A Study of IMC-A12 (Cixutumumab) With and Without Other Standard Chemotherapies in Participants With Lung Cancer Who Have Not Received Chemotherapy Before: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for A Study of IMC-A12 (Cixutumumab) With and Without Other Standard Chemotherapies in Participants With Lung Cancer Who Have Not Received Chemotherapy Before (NCT00870870), a randomized phase 2 study. The primary outcome is Percentage of Participants With Complete Response (CR) or Partial Response (PR) [Objective Response Rate (ORR)].

2. Clinical Question

The study was designed to examine objective response, meaning a measured reduction or disappearance of cancer lesions under the stated response criteria. The response outcome is a proportion, not a measure of how long a response lasted or how long participants lived without progression. Those topics appear among the secondary outcomes, but the registry record does not include posted numerical results for them in this record.

The treatment comparison is specifically the addition of cixutumumab to the gemcitabine, cisplatin and cetuximab regimen in the amended treatment groups. It is not a comparison of cixutumumab against no chemotherapy, and the efficacy summaries do not compare the original carboplatin-based groups. This distinction matters when interpreting both the clinical question and the available response estimates.

3. Trial Design

NCT00870870 is recorded as a completed phase 2, randomized, open-label, parallel-group study sponsored by Eli Lilly and Company. The listed condition is non-small cell lung cancer. The registry gives a start month of 2009-03 and a primary completion month of 2012-04. Enrollment is recorded as 64. The registry record does not report the original sample-size justification or the assumptions used to plan the trial.

The official title describes a randomized, open-label, stratified phase 2 comparison of gemcitabine, carboplatin and cetuximab with or without IMC-A12 in chemotherapy-naive participants with advanced or metastatic non-small cell lung cancer. The arm descriptions also state that cisplatin replaced carboplatin. The primary efficacy results concern the amended gemcitabine, cisplatin and cetuximab groups, with or without cixutumumab. Efficacy summaries were not reported for the original carboplatin-based groups because, under the amended protocol, those summaries were not considered relevant to the study objectives.

The control group for the primary comparison was gemcitabine, cisplatin and cetuximab alone. Its reported denominator was 29. The group receiving the same regimen plus cixutumumab had a reported denominator of 25. These are the denominators associated with the posted response results; the registry record does not explain how they relate to the enrollment field or give further accounting of participants by analysis status.

The study is described as open label, meaning masking was not used for the treatment assignment. Random allocation can help balance participant characteristics across groups, but the registry record does not report the allocation method, stratification factors, concealment procedures or protocol details beyond the stated design. It also does not report the trial’s own statistical analysis plan, planned interim analyses or original power assumptions. Those details should not be inferred from the posted effect estimates or the separate planning illustrations.

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

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: All participants randomized to GCiC and GCiC Plus Cixutumumab arms. Efficacy data were not summarized for the original treatment arms (GCC and GCC Plus Cixutumumab) since such summaries were not considered relevant to the study objectives under the amended protocol.

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: All randomized participants.

6. Primary Endpoint

The registry lists the primary outcome as Percentage of Participants With Complete Response (CR) or Partial Response (PR) [Objective Response Rate (ORR)], measured over Randomization to measured progressive disease (PD) (up to 16.9 months).

The primary endpoint was the percentage of participants who achieved either a complete response or a partial response, also called the objective response rate. A complete response meant disappearance of all target and non-target lesions and normalization of the tumor marker level. A partial response meant at least a 30% decrease in the sum of the longest diameters of target lesions, using the baseline sum as the reference. Response was defined by RECIST version 1.0.

The percentage was calculated using the number of participants with a complete or partial response divided by the number treated in the relevant group, multiplied by 100. The registry gives a timeframe from randomization to measured progressive disease, up to 16.9 months. This is a tumor-response endpoint: it captures whether participants met the specified response criteria during assessment, rather than the duration of response, time to progression, progression-free survival or overall survival.

Objective response is used in trials because it gives a defined way to summarize tumor shrinkage or disappearance across participants. It is a proportion, so the estimate depends both on the number meeting the criteria and on the group denominator. Its clinical interpretation is limited to the response definition and assessment period. The registry record does not provide further details about assessment schedules, independent review or handling of unevaluable participants.

7. Results Posted in the Registry

• GCiC Plus Cixutumumab: 20.0% (5/25) versus 31.0% (9/29) on control; risk difference -11.0 percentage points (95% CI -34.0 to 12.0), risk ratio 0.64 (0.25–1.67); unadjusted two-proportion z-test p = 0.356.

8. Statistical Interpretation

9. Statistical Methods Explained

What does the response percentage represent?

The primary outcome is binary for each participant: a participant either met the complete or partial response definition during the assessment period or did not. The group response percentage expresses the proportion meeting that definition. The registry reports 31.0% for gemcitabine, cisplatin and cetuximab and 20.0% for the same regimen plus cixutumumab. The corresponding group denominators are 29 and 25. These percentages should be read as estimates from the participants included in the reported efficacy groups, rather than as fixed underlying rates that would necessarily recur in another study.

General statistical explanation: a proportion is subject to sampling variability. If a different set of participants were studied, the observed response percentages could differ even if the underlying response probabilities were unchanged. Confidence intervals express uncertainty in the estimated quantity, conditional on the statistical method and its assumptions.

How should the risk difference be read?

The risk difference compares the two response proportions by subtraction, with the posted comparison defined as cixutumumab group minus comparator group. The registry reports an estimate of -0.110 and a 95% confidence interval from -0.340 to 0.120. A value of zero represents no difference in the two underlying proportions. The interval includes zero, so the data are compatible with no difference as well as with differences in either direction. The estimate itself is not proof of a treatment effect; it is the observed contrast under the stated comparison.

General statistical explanation: the risk difference is an absolute measure. It describes how far apart two probabilities are on the probability scale, whereas a relative measure expresses one group in relation to the other. Absolute measures can be directly useful for describing the size of a group contrast, but their uncertainty depends on the observed data and the method used to form the interval.

Why are risk ratios and odds ratios also reported?

The registry lists a risk ratio of 0.644 with a confidence interval from 0.248 to 1.672, and an odds ratio of 0.556 with a confidence interval from 0.158 to 1.952. For a ratio measure, a value of one represents no relative difference. Both reported intervals include one, indicating substantial uncertainty about the relative contrast. The risk ratio compares probabilities; the odds ratio compares odds, which are a transformation of probabilities. They answer related but not identical questions, and can differ in magnitude. Neither should be read in isolation from the underlying response percentages and the risk-difference estimate.

These three measures are different summaries of the same underlying two-group response data, not separate experiments. Their estimates are correlated. Looking across them can help clarify whether conclusions depend on the choice of scale, but it does not create additional independent evidence. In this comparison, each measure is imprecise, and the intervals include the value corresponding to no difference for that measure.

What does the p-value add?

The registry reports an unadjusted p-value of 0.356. General statistical explanation: a p-value describes how unusual data at least as incompatible with a specified null hypothesis would be under that hypothesis and the test assumptions. It does not give the probability that the null is true, the probability that the alternative is true, or the size of a treatment effect. A p-value also does not communicate the full range of plausible effect sizes; the confidence interval is more informative for that purpose.

The word “unadjusted” means the posted value is not identified as adjusted for multiple comparisons. The registry record does not report a multiplicity procedure for this endpoint, so the p-value should not be presented as a multiplicity-adjusted result. The registry record also does not provide enough information to reconstruct the exact test, its assumptions or any covariate adjustment. The estimate and p-value are reported as posted, rather than recalculated from the summary statistics.

What are the limits of the analysis information?

The registry record identifies a randomized, open-label, stratified phase 2 trial, but does not report the statistical analysis plan, the stratification factors, missing-data rules, handling of participants who were not evaluable for response, or the method used to calculate the intervals and p-value. It records no analysis entries in the analysis count. That does not by itself establish which analyses were performed; it means the record does not give those analysis details in the posted material.

General statistical explanation: missing outcome data can affect an estimated response percentage if the probability of being unobserved is related to response. Methods such as excluding unevaluable participants, classifying them as nonresponders or using an imputation approach can lead to different estimates. Since the registry record does not state the handling rule, no particular method should be assumed.

The record also describes an amended protocol and says that efficacy data for the original carboplatin-based groups were not summarized as they were not considered relevant to the amended study objectives. That limits the scope of the available efficacy comparison. The response results concern the cisplatin-based groups only and do not establish the response rates for the original groups.

10. Confidence Intervals and Precision

The 95% confidence interval for the response risk difference extends from -0.340 to 0.120, around the posted estimate of -0.110. Its span includes zero and permits differences in either direction. In practical terms, the data are not precise enough to establish the direction or size of a response difference between the amended groups. The interval should be considered alongside the group response percentages, 31.0% and 20.0%, rather than as a stand-alone verdict.

The individual response estimates also have broad 95% confidence intervals: 14.2% to 47.9% for gemcitabine, cisplatin and cetuximab, and 4.3% to 35.7% for the group with cixutumumab added. These ranges reflect uncertainty in each group’s percentage. They are not prediction intervals for the response of an individual participant, and they do not show the full range of outcomes that might occur in a future trial.

The relative measures are also imprecise. The risk-ratio interval is 0.248 to 1.672, and the odds-ratio interval is 0.158 to 1.952. Each includes one, the value corresponding to no relative difference. The range of values compatible with the data is therefore wide on both absolute and relative scales.

General statistical explanation: a confidence interval is a range produced by a method that, under repeated use and its assumptions, would cover the underlying parameter at the stated rate. It does not mean there is a 95% probability that this particular fixed parameter lies inside the calculated interval. Wide intervals commonly signal that the data do not determine the effect precisely. They do not, on their own, establish that the true effect is large, small or absent.

The registry record does not state whether the intervals account for stratification, missing data or other analysis features. Their interpretation should therefore follow the posted estimates without assuming an unreported adjustment. The uncertainty is an important part of the result: the point estimate alone gives a much narrower impression than the range of values compatible with the data.

11. 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 based on the observed response effect, not the trial’s original design calculations. The assumptions listed for these illustrations are a two-sided significance level of 0.05, equal allocation between the two arms, and a normal approximation. The effect to detect is set to the stated fraction of the observed effect. The registry record does not report the original sample-size justification or the trial’s own design assumptions.

For the binary response comparison, the planning values are participants per arm. The displayed scenarios are planning for 100% of the observed effect, planning for 75% of the observed effect, and planning for 50% of the observed effect. At each scenario, the 80% power column gives the modeled number of participants per arm for an 80% chance of rejecting the null hypothesis under the stated assumptions if that scenario’s effect were the true effect. The 90% power column gives the corresponding number per arm for a 90% chance under those same assumptions.

The planning figures increase as the assumed effect becomes smaller: detecting a smaller difference generally requires more participants, all else held constant. The reported values are 244 and 326 participants per arm when planning for 100% of the observed effect; 450 and 602 when planning for 75%; and 1,045 and 1,399 when planning for 50%, for the 80% and 90% power targets respectively.

These figures are not observed power. They are prospective planning illustrations generated from an effect estimated in the trial and depend on the listed assumptions. They should not be read as the number enrolled, as the trial’s actual planned sample size, or as evidence that the study was designed around these scenarios. For time-to-event outcomes, the stated planning convention uses total events, but this primary binary-response planning comparison is expressed as participants per arm.

12. 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 = 0.310; treatment proportion p₁ = 0.200; average p̄ = 0.255.
2. First term: z_1−α/2 × √[2p̄(1−p̄)] = 1.96 × 0.6165 = 1.2084.
3. Second term: z_1−β × √[p₀(1−p₀) + p₁(1−p₁)] = 0.842 × 0.6116 = 0.5147.
4. n = (1.2084 + 0.5147)² / (-0.1103)² = 243.8, rounded up to 244 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 <- 0.310344827586207                          # control proportion
p1 <- 0.2                          # 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(870870)
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 = 244 (80% power), 326 (90% power)
 75% of observed effect: n per arm = 450 (80% power), 602 (90% power)
 50% of observed effect: n per arm = 1,045 (80% power), 1,399 (90% power)
power.prop.test: 243.8 
Simulated power at n = 244 per arm: 0.803 (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.

13. Multiplicity, Missing Data and Analysis Populations

The registry lists multiple secondary outcomes, including overall survival, progression-free survival, time to progression, duration of response, adverse events or deaths, immunogenicity and cixutumumab concentration measures. The primary response endpoint is therefore part of a broader outcome set. Testing several outcomes can increase the chance of at least one apparently unusual result by chance if each is interpreted without accounting for the family of tests. General statistical explanation: multiplicity procedures can control that risk, but they can also affect the precision or threshold used for individual conclusions.

The primary comparison is reported with an unadjusted p-value of 0.356. The registry record does not report a multiplicity adjustment, a hierarchy of hypotheses or a family-wise analysis plan. Consequently, the posted result should not be described as adjusted for testing multiple outcomes. The record lists 14 secondary outcomes as posted but does not provide their numerical results in the registry record for this account; multiplicity across those results cannot be assessed from the response figures alone.

Missing-data handling is also not reported in the registry record. The primary endpoint definition uses participants treated as the denominator, and the posted groups have denominators of 29 and 25. The record does not state how participants with missing assessments, early withdrawal, or no evaluable scan were treated, nor does it describe imputation or sensitivity analyses. These omissions prevent a full assessment of whether missing response assessments could alter the estimates.

The primary population is described as all participants randomized to the amended gemcitabine, cisplatin and cetuximab groups, with or without cixutumumab, while the endpoint calculation description refers to participants treated. The registry record does not explain the operational relationship between those descriptions or identify a separate per-protocol or intention-to-treat analysis. It also does not report a detailed participant flow or analysis populations for the response outcome. These points matter because analysis population choices can affect the denominator and the interpretation of a randomized comparison.

The record gives no posted analysis entries. This absence does not establish that no analysis was conducted, but it means analysis specifications and results beyond the reported summaries are not available in the registry record. Conclusions should remain limited to the reported response estimates and their stated uncertainty.

14. Safety Results

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

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: thrombocytopenia (100.0%), disease progression (25.0%), dyspnoea (25.0%), pulmonary embolism (25.0%), stomatitis (16.7%).

The serious adverse event figures are reported separately for the original carboplatin-based groups and the amended cisplatin-based groups. In the gemcitabine, cisplatin and cetuximab group, 20 of 29 participants were recorded as having a serious adverse event; in the group with cixutumumab, 15 of 25 were recorded. The original gemcitabine, carboplatin and cetuximab group lists 4 of 4, and its cixutumumab group lists 5 of 6. These group counts should not be combined: they relate to different regimens and protocol periods.

The listed serious adverse event terms include thrombocytopenia at 100.0%, disease progression at 25.0%, dyspnoea at 25.0%, pulmonary embolism at 25.0%, stomatitis at 16.7% and infusion related reaction at 16.7%. The registry record does not clarify the denominator or calculation basis for these term percentages, so they should be read as the posted percentages rather than treated as participant-level risks across a specified treatment group.

Death counts are not reported in the registry record. These adverse event summaries are descriptive and do not establish a causal treatment comparison. The record does not provide the detail needed to compare event severity, timing, exposure or adjusted risks.

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

The posted primary result describes a lower observed response percentage in the cixutumumab group than in the comparator group: 20.0% versus 31.0%. The risk-difference estimate is -0.110, but its 95% confidence interval, -0.340 to 0.120, includes zero and extends in both directions. The result therefore leaves substantial uncertainty about the direction and size of any difference in objective response between these amended treatment groups.

That uncertainty is not evidence that the groups are equivalent. A finding of equivalence or noninferiority would require a defined margin and a design and analysis intended to evaluate that question. The registry record does not report such a margin or analysis. Nor does the result establish that cixutumumab has no effect. It indicates that the available response data, as reported, do not precisely determine the comparative response effect.

The endpoint measures complete or partial response under RECIST version 1.0 during the stated assessment period. It does not directly measure survival, time without progression, response duration, quality of life or the overall balance of benefits and harms. Although several of these outcomes are listed as secondary outcomes, their numerical results are not reported in the registry record used for these response figures. Safety information is also limited to the posted adverse-event counts and terms, with death counts not reported.

The efficacy findings apply to the amended gemcitabine, cisplatin and cetuximab groups, with and without cixutumumab. They do not provide efficacy estimates for the original carboplatin-based arms, whose response summaries were not included under the amended protocol. The open-label design and absent detail on response assessment, missing data and analysis procedures are additional constraints on interpretation.

Overall, the data describe a response comparison with broad uncertainty, not a definitive determination of clinical benefit or harm. They should not be translated into advice for an individual or a general claim about treatment effectiveness. A fuller judgment would require other trial outcomes, their analysis details, and clinical context that are not reported in the registry record.

16. Why This Trial Matters Statistically

This trial illustrates how a clinically interpretable endpoint can still yield an uncertain comparison. Objective response has a clear operational definition: complete disappearance of lesions with the stated marker normalization, or a partial reduction in target lesion measurements under RECIST version 1.0. That definition allows the response outcome to be expressed as a percentage, but the estimate remains subject to sampling variability and depends on the analysis population and assessment process.

The study also highlights the importance of protocol amendments when reading registry results. The official title refers to carboplatin, while the arm descriptions state that cisplatin replaced carboplatin. The efficacy results focus on the amended cisplatin-based groups, and the record says that efficacy summaries for the original carboplatin-based groups were not considered relevant to the amended objectives. Readers must therefore match each estimate to the regimen and population it actually describes rather than assume that all listed arms contribute to one comparison.

Statistically, the point estimate should not overshadow the confidence interval. The posted risk difference is negative, but the interval includes zero and allows effects in either direction. The relative measures are similarly imprecise. This is a useful example of why effect estimates, intervals and p-values answer different questions: the estimate gives a central contrast, the interval conveys uncertainty about its magnitude, and the p-value assesses compatibility with a specified null model under test assumptions.

The registry record also separates trial results from planning illustrations. Sample-size scenarios based on the observed effect can help describe the scale of a future planning exercise, but they are not the trial’s original design assumptions and are not observed power. Keeping those distinctions clear prevents retrospective calculations from being mistaken for evidence about how the trial was planned or what it could reliably detect.

Finally, the record illustrates how incomplete analysis reporting limits interpretation. Missing-data rules, multiplicity methods, stratification details and results for secondary outcomes are not reported in the registry record. A statistically careful reading identifies these gaps instead of filling them with assumptions.

17. 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.
• Participant counts were reconstructed from posted percentages and arm sizes, so small rounding differences are possible.

The efficacy comparison is restricted to the amended gemcitabine, cisplatin and cetuximab groups, with and without cixutumumab. The registry states that efficacy data were not summarized for the original gemcitabine, carboplatin and cetuximab groups because they were not considered relevant after the protocol amendment. The response findings therefore cannot be generalized to the original carboplatin-based comparison using these results.

The registry records enrollment of 64, while the response groups have denominators of 29 and 25. The record does not give a participant flow or reconcile these numbers, so the relationship between enrollment and the reported efficacy populations cannot be determined from the posted information. It also does not state how missing or unevaluable response assessments were handled, or whether the endpoint denominator was based on all randomized participants, treated participants or another analysis population in practice.

The trial was open label, and the registry record does not say whether response assessments were independently reviewed or blinded to treatment. The method of allocation, stratification factors, assessment schedule and statistical analysis plan are also not reported. Without those details, the impact of assessment procedures and analysis choices cannot be evaluated fully.

The reported intervals are broad, and the risk-difference interval includes zero. This limits precision about both the direction and magnitude of the response contrast. The registry record does not report a prespecified equivalence or noninferiority margin, so the result should not be treated as evidence of equivalence. The original sample-size assumptions and justification are not reported either.

Finally, the registry lists several secondary outcomes but does not provide their numerical results in this record. The serious adverse event data are descriptive, the basis for the listed event-term percentages is not stated, and death counts are not reported in the registry record. These omissions limit conclusions about survival, durability, safety comparisons and the broader balance of outcomes.

18. Related Tutorials

19. Related Statistical Calculators

20. Sources

• ClinicalTrials.gov: A Study of IMC-A12 (Cixutumumab) With and Without Other Standard Chemotherapies in Participants With Lung Cancer Who Have Not Received Chemotherapy Before — NCT00870870.
• Registry record last updated 2018-06-01; status last verified 2018-05.
• Results first posted 2018-06-01.
• 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.

21. Record Summary

NCT00870870 is a completed, randomized, open-label, parallel-group phase 2 trial sponsored by Eli Lilly and Company. It studied chemotherapy-naive participants with advanced or metastatic non-small cell lung cancer. The primary endpoint was objective response, defined as complete or partial response under RECIST version 1.0.

Primary efficacy results are reported for the amended gemcitabine, cisplatin and cetuximab groups, with or without cixutumumab. Response was 31.0% in the comparator group and 20.0% in the cixutumumab group. The risk difference was -0.110, with a 95% confidence interval from -0.340 to 0.120 and an unadjusted p-value of 0.356. The interval includes no difference and reflects substantial uncertainty.

The registry record does not report efficacy summaries for the original carboplatin-based groups, the trial’s original sample-size assumptions, detailed missing-data rules or numerical results for the listed secondary outcomes. The posted findings should be interpreted as a response comparison in the amended groups, not as a complete account of survival or safety outcomes.