice, and the specific agents are not reported in the registry record. The study was open label, although primary response was assessed by blinded independent central review.

Statistical evidence should be read with the confidence interval, analysis population, endpoint definition, and study design. Secondary outcomes are numerous and their multiplicity handling is not reported. Missing-data procedures and the original design assumptions are also not reported in the registry record. These limits matter when judging how much weight to place on the full set of results.

The registry findings are a statistical description of this randomized comparison, not medical advice and not a guarantee of an individual outcome. They support interpretation of the reported estimates within the study’s scope, while leaving questions about generalizability, detailed analysis choices, and the complete safety profile unresolved by the registry entry.

18. Why This Trial Matters Statistically

This trial illustrates why an endpoint’s definition and analysis population matter. The primary outcome is not a count across every randomized participant; it is a response count within the measurable-disease analysis set. The denominators for the primary result differ from those listed for time-to-event outcomes, so a single enrollment figure cannot stand in for every endpoint’s analyzed population.

It also shows why effect measures should be distinguished. The sponsor reports a logistic-regression odds ratio, whereas the unadjusted recalculation uses a risk difference. Both describe the primary response contrast, but they use different scales and group ordering. A reader who treats their numerical values as interchangeable could misstate the result.

The time-to-event outcomes add a separate perspective: estimates, intervals, and p-values do not all convey the same degree of certainty. Considering those results alongside the primary response endpoint helps keep response, progression, and survival questions distinct. The later data cut-off for some secondary outcomes further demonstrates why follow-up timing is part of interpretation.

Finally, the registry record leaves key design and analysis details unreported, including the original sample-size justification, multiplicity strategy, and detailed missing-data methods. Recognizing these gaps is part of sound statistical reading. The posted estimates can be described clearly without treating unreported procedures as known or allowing planning illustrations to be mistaken for the trial’s original design.

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 limitations are specific to the information available for this trial. The study was open label, although the primary response assessment used blinded independent central review. The registry record does not describe the central-review process in detail, including adjudication procedures or how disagreements were handled. It also does not report the specific chemotherapy agents selected under physician’s choice, limiting description of the comparator beyond its single-agent category.

The primary endpoint was assessed in the Measurable Disease Analysis Set rather than all randomized participants. The registry defines that set, but detailed counts and reasons for exclusion from it are not reported beyond the posted denominators. The analysis populations for secondary outcomes have different denominators, and the record does not fully explain those differences. Missing response data, censoring rules, and sensitivity analyses are not described in sufficient detail to assess their effect.

The sponsor’s logistic-regression analysis is identified by method, but the covariates and model specification are not reported. The record also does not report the complete analysis plan, multiplicity control for the numerous secondary outcomes, original sample-size rationale, or interim-analysis plan. These gaps restrict independent evaluation of prespecification and robustness.

Follow-up cut-offs differ between the primary outcome and some later secondary outcomes, so those estimates reflect different periods of observation. The safety figures are counts in safety groups, but detailed exposure-adjusted comparisons and event attribution are not reported. As with any registry entry, the available record supports interpretation of the posted results but cannot answer questions for which methods or results are absent.

20. Related Tutorials

21. Related Statistical Calculators

22. Sources

• ClinicalTrials.gov: Olaparib Treatment in Relapsed Germline Breast Cancer Susceptibility Gene (BRCA) Mutated Ovarian Cancer Patients Who Have Progressed at Least 6 Months After Last Platinum Treatment and Have Received at Least 2 Prior Platinum Treatments — NCT02282020.
• Registry record last updated 2022-07-26; status last verified 2022-07.
• Results first posted 2019-12-02.
• 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

NCT02282020 is a completed, randomized, open-label, controlled Phase III study of olaparib versus physician’s choice single-agent chemotherapy in platinum-sensitive relapsed ovarian cancer with germline BRCA1/2 mutations. The registry lists enrollment of 266 participants. The primary endpoint was objective response rate assessed by blinded independent central review in participants with measurable disease at baseline.

The posted primary result records 109 responses among 151 participants in the olaparib arm and 37 among 72 in the chemotherapy arm. The sponsor reports a logistic-regression odds ratio of 2.53, with a 95% confidence interval from 1.40 to 4.58 and p = 0.002. Secondary outcomes include progression-free survival, time to second progression, overall survival, and other disease-course and treatment measures.

The registry record does not report the original sample-size justification, full multiplicity strategy, detailed missing-data procedures, or complete statistical analysis plan. The results should be interpreted within their stated endpoint definitions, populations, and follow-up periods.