Rucaparib in Treating Patients With Genomic LOH High and/or Deleterious BRCA1/2 Mutation Stage IV or Recurrent Non-small Cell Lung Cancer (A Lung-MAP Treatment Trial): Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Rucaparib in Treating Patients With Genomic LOH High and/or Deleterious BRCA1/2 Mutation Stage IV or Recurrent Non-small Cell Lung Cancer (A Lung-MAP Treatment Trial) (NCT03845296), a na phase 2 study. The primary outcome is Overall Response Rate.

2. Clinical Question

The study focused on a biologically selected group: participants had genomic LOH high and/or a deleterious BRCA1/2 mutation, as well as stage IV or recurrent non-small cell lung cancer. The registry record frames the study as an evaluation of rucaparib in this population. It does not report a comparison with another treatment or with an untreated group, so the primary question is about the response observed among participants receiving the study drug, not a relative treatment effect against a control.

The response definition includes complete and partial responses, whether confirmed or unconfirmed. Complete response requires disappearance of target and non-target lesions, no new lesions, no disease-related symptoms, and a specified reduction in lymph-node short axis. Partial response requires a measurable lesion and a decrease in the sum of target-lesion diameters, with no unequivocal progression of non-measurable disease and no new lesions. The registry record also specifies that disease assessments use the same technique as at baseline.

3. Trial Design

This was a phase II, single-group study in the LUNG-MAP treatment trial program, sponsored by SWOG Cancer Research Network. The registry lists enrollment as 64 and the study status as completed. The recorded start date is 2019-04-16, and the primary completion date is 2022-01-01. These dates describe the registry record; they do not supply an outcome result.

Participants received rucaparib by mouth twice daily on days 1-21, with courses repeating every 21 days in the absence of disease progression or unacceptable toxicity. The registry lists no masking. Allocation is recorded as not applicable, consistent with the single-group model. There is no randomized control arm, and outcomes cannot be interpreted as a direct comparison between rucaparib and another treatment within this study.

The primary outcome is overall response rate, defined as the percentage of eligible and evaluable participants with a complete or partial response, confirmed or unconfirmed. The assessment window runs from registration to a maximum of 3 years or death. The listed secondary outcomes are investigator-assessed progression-free survival, overall survival, duration of response, and the number of participants with grade 3 through 5 adverse events related to study drugs.

The registry record does not report the study's sample-size justification, detailed statistical analysis plan, eligibility criteria, or operational details of response assessment beyond the endpoint definition. It also does not report the primary response estimate or confidence interval. The absence of a control group is important when interpreting any response proportion: it describes outcomes among treated participants but does not by itself estimate what would have happened under another treatment or without study treatment.

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: 64 participants were initially enrolled. Three participants were ineligible, one was not analyzable and one withdrew consent prior to starting the study drug. In all, 59 participants were eligible and included in the analysis: 25 in the squamous cohort and 34 in the non-squamous cohort.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: Eligible and evaluable participants

5. Baseline Characteristics

The table reproduces the baseline characteristics posted in the registry, which describe the participants analysed at baseline and help show whether the randomized groups were comparable.

Population: Eligible and evaluable participants

6. Primary Endpoint

The registry lists the primary outcome as Overall Response Rate, measured over From date of registration to a maximum of 3 years or death.

The primary endpoint, overall response rate, is the percentage of eligible and evaluable participants who had a complete or partial response. The registry allows responses to be confirmed or unconfirmed and specifies an assessment period from registration through a maximum of 3 years or death. Complete response and partial response are based on changes in lesions and the appearance of new lesions, with assessment techniques kept consistent with baseline.

A response proportion is a binary-outcome summary: each participant contributes according to whether the response definition was met. It offers a direct description of how many participants experienced tumor shrinkage meeting the stated criteria, but it does not describe how long a response lasted. Duration of response is listed separately as a secondary outcome. Nor does response rate alone describe disease progression, survival, or adverse effects; those are addressed by separate listed outcomes.

General statistical context: a confidence interval communicates uncertainty around an estimated response proportion. A narrower interval indicates greater precision under the method used, while a wider interval indicates more uncertainty. The registry identifies a 95% confidence interval as the endpoint's dispersion measure, but the response estimate and interval are not reported in the registry record. Therefore, the observed response proportion and its precision cannot be assessed from the registry information.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry identifies overall response rate as a percentage and a 95% confidence interval as its dispersion measure. It defines the primary population as eligible and evaluable participants. The response event is a complete or partial response, whether confirmed or unconfirmed, assessed from registration to a maximum of 3 years or death. These details identify the type of outcome and the intended summary, but not the calculation method, evaluability rules, or handling of participants without an assessable response. Those analysis details are not reported in the registry record.

What a response percentage represents

General statistical context: a percentage for a binary outcome is based on the number of participants meeting the event definition relative to the population used in the analysis. The definition of that population is consequential. If participants who cannot be assessed are excluded, the resulting percentage describes the evaluable group rather than necessarily everyone enrolled. The registry names an eligible and evaluable population, but it does not report the number of participants in that population or the rules used to classify participants as evaluable. No response percentage can be reconstructed from the registry information.

The outcome definition also combines several response categories. Complete response requires complete disappearance of target and non-target lesions, absence of new lesions and disease-related symptoms, and reduction of lymph nodes to the specified short-axis criterion. Partial response requires at least one measurable lesion and a decrease of at least 30% from baseline in the sum of appropriate diameters of target measurable lesions, without unequivocal progression of non-measurable disease or new lesions. The registry states that assessments use the same technique as baseline. These rules describe the event being counted; they do not reveal how many participants met it.

How to understand the confidence interval

General statistical context: a confidence interval is an uncertainty summary around an estimate. It reflects sampling variability under the statistical procedure used; it is not a guarantee that the true value lies within the particular interval, and it does not correct for bias in study conduct or analysis. The registry specifies a 95% confidence interval for the primary outcome, but does not identify the interval method or report its limits. Consequently, precision cannot be evaluated.

For a percentage outcome, precision is influenced by the number of participants included in the analysis and by the distribution of outcomes. The enrollment entry alone is insufficient to determine the endpoint's precision because the primary population is eligible and evaluable participants, not simply the enrollment total. No denominator or event count is reported for the primary outcome.

What the design permits

General statistical context: a single-group study can describe outcomes among treated participants, but without a concurrent control group it does not estimate a between-group contrast. A response percentage is therefore not a randomized estimate of the difference attributable to treatment. The registry describes a single-group model, no masking, and allocation as not applicable; no randomized comparator is listed.

The sample-size planning information describes illustrations based on the observed effect, not the trial's own design. The stated illustration assumptions are a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation, with the effect to detect set as a stated fraction of the observed effect. These are planning assumptions for hypothetical comparisons, not evidence that the trial randomized participants between two arms. The original study's sample-size justification is not reported in the registry record. Such planning numbers should not be interpreted as observed power or as a result of the trial.

Multiple outcomes and analysis choices

The registry lists a primary response endpoint and secondary outcomes covering investigator-assessed progression-free survival, overall survival, duration of response, and grade 3 through 5 adverse events related to study drugs. The detailed statistical analysis plan, including any multiplicity strategy, is not reported in the registry record. General statistical context: when several outcomes or analyses are examined, the chance of at least one apparently notable finding can increase if no adjustment or hierarchy is used. The registry's outcome list alone does not establish whether or how this issue was addressed.

The registry records zero analyses. It does not provide analysis populations beyond the primary endpoint's eligible and evaluable description, nor does it report missing-data procedures, censoring rules for time-to-event outcomes, or sensitivity analyses. General statistical context: these methods can affect estimates when some outcomes are unavailable or follow-up ends before an event. Their absence from the registry record means the treatment of those situations cannot be assessed from the information recorded.

10. Exact Estimates for Each Arm

No two-arm comparison is shown for this trial, but each arm's result can still be summarized with exact interval estimates computed from the posted counts. The Clopper-Pearson interval is exact and conservative; the Wilson interval is a common closer-to-nominal alternative; the Bayesian credible interval uses a uniform Beta(1, 1) prior. For small groups the three can differ noticeably.

R code and output

arm    <- c("Cohort 1: Squamous", "Cohort 2: Non-Squamous")
n      <- c(25, 34)
events <- c(2, 4)
for (i in seq_along(n)) {
  ci <- binom.test(events[i], n[i])$conf.int          # Clopper-Pearson exact interval
  cr <- qbeta(c(0.025, 0.975), 1 + events[i], 1 + n[i] - events[i])   # Bayesian, uniform Beta(1,1) prior
  wi <- (function(x, n) { p <- x / n; z <- qnorm(0.975); d <- 1 + z^2 / n
    c((p + z^2 / (2 * n) - z * sqrt(p * (1 - p) / n + z^2 / (4 * n^2))) / d, (p + z^2 / (2 * n) + z * sqrt(p * (1 - p) / n + z^2 / (4 * n^2))) / d) })(events[i], n[i])
  cat(sprintf("ARM|%s|%d|%d|%.1f|%.1f|%.1f|%.1f|%.1f|%.1f|%.1f\n", arm[i], n[i], events[i], 100 * events[i] / n[i],
              100 * ci[1], 100 * ci[2], 100 * wi[1], 100 * wi[2], 100 * cr[1], 100 * cr[2]))
}

ARM  Cohort 1: Squamous  25  2  8.0  1.0  26.0  2.2  25.0  2.4  25.1
ARM  Cohort 2: Non-Squamous  34  4  11.8  3.3  27.5  4.7  26.6  4.8  26.7

11. Multiplicity, Missing Data and Analysis Populations

The registry identifies overall response rate as the primary outcome and lists four secondary outcomes: investigator-assessed progression-free survival, overall survival, duration of response, and the number of participants with grade 3 through 5 adverse events related to study drugs. It records five outcome measures and zero analyses. It does not report whether a hierarchy among outcomes was used, whether statistical testing was planned, or whether any adjustment for multiple comparisons was specified. A multiplicity strategy is not reported in the registry record.

General statistical context: examining several outcomes can create more opportunities for chance findings, particularly when multiple significance tests are conducted. Prespecifying a primary endpoint can help distinguish the main question from supportive or exploratory questions, but the registry record's designation of a primary outcome does not reveal the full testing plan. Without an analysis plan or analysis entries, the statistical handling of the outcome family cannot be determined.

The primary population is described as eligible and evaluable participants, but the criteria for evaluability and the number analyzed are not reported in the registry record. The registry does not describe how missing response assessments, withdrawals, or other unavailable outcome data were handled. It also does not report the definition of analysis populations for the secondary outcomes. These omissions limit interpretation because the analyzed population and missing-data approach can affect the estimate and its precision.

General statistical context: missing outcomes may be handled in different ways, and each approach rests on assumptions about why data are missing. Without the study's rules and the amount of missing information, it is not possible to judge whether the analysis could be affected by missingness. For time-to-event outcomes, censoring and follow-up rules are also important, but they are not reported in the registry record. The listed outcomes therefore identify topics the study intended to assess without establishing how those assessments were analyzed.

12. 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: anemia (18.6%), dyspnea (11.9%), lung infection (8.5%), disease progression (6.8%), respiratory failure (6.8%).

The registry adverse-event summary lists 59 participants at risk for serious events, with 32 affected, and 59 at risk for other events, with 57 affected. These are counts in the adverse-event summary; they should not be confused with the primary response population or with the enrollment figure. The summary also lists 50 deaths. The timing, cause, and relationship to study treatment for those deaths are not reported in the registry record.

The serious-event terms listed with percentages are anemia, 18.6%; dyspnea, 11.9%; lung infection, 8.5%; disease progression, 6.8%; respiratory failure, 6.8%; and generalized muscle weakness, 5.1%. These percentages describe the listed terms in the adverse-event summary. The record does not provide further detail about overlap between terms, event duration, or attribution for each term.

The secondary outcome concerning grade 3 through 5 adverse events related to study drugs is distinct from the adverse-event summary counts. The number meeting that specific definition is not reported in the registry record. General statistical context: serious events and high-grade events are not interchangeable categories, and an event's seriousness does not by itself establish that the study drug caused it. The registry figures should therefore be read as descriptive safety information, not as proof of causation or as a comparison with another treatment.

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

The registry record describes a phase II study of rucaparib in participants with stage IV or recurrent non-small cell lung cancer selected for genomic LOH high and/or deleterious BRCA1/2 mutation. Its stated primary outcome is overall response rate among eligible and evaluable participants, with responses defined as complete or partial and confirmed or unconfirmed. However, the response estimate and 95% confidence interval are not reported in the registry record. The record therefore does not allow the primary outcome's observed magnitude or precision to be assessed.

The single-group design means the study's primary question is descriptive: what response proportion was observed among the analyzed participants receiving rucaparib? It is not a randomized estimate of a difference from another treatment. General statistical context: without a concurrent control group, differences between observed outcomes and outcomes under an alternative cannot be isolated using this design alone. The registry does not report a comparator arm.

The listed secondary outcomes cover progression-free survival, overall survival, duration of response, and treatment-related grade 3 through 5 adverse events. Their results are not reported in the registry record. The adverse-event summary does list serious and other event counts, selected serious-event terms and percentages, and a death count, but it does not establish causation or supply a treatment comparison. The specific number meeting the related grade 3 through 5 endpoint is not reported.

Accordingly, the registry information supports a description of the study's question, treatment schedule, design, and planned outcomes, but not a conclusion about the observed response result. General statistical context: even a precise estimate from a single-group study would describe the analyzed group under the study conditions; precision would not resolve the absence of a randomized comparator or possible limits in generalizability. The population is selected by disease stage or recurrence and genomic characteristics, so the findings, if reported, would pertain to that defined study population rather than automatically to all people with non-small cell lung cancer.

14. Why This Trial Matters Statistically

This trial illustrates how a clinical question, a population definition, and an endpoint definition work together. The study targets participants with stage IV or recurrent non-small cell lung cancer and genomic LOH high and/or deleterious BRCA1/2 mutation. Its primary outcome counts complete or partial responses, including confirmed or unconfirmed responses, in an eligible and evaluable population. Those definitions determine what a response percentage would mean and whom it would describe.

It also shows why a design description is not enough to interpret an efficacy estimate. The study is single-group, with no masking and no concurrent comparator. General statistical context: a single-group response proportion can describe observed outcomes, but a comparison of treatment effects requires a suitable reference group or another defensible design. The registry record does not report a randomized comparison, so the primary endpoint is not a relative treatment effect.

Precision is another essential part of interpretation. The registry specifies a 95% confidence interval, but does not report the response estimate, interval, or evaluable denominator. Without them, neither the level of response nor its uncertainty can be judged. Enrollment is recorded as 64, but the registry identifies eligible and evaluable participants as the primary analysis population; the number in that population is not reported.

The record also distinguishes the primary outcome from secondary outcomes and safety summaries. Progression-free survival, overall survival, duration of response, and treatment-related grade 3 through 5 adverse events address different questions. Their results and the detailed analysis plan are not reported in the registry record. Taken together, these features underscore a central statistical point: a clearly named endpoint and design provide a framework for interpretation, but outcome estimates and analysis details are needed to evaluate what was observed and how precisely it was measured.

15. 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 primary limitation for interpretation is that the registry record does not report the overall response rate or its 95% confidence interval. The number of eligible and evaluable participants, response counts, and results for the secondary outcomes are also not reported. Thus the registry description identifies what was intended to be measured but does not allow an assessment of the observed efficacy outcomes.

The single-group design has no concurrent comparator. Any reported response proportion would describe outcomes among participants receiving rucaparib under the study conditions, not a randomized contrast against another treatment. The registry lists no masking and allocation as not applicable. The record does not report the detailed analysis plan, sample-size justification, multiplicity approach, missing-data rules, or criteria for evaluability.

The safety information requires separate caution. The adverse-event summary reports affected-participant counts, selected serious-event terms and percentages, and a death count, but does not report the cause or treatment attribution for deaths. The specific count for the secondary outcome of related grade 3 through 5 adverse events is not reported in the registry record. The summary should not be treated as a causal comparison.

General statistical context: estimates from selected populations may not generalize to people outside the eligibility criteria, and study design cannot eliminate all sources of uncertainty. The registry record describes genomic and disease-stage selection but does not provide enough detail to assess recruitment, follow-up completeness, or the representativeness of enrolled participants. These matters remain unresolved in the registry information.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Rucaparib in Treating Patients With Genomic LOH High and/or Deleterious BRCA1/2 Mutation Stage IV or Recurrent Non-small Cell Lung Cancer (A Lung-MAP Treatment Trial) — NCT03845296.
• Registry record last updated 2025-05-21; status last verified 2025-05.
• Results first posted 2022-10-19.
• 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.

19. Record Summary

The registry record describes a completed phase II, single-group LUNG-MAP study sponsored by SWOG Cancer Research Network. It records enrollment of 64, a start date of 2019-04-16, and a primary completion date of 2022-01-01. Participants with stage IV or recurrent non-small cell lung cancer and genomic LOH high and/or deleterious BRCA1/2 mutation received rucaparib by mouth twice daily on days 1-21, with courses repeating every 21 days unless disease progressed or toxicity was unacceptable.

The primary endpoint was overall response rate among eligible and evaluable participants, with complete or partial responses, confirmed or unconfirmed, assessed through a maximum of 3 years or death. The response estimate and confidence interval are not reported in the registry record. Secondary outcomes included progression-free survival, overall survival, duration of response, and related grade 3 through 5 adverse events. The record lists adverse-event counts and selected serious-event terms, but not the detailed statistical analysis plan or the results for the listed outcomes.