This page provides an independent statistical analysis and educational interpretation of publicly reported results. ClinicalTrials.gov provides the official trial registry record. Numerical trial results on this page are restricted to the results posted in the ClinicalTrials.gov record; calculations added by Clinical Biostats are labelled as such.
1. Trial at a Glance
This page covers the registry results for TIGER-1: Safety and Efficacy Study of Rociletinib (CO-1686) or Erlotinib in Patients With EGFR-mutant/Metastatic NSCLC Who Have Not Had Any Previous EGFR Directed Therapy (NCT02186301), a randomized phase 2, phase 3 study. The primary outcome is Progression Free Survival (PFS) According to RECIST Version 1.1 as Determined by Investigator Review (invPFS).
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT02186301 |
| Phase | Phase 2, Phase 3 |
| Condition | Non-Small Cell Lung Cancer |
| Allocation | Randomized |
| Design model | Parallel |
| Masking | None (open label) |
| Enrollment | 100 |
| Arms in the primary outcome | 3 |
| Lead sponsor | Clovis Oncology, Inc. |
| Results posted | Yes |
2. Clinical Question
TIGER-1 asked whether first-line treatment with oral rociletinib or erlotinib differed in progression-free survival for patients with EGFR-mutant advanced or metastatic non-small cell lung cancer who had not previously received EGFR-directed therapy. The registry describes the study as randomized and open-label, with patients assigned to rociletinib or erlotinib. Rociletinib was studied at two tablet doses, so the posted results distinguish two rociletinib groups rather than presenting a single pooled rociletinib result.
Population
Patients with EGFR-mutant advanced or metastatic NSCLC who had not previously received EGFR-directed therapy. The primary endpoint population is described as all randomized patients, with one patient excluded from analysis after discontinuing shortly after randomization and before receiving study drug.
Intervention
Oral rociletinib, reported separately as 500mg tablets and 625mg tablets. The study summary describes rociletinib dosing as twice a day.
Comparator
Oral erlotinib, reported as 150mg tablets. The study summary describes erlotinib dosing as once a day.
Primary question
How did investigator-assessed progression-free survival, measured using RECIST version 1.1, compare across the rociletinib dose groups and erlotinib? The registry reports group-specific medians and confidence intervals, but a direct primary-endpoint comparison is not reported in the registry record.
The comparison is clinically framed as a first-line targeted-treatment question, but the posted primary results are descriptive group estimates rather than an inferential treatment contrast. The registry record does not report a hazard ratio or a primary-endpoint p-value. The secondary outcomes listed include confirmed response rate and duration of response; the available posted secondary results do not provide numerical duration-of-response results.
3. Trial Design
TIGER-1 (NCT02186301) is recorded as a randomized, parallel-group study with no masking. Its phase is listed as Phase 2 and Phase 3. The sponsor is Clovis Oncology, Inc. The registry lists enrollment as 100, the study start as 2014-11, primary completion as 2017-06-28, and status as terminated. The reason for termination is not reported in the registry record.
The study compared rociletinib monotherapy with erlotinib monotherapy. The posted primary endpoint results distinguish rociletinib 500mg tablets, rociletinib 625mg tablets, and erlotinib 150mg tablets. The summary describes patients as randomly assigned to rociletinib twice a day or erlotinib once a day, continuing treatment until it was no longer beneficial. The detailed protocol for assignment, treatment changes, and discontinuation is not reported in the registry record.
The primary outcome was progression-free survival measured in days from Cycle 1 Day 1 to the end of treatment, up to approximately 35 months. Progression was assessed by investigator review under RECIST version 1.1. The registry reports Kaplan-Meier median estimates by group. The analysis population is described as intent-to-treat, meaning all randomized patients, but the record also states that one patient was not included in the analysis because study discontinuation occurred shortly after randomization and before the first dose.
The record gives primary-endpoint group sizes of 18 for rociletinib 500mg, 30 for rociletinib 625mg, and 50 for erlotinib. The confirmed-response endpoint has its own group denominators, which are not identical for the rociletinib 500mg group. These endpoint-specific denominators should not be treated as interchangeable. Randomization details, allocation concealment, stratification factors, the sample-size justification, and any interim-analysis plan are not reported in the registry record.
4. Participant Flow and Accounting
The registry reports how participants moved through each stage of the study. All counts below are exactly as posted; missing counts are not inferred from other stages.
Overall Study
| Stage | Rociletinib 500mg Tablets | Rociletinib 625mg Tablets | Erlotinib 150mg Tablets |
|---|---|---|---|
| STARTED | 20 | 30 | 50 |
| COMPLETED | 0 | 0 | 0 |
| NOT COMPLETED | 20 | 30 | 50 |
Reasons for not completing this period:
| Reason | Rociletinib 500mg Tablets | Rociletinib 625mg Tablets | Erlotinib 150mg Tablets |
|---|---|---|---|
| Progressive Disease | 7 | 22 | 27 |
| Adverse Event | 5 | 5 | 5 |
| Death | 1 | 0 | 0 |
| Withdrawal by Subject | 5 | 1 | 3 |
| Physician Decision | 1 | 0 | 1 |
| Study Terminated by Sponsor | 1 | 0 | 11 |
| Protocol Deviation | 0 | 2 | 0 |
| Missing | 0 | 0 | 2 |
| Other | 0 | 0 | 1 |
Analysis population for the primary outcome, as defined in the registry: Intent-to-treat: All patients randomized. 1 patient was not included in analysis, due to discontinuation of study shortly after randomization and prior to first dose of study drug.
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.
| Characteristic | Unit | Rociletinib 500mg Tablets | Rociletinib 625mg Tablets | Erlotinib 150mg Tablets | Total |
|---|---|---|---|---|---|
| Participants analysed | 20 | 30 | 50 | 100 | |
| Age, Customized | years | 66.0 (44 to 86) | 67.0 (41 to 85) | 64 (39 to 88) | 65 (39 to 88) |
| Sex: Female, Male: Female | Participants | 17 | 18 | 32 | 67 |
| Sex: Female, Male: Male | Participants | 3 | 12 | 18 | 33 |
| Ethnicity (NIH/OMB): Hispanic or Latino | Participants | 0 | 3 | 6 | 9 |
| Ethnicity (NIH/OMB): Not Hispanic or Latino | Participants | 19 | 27 | 43 | 89 |
| Ethnicity (NIH/OMB): Unknown or Not Reported | Participants | 1 | 0 | 1 | 2 |
| Race/Ethnicity, Customized: American Indian or Alaska Native | Participants | 0 | 0 | 0 | 0 |
| Race/Ethnicity, Customized: Asian | Participants | 9 | 15 | 25 | 49 |
| Race/Ethnicity, Customized: Black or African American | Participants | 2 | 2 | 1 | 5 |
| Race/Ethnicity, Customized: Native Hawaiian or Other Pacific Islander | Participants | 0 | 0 | 0 | 0 |
| Race/Ethnicity, Customized: White | Participants | 9 | 12 | 21 | 42 |
| Race/Ethnicity, Customized: Other | Participants | 0 | 0 | 1 | 1 |
| Race/Ethnicity, Customized: Missing | Participants | 0 | 1 | 2 | 3 |
| Race/Ethnicity, Customized: White | Participants | 9 | 12 | 21 | 42 |
| Race/Ethnicity, Customized: Asian | Participants | 9 | 15 | 25 | 49 |
| Race/Ethnicity, Customized: Non-White, Non-Asian | Participants | 2 | 3 | 4 | 9 |
| Number of Previous Therapies | units on a scale | 0.0 (0.0 to 1.0) | 0.0 (0.0 to 2.0) | 0.0 (0.0 to 1.0) | 0.0 (0.0 to 2.0) |
| Time Since Diagnosis of NSCLC | months | 7.2 (SD 14.12) | 5.3 (SD 10.39) | 8.2 (SD 21.83) | 7.1 (SD 17.57) |
| History of CNS Metastases | Participants | 1 | 1 | 2 | 4 |
6. Primary Endpoint
The registry lists the primary outcome as Progression Free Survival (PFS) According to RECIST Version 1.1 as Determined by Investigator Review (invPFS), measured over Cycle 1 Day 1 to End of Treatment, up to approximately 35 months.
| Element | Registry entry |
|---|---|
| Result type | Median |
| Measure of spread | 95% Confidence Interval |
| Unit | Days |
| Endpoint classification | Time-to-Event Analysis |
Progression-free survival (PFS) measures the time from the start of treatment until disease progression or death, according to the endpoint definition used by a trial. TIGER-1 defined progression using RECIST version 1.1 and investigator review. Progression included a specified increase in the sum of target-lesion diameters relative to the smallest sum on study, with an absolute increase requirement, or the appearance of one or more new lesions. This endpoint is used in cancer trials because it captures the time until a clinically defined worsening event or death, rather than relying only on whether a participant’s disease shrinks at a particular assessment.
The registry reports median PFS in days, estimated using Kaplan-Meier methods, with 95% confidence intervals. A median is the time by which an estimated half of the group has experienced the event; it is not an average duration for every participant. A confidence interval conveys uncertainty around the estimate. The registry reports 274.0 days for rociletinib 500mg tablets, with a 95% confidence interval lower bound of 109 and an upper bound not reported in the registry record. For rociletinib 625mg tablets, the median is 207.0 days (95% CI 112.0 to 260.0); for erlotinib 150mg tablets, it is 390 days (95% CI 282.0 to 499.0).
These are group-specific estimates. Without a reported hazard ratio or other direct comparison, they do not by themselves quantify the relative treatment effect or establish the precision of a between-group contrast.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The primary results are Kaplan-Meier median PFS estimates for three treatment groups. The registry reports 274.0 days for rociletinib 500mg tablets, 207.0 days for rociletinib 625mg tablets, and 390 days for erlotinib 150mg tablets. The confidence intervals are also reported by group, although the upper bound for the 500mg rociletinib estimate is not reported in the registry record. These estimates describe the observed time-to-event distributions in the analyzed groups; they are not, on their own, a formal test of whether one treatment differs from another.
The registry record does not report a hazard ratio, a p-value, or a direct inferential comparison for the primary endpoint. A difference between medians is not a substitute for a treatment-effect estimate based on the full time-to-event data. The median focuses on one point of the survival curve, while a hazard ratio would summarize the relative event rate over follow-up under its modeling assumptions. Neither a hazard ratio nor a comparison confidence interval should be inferred from the group medians.
Precision is an important part of interpretation. Confidence intervals describe uncertainty in the estimated group medians, and the reported intervals are not equally complete: the upper confidence bound for rociletinib 500mg is missing from the registry record. The analysis group sizes are 18, 30, and 50, respectively. Smaller groups generally yield less precise estimates as a general statistical principle, but no new interval or between-group precision estimate can be recovered from these medians alone.
The registry describes the primary population as all randomized patients, while also noting that one patient was excluded after discontinuing shortly after randomization and before receiving study drug. That qualification matters when interpreting the phrase intent-to-treat: the stated analysis population and the stated exclusion do not fully align with a strict all-randomized analysis. The record does not explain any further handling of missing follow-up or censoring.
Overall, the posted primary data establish the reported group-specific median estimates, not a definitive comparative conclusion. The study was open-label, and the primary endpoint was assessed by investigators. The record does not report the procedures used to reduce potential assessment bias, the planned primary contrast, or a statistical testing strategy. The status is terminated, but the reason and its implications for the final analyses are not reported in the registry record. Interpretation should therefore remain tied to the posted estimates and their documented limitations.
9. Statistical Methods Explained
The primary endpoint is a time-to-event outcome. For this kind of endpoint, some participants may not experience progression or death during their observed follow-up. Kaplan-Meier estimation is a general method for describing the probability of remaining event-free over time while accounting for incomplete follow-up through censoring. Censoring means that the event time is not observed for a participant during the available observation period; it does not mean that the participant experienced the event at the last observed time. The registry reports Kaplan-Meier medians, but the detailed censoring rules and follow-up procedures are not reported in the registry record.
A median time-to-event estimate identifies the point at which the estimated event-free proportion reaches one half. It is a summary of the estimated curve, not a statement that every participant had an event at that time. In TIGER-1, the registry reports medians in days and 95% confidence intervals for the three groups. Confidence intervals express uncertainty in an estimate under the analysis method. They do not indicate the range of individual participants’ PFS times, and a confidence interval for a group median is not itself a confidence interval for the difference between two medians.
The primary endpoint is defined by a specific progression rule. Under the registry description of RECIST version 1.1, progression includes at least a 20% increase in the sum of the longest diameters of target lesions from the smallest sum on study, together with an absolute increase of at least 5 mm. Appearance of one or more new lesions also counts as progression. The endpoint was determined by investigator review. Because the study was open-label, investigators and participants were not masked to treatment assignment according to the registry. General statistical practice recognizes that knowledge of assignment can be relevant to outcome assessment, but the record does not describe additional review safeguards or independent confirmation for this primary endpoint.
The record presents separate estimates for rociletinib 500mg tablets, rociletinib 625mg tablets, and erlotinib 150mg tablets. These are three group-level summaries, not a single pooled rociletinib estimate. A two-arm comparison would require a stated contrast and an appropriate estimate of its uncertainty. The registry record does not report a primary-endpoint hazard ratio, p-value, or direct comparison. The analysis listing also indicates that a two-arm comparison is unavailable for this median-time endpoint. It would not be appropriate to create a treatment comparison by subtracting the posted medians or by deriving a hazard ratio from those medians.
The registry identifies the primary population as intent-to-treat, described as all patients randomized, but notes that one participant was not included because study discontinuation occurred shortly after randomization and before the first dose. An intent-to-treat analysis generally aims to analyze participants in their randomized groups, regardless of whether they fully follow assigned treatment. The exclusion described in this record is therefore important context. The record does not explain whether the participant had outcome follow-up, what censoring was applied, or whether any sensitivity analysis addressed the exclusion.
Confirmed response rate is a binary endpoint: each participant is classified according to whether a confirmed response occurred. A risk difference expresses the difference in response proportions between two groups. The posted recalculations for this endpoint are explicitly unadjusted comparisons based on summary statistics. Their p-values are unadjusted and should not be read as results from an adjusted or prespecified model. The registry's own reported response analyses are group-specific percentages for rociletinib 500mg and 625mg; a corresponding sponsor-reported percentage for erlotinib is not listed among those reported analyses. The study's formal analysis plan, including any adjustment variables or testing hierarchy, is not reported in the registry record.
Planning illustrations based on an observed effect answer a different question from trial results. They describe hypothetical participants per arm under stated assumptions, including two-sided significance level 0.05, equal allocation, and a normal approximation. Rows that plan for a fraction of the observed effect explore how sample-size requirements change if a future study targets a smaller effect. These illustrations are not the trial's original sample-size justification and are not observed power. The trial's own sample-size rationale is not reported in the registry record.
Multiplicity arises when several outcomes, treatment contrasts, doses, or analyses are examined. Repeated testing can increase the chance of a nominally small p-value occurring by chance. A prespecified hierarchy or other multiplicity procedure can address this issue, but the registry record does not report one. Any unadjusted secondary comparison therefore has a more limited role than a result interpreted under a documented confirmatory testing plan. General statistical interpretation also distinguishes statistical uncertainty from clinical importance; a p-value alone does not measure the size or relevance of an effect.
10. Analyses Reported by the Sponsor
| Method | Estimate | 95% CI | P-value |
|---|---|---|---|
| not stated | Kaplan-Meier Median 274.0 | 109 to None | not reported |
| not stated | Kaplan-Meier Median 207.0 | 112.0 to 260.0 | not reported |
| not stated | Kaplan Meier Median 390 | 282.0 to 499.0 | not reported |
The sponsor-reported primary analyses give Kaplan-Meier median PFS estimates for each group: 274.0 days for rociletinib 500mg tablets, 207.0 days for rociletinib 625mg tablets, and 390 days for erlotinib 150mg tablets. The reported confidence intervals are 109 to an upper bound not reported in the registry record for rociletinib 500mg, 112.0 to 260.0 for rociletinib 625mg, and 282.0 to 499.0 for erlotinib. The registry does not list a sponsor-reported hazard ratio or direct primary-endpoint comparison.
For confirmed response, the registry lists sponsor-reported percentages and 95% confidence intervals for the rociletinib groups. It does not list a sponsor-reported result for erlotinib among those reported analyses. The recalculated comparisons elsewhere are unadjusted contrasts derived from posted summary statistics, rather than the sponsor's own comparative analysis. They do not replace a prespecified trial analysis. The record indicates no discrepancy between its reported results and the recalculated values, but that does not supply missing primary-endpoint comparisons or an unreported statistical plan.
When sponsor analyses and simple recalculations differ, the sponsor's own analysis takes precedence. In this record, the key limitation is not a documented disagreement: it is the absence of a direct sponsor-reported primary comparison and of a reported erlotinib response analysis in the listed sponsor analyses. No additional model, adjustment, or interpretation should be attributed to the sponsor beyond what the registry record states.
11. Multiplicity, Missing Data and Analysis Populations
The registry record lists a primary endpoint and secondary outcomes, but it does not report a statistical analysis plan describing how the several endpoints, dose groups, or possible treatment contrasts were handled together. It also does not report a multiplicity adjustment, a testing hierarchy, or a distinction between confirmatory and exploratory analyses. This absence limits interpretation of the unadjusted secondary comparisons: without knowing which contrasts were prespecified and how repeated testing was addressed, an unadjusted p-value should not be treated as if it came from a controlled confirmatory procedure.
The record states that the primary analysis population was intent-to-treat, meaning all randomized patients, and then specifies that one participant was excluded after discontinuing shortly after randomization and before the first dose. It does not report the reason for that discontinuation, whether outcome information was available, or how missing data were handled. Nor does it describe the censoring rules used for PFS, the amount of incomplete follow-up, or sensitivity analyses for missing or censored observations. These omissions matter because time-to-event estimates depend on the follow-up and censoring information available for participants.
The registry record does not report the trial's sample-size justification, assumptions for a planned treatment effect, or a planned power calculation. The sample-size illustrations associated with observed secondary effects are hypothetical planning exercises, not evidence about the design that was used and not observed power. The record also does not report whether interim analyses occurred or whether any formal stopping rule was applied. The terminated status alone does not establish why the study ended or whether termination affected the planned analyses.
These are reporting gaps, not evidence that a particular method was or was not used. They mean that readers cannot verify from the registry record whether missing-data, multiplicity, and interim-analysis decisions followed a prespecified plan.
12. Safety Results
The registry reports serious adverse events as affected participants divided by participants at risk.
| Arm | Participants with serious adverse events | Participants at risk | Percentage |
|---|---|---|---|
| Rociletinib 500mg Tablets | 10 | 19 | 52.6% |
| Rociletinib 625mg Tablets | 15 | 30 | 50.0% |
| Erlotinib 150mg Tablets | 7 | 50 | 14.0% |
| Crossover From Erlotinib 150mg to Rociletinib 500mg | 0 | 1 | 0.0% |
| Crossover From Erlotinib 150mg to Rociletinib 625mg | 1 | 1 | 100.0% |
Deaths
| Arm | Deaths (participants affected of at risk) |
|---|---|
| Rociletinib 500mg Tablets | 3 of 19 |
| Rociletinib 625mg Tablets | 1 of 30 |
| Erlotinib 150mg Tablets | 2 of 50 |
| Crossover From Erlotinib 150mg to Rociletinib 500mg | 0 of 1 |
| Crossover From Erlotinib 150mg to Rociletinib 625mg | 0 of 1 |
Other (non-serious) adverse events
Participants with at least one non-serious event at or above the registry's 5% reporting threshold.
| Arm | Participants affected of at risk |
|---|---|
| Rociletinib 500mg Tablets | 19 of 19 |
| Rociletinib 625mg Tablets | 30 of 30 |
| Erlotinib 150mg Tablets | 50 of 50 |
| Crossover From Erlotinib 150mg to Rociletinib 500mg | 0 of 1 |
| Crossover From Erlotinib 150mg to Rociletinib 625mg | 1 of 1 |
Most frequent serious adverse event terms
| Event term | Organ system | Rociletinib 500mg Tablets | Rociletinib 625mg Tablets | Erlotinib 150mg Tablets | Crossover From Erlotinib 150mg to Rociletinib 500mg | Crossover From Erlotinib 150mg to Rociletinib 625mg |
|---|---|---|---|---|---|---|
| Pneumonia | Infections and infestations | 2 of 19 | 2 of 30 | 2 of 50 | 0 of 1 | 0 of 1 |
| Vomiting | Gastrointestinal disorders | 2 of 19 | 1 of 30 | 0 of 50 | 0 of 1 | 0 of 1 |
| Malignant neoplasm progression | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | 1 of 19 | 0 of 30 | 1 of 50 | 0 of 1 | 1 of 1 |
| Hyperglycaemia | Endocrine disorders | 1 of 19 | 1 of 30 | 0 of 50 | 0 of 1 | 0 of 1 |
| Nausea | Gastrointestinal disorders | 2 of 19 | 0 of 30 | 0 of 50 | 0 of 1 | 0 of 1 |
| Dehydration | Metabolism and nutrition disorders | 0 of 19 | 1 of 30 | 1 of 50 | 0 of 1 | 0 of 1 |
| Hyperglycaemia | Metabolism and nutrition disorders | 1 of 19 | 1 of 30 | 0 of 50 | 0 of 1 | 0 of 1 |
| Acute respiratory failure | Respiratory, thoracic and mediastinal disorders | 1 of 19 | 1 of 30 | 0 of 50 | 0 of 1 | 0 of 1 |
| Pleural effusion | Respiratory, thoracic and mediastinal disorders | 1 of 19 | 1 of 30 | 0 of 50 | 0 of 1 | 0 of 1 |
| Diabetic ketoacidosis | Endocrine disorders | 1 of 19 | 0 of 30 | 0 of 50 | 0 of 1 | 0 of 1 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Rociletinib 500mg Tablets | Rociletinib 625mg Tablets | Erlotinib 150mg Tablets | Crossover From Erlotinib 150mg to Rociletinib 500mg | Crossover From Erlotinib 150mg to Rociletinib 625mg |
|---|---|---|---|---|---|---|
| Diarrhoea | Gastrointestinal disorders | 7 of 19 | 15 of 30 | 33 of 50 | 0 of 1 | 0 of 1 |
| Combined Terms of Rash | Skin and subcutaneous tissue disorders | 5 of 19 | 4 of 30 | 43 of 50 | 0 of 1 | 0 of 1 |
| Rash | Skin and subcutaneous tissue disorders | 4 of 19 | 3 of 30 | 26 of 50 | 0 of 1 | 0 of 1 |
| Combined Terms of Hyperglycemia | Endocrine disorders | 10 of 19 | 16 of 30 | 3 of 50 | 0 of 1 | 0 of 1 |
| Fatigue | General disorders | 6 of 19 | 9 of 30 | 12 of 50 | 0 of 1 | 1 of 1 |
| Hyperglycaemia | Metabolism and nutrition disorders | 10 of 19 | 15 of 30 | 2 of 50 | 0 of 1 | 0 of 1 |
| Nausea | Gastrointestinal disorders | 10 of 19 | 8 of 30 | 7 of 50 | 0 of 1 | 1 of 1 |
| Cough | Respiratory, thoracic and mediastinal disorders | 5 of 19 | 6 of 30 | 13 of 50 | 0 of 1 | 1 of 1 |
| Decreased appetite | Metabolism and nutrition disorders | 5 of 19 | 5 of 30 | 9 of 50 | 0 of 1 | 1 of 1 |
| Dyspnoea | Respiratory, thoracic and mediastinal disorders | 4 of 19 | 7 of 30 | 7 of 50 | 0 of 1 | 1 of 1 |
Serious events with the highest arm-level rate: malignant neoplasm progression (100.0%), ejection fraction decreased (100.0%), nausea (10.5%), vomiting (10.5%), pneumonia (10.5%).
The registry reports serious adverse event counts by treatment group, along with the number at risk for the listed safety summaries. For the original treatment groups, serious adverse events were reported for 10 of 19 participants in rociletinib 500mg, 15 of 30 in rociletinib 625mg, and 7 of 50 in erlotinib 150mg. The record also lists crossover groups, each with one participant at risk; one crossover participant to rociletinib 625mg had a serious adverse event, while none was listed for the crossover to rociletinib 500mg. These safety denominators should be kept distinct from the primary-endpoint analysis group sizes.
The record lists serious adverse event terms and percentages, including malignant neoplasm progression and decreased ejection fraction at 100.0%, as well as nausea, vomiting, pneumonia, and diabetic ketoacidosis at lower listed percentages. The registry excerpt does not give the event counts or the term-specific denominators alongside those percentages, so those percentages should not be interpreted as the proportion of all randomized participants without further detail.
These figures are descriptive safety reports, not a randomized comparative safety analysis. Differences in counts may reflect group size and exposure as well as event occurrence; treatment exposure durations and detailed event attribution are not reported in the registry record. The counts alone do not establish causation or quantify comparative risk.
13. What the Result Does, and Does Not, Mean
The posted results mean that the registry contains group-specific Kaplan-Meier median PFS estimates for rociletinib 500mg, rociletinib 625mg, and erlotinib 150mg. Those medians and their reported confidence intervals describe the estimated time-to-event experience in the analyzed groups. The confirmed-response results likewise describe group-level response proportions, and the registry includes serious adverse event summaries for the treatment and crossover groups.
They do not, by themselves, establish a comparative primary treatment effect. No sponsor-reported hazard ratio, direct PFS comparison, or primary-endpoint p-value is reported in the registry record. A ranking of medians is not equivalent to a formal comparison based on the full time-to-event data. Likewise, the unadjusted secondary response comparisons are not equivalent to a prespecified, multiplicity-controlled confirmatory test.
The results also do not establish why the study was terminated, whether termination changed the planned analyses, or how missing outcome data were handled. The registry's statement that the primary population was all randomized patients is qualified by the exclusion of one patient before the first dose. The sample-size illustrations based on observed effects do not describe the trial's original design or demonstrate its power.
As a general statistical principle, uncertainty around an estimate matters alongside its point value, and conclusions should reflect both the analysis design and the completeness of the reporting. For TIGER-1, the group estimates and safety summaries can be described, but the registry record does not contain enough information to make a definitive comparative claim from the primary endpoint. These registry results should not be recast as treatment advice or as a complete account of the trial's statistical analysis.
14. Why This Trial Matters Statistically
TIGER-1 illustrates why a randomized design does not, by itself, make every posted result a direct treatment comparison. The registry records random assignment, but the available primary endpoint results are medians for separate treatment groups. A comparative claim ordinarily depends on an explicitly reported contrast and its uncertainty, and that primary comparison is not reported in the registry record. Group summaries can be informative while still leaving the central comparative question unresolved.
The study also reports two rociletinib dose groups. Keeping those groups distinct is important: a single pooled rociletinib estimate is not reported, and the separate medians should not be combined without a prespecified reason and an appropriate analysis. The endpoint-specific denominators also differ for the 500mg group between the primary and confirmed-response results, which reinforces the need to read each outcome with its own analysis population.
The registry lists the study as terminated and reports open-label investigator assessment of PFS. Neither fact explains the other: the reason for termination is not reported, and the record does not describe any assessment safeguards or changes to analysis plans. These features make transparent reporting of the endpoint definition, analysis population, missing-data approach, and planned comparisons especially important.
Finally, the secondary response estimates show why outcome hierarchy and multiplicity matter. A descriptive secondary pattern can add context, but without a reported testing plan it should not be used to fill the gap left by an unreported primary comparison. TIGER-1 is therefore a useful example of separating posted estimates, recalculated contrasts, and conclusions that require a documented inferential analysis.
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.
Several limitations specific to the registry record constrain interpretation. First, the status is terminated, but the reason for termination and its effect on enrollment, follow-up, or analysis are not reported. The record lists enrollment as 100, but the primary-endpoint analysis groups contain 18, 30, and 50 participants. The record does not explain this relationship beyond noting that one randomized participant was excluded from the primary analysis before receiving study drug. The confirmed-response denominators differ for rociletinib 500mg, and the reason for that difference is not reported.
Second, the primary endpoint is investigator-assessed in an open-label study. The registry does not report independent central review, masking of outcome assessors, or other procedures intended to address possible assessment bias. It also does not report the primary comparative estimate, such as a hazard ratio, or a direct comparison confidence interval. The upper confidence bound for the rociletinib 500mg median is not reported.
Third, details needed to evaluate the time-to-event analysis are absent: the registry does not report censoring rules, completeness of follow-up, missing-data handling, or sensitivity analyses. The reason for the exclusion from the stated intent-to-treat population is described only in relation to timing of discontinuation and first dose. The record also does not report a statistical analysis plan, multiplicity procedure, interim-analysis plan, or original sample-size justification.
Finally, duration of response is listed as a secondary outcome, but numerical results are not reported in the available record. Safety summaries include serious adverse events and selected terms, but detailed term-specific counts and denominators are not included alongside every listed percentage. These limitations concern the information available in the registry record and should not be interpreted as evidence about analyses that may or may not have been conducted elsewhere.
16. Related Tutorials
17. Related Statistical Calculators
18. Sources
- ClinicalTrials.gov: TIGER-1: Safety and Efficacy Study of Rociletinib (CO-1686) or Erlotinib in Patients With EGFR-mutant/Metastatic NSCLC Who Have Not Had Any Previous EGFR Directed Therapy — NCT02186301.
- Registry record last updated 2019-05-07; status last verified 2019-04.
- Results first posted 2019-04-30.
- 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.
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19. Record Summary
TIGER-1 (NCT02186301) was a randomized, open-label, parallel Phase 2/3 study of first-line rociletinib or erlotinib for EGFR-mutant advanced or metastatic NSCLC. The registry lists enrollment of 100, a study start of 2014-11, primary completion on 2017-06-28, and terminated status. The primary endpoint was investigator-assessed PFS under RECIST version 1.1, reported as Kaplan-Meier median days by treatment group.
The registry reports medians for rociletinib 500mg, rociletinib 625mg, and erlotinib 150mg, but no direct primary-endpoint comparison or hazard ratio. Confirmed response is also reported; numerical duration-of-response results are not reported in the registry record. Interpretation is limited by the open-label design, an exclusion from the stated all-randomized analysis population, and missing details about the statistical plan, multiplicity, missing data, and reason for termination.