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 A Study of Tarceva (Erlotinib) Monotherapy in Patients With Advanced Non-Small Cell Lung Cancer (NSCLC) (NCT01996332), a non-randomized phase 2 study. The primary outcome is Time to Disease Progression or Death by Line of Treatment.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT01996332 |
| Phase | Phase 2 |
| Condition | Non-Small Cell Lung Cancer |
| Allocation | Non-Randomized |
| Design model | Single Group |
| Masking | None (open label) |
| Enrollment | 1805 |
| Arms in the primary outcome | n/a |
| Lead sponsor | Hoffmann-La Roche |
| Results posted | Yes |
2. Clinical Question
Population
The study concerned patients with advanced non-small cell lung cancer for whom Tarceva monotherapy was considered the best option. The primary outcome description identifies the analysis population as the ITT population and says results were analyzed across six treatment-line cohorts.
Intervention
Participants received erlotinib, marketed as Tarceva, as monotherapy. The adverse-event record names the regimen as erlotinib 150 mg/day. The study summary describes oral treatment and anticipates treatment on study for 3-12 months; that anticipated duration is not an observed treatment duration.
Comparator
The design is recorded as single-group and non-randomized, with no masking. There is no randomized control group described. Treatment-line cohorts are categories within the study population, not established like-for-like treatment arms.
Primary question
The primary outcome asks how long it took from inclusion until disease progression or death, whichever occurred first, among patients receiving erlotinib. The outcome was to be summarized by treatment line. The registry record does not report the cohort-specific median estimates or their confidence intervals, so it does not provide the numerical answer to that question.
3. Trial Design
This completed phase 2 study evaluated erlotinib monotherapy in patients with advanced non-small cell lung cancer. The named sponsor was Hoffmann-La Roche. The registry records enrollment of 1805, a start date of 2004-04, and primary completion in 2012-10. The study was open-label, non-randomized, and single-group; masking was recorded as none.
The intervention was oral Tarceva, also called erlotinib. The brief study summary says anticipated time on study treatment was 3-12 months. This is a planned expectation in the summary, not a reported distribution of actual treatment duration. The adverse-event group is labeled erlotinib 150 mg/day.
The primary outcome was time to disease progression or death, with the time interval beginning at inclusion. The registry describes assessment at baseline and every 6-8 weeks up to 3 years until progression or death. Results were to be considered in the ITT population and analyzed in six cohorts defined by line of treatment: first line; maintenance after first line; second line; maintenance after second line; third or subsequent line; and maintenance after third line.
The registry also lists clinical benefit and overall survival by line of treatment as secondary outcomes. It does not report numerical results for these outcomes in the record described. Because the study has no randomized comparator, comparisons among treatment-line cohorts cannot by themselves isolate the effect of erlotinib from differences in patient characteristics, disease course, or prior treatment. The record does not report a protocol-based sample-size justification or further details about how cohort membership was assigned.
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: Three cohorts were established in participants with advanced non-small cell lung cancer (NSCLC) based on previous chemotherapy treatment received: first line of treatment (where conventional chemotherapy is not indicated), second line of treatment, and third and subsequent lines of treatment. Inclusion was competitive.
Overall Study
| Stage | Erlotinib 150 Milligrams Per Day (mg/Day) |
|---|---|
| STARTED | 1805 |
| COMPLETED | 0 |
| NOT COMPLETED | 1805 |
Reasons for not completing this period:
| Reason | Erlotinib 150 Milligrams Per Day (mg/Day) |
|---|---|
| Adverse Event | 117 |
| Lack of Efficacy | 1245 |
| Death | 264 |
| Protocol Violation | 9 |
| Withdrawal by Subject | 71 |
| Other | 20 |
| Clinical Deterioration | 28 |
| Physician Decision | 17 |
| Lost to Follow-up | 34 |
Analysis population for the primary outcome, as defined in the registry: ITT Population; data were analyzed in 6 cohorts, with erlotinib treatment as: 1) first line; 2) maintenance after first line; 3) second line; 4) maintenance after second line; 5) third or subsequent line; or 6) maintenance after third line
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: Intent-to-treat (ITT) population defined as all participants included to each of three cohorts based on prior chemotherapy treatment received: first-line monotherapy (for whom conventional chemotherapy was not indicated), second-line monotherapy, and third or subsequent lines of treatment.
| Characteristic | Unit | Erlotinib 150 mg/Day |
|---|---|---|
| Participants analysed | 1805 | |
| Age, Continuous | years | 63.55 (SD 11.75) |
| Sex: Female, Male: Female | Participants | 520 |
| Sex: Female, Male: Male | Participants | 1285 |
6. Primary Endpoint
The registry lists the primary outcome as Time to Disease Progression or Death by Line of Treatment, measured over Baseline, every 6-8 weeks up to 3 years until disease progression or death.
| Element | Registry entry |
|---|---|
| Result type | Median |
| Measure of spread | 95% Confidence Interval |
| Unit | months |
| Endpoint classification | Time-to-Event Analysis |
The primary endpoint is time from inclusion to disease progression or death, whichever occurred first. It is a time-to-event measure: rather than recording only whether an event occurred, it incorporates when the first qualifying event was recorded. Patients who experience either progression or death have an event under this definition.
The registry specifies that the endpoint was assessed from baseline, with assessments every 6-8 weeks up to 3 years until progression or death. It names the median and a 95% confidence interval as the summary measures and says the outcome was analyzed by treatment line in the ITT population. The record does not report the actual median values or confidence intervals for the cohorts.
In general, a median time-to-event estimate describes the point by which half of the analyzed population has experienced the event, subject to the analysis method and available follow-up. A confidence interval conveys uncertainty around an estimate; it is not a range containing most individual event times. Combining progression and death into one endpoint captures either event as the first event of interest, but does not show which component accounts for the result. The registry record does not report separate component estimates.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The registry identifies a clinically interpretable primary outcome: time from inclusion to the first of disease progression or death. It also specifies a median with a 95% confidence interval and analysis by treatment line. However, the outcome description is not accompanied by cohort-specific estimates in the record. The median values and confidence intervals are therefore not reported in the registry record, and the primary outcome cannot be quantitatively characterized from the information available.
This distinction matters. A stated endpoint definition tells readers what was intended to be measured; it does not establish the observed duration or the precision of an estimate. Without the medians and confidence intervals, it is not possible to describe the size or uncertainty of the observed time-to-event results. The record also does not report a hazard-ratio estimate for the primary outcome. No numerical efficacy conclusion should be inferred from the study title, summary, or endpoint name.
The six treatment-line cohorts offer a way to organize results according to treatment context. They do not create a randomized comparison. Patients in different lines or maintenance settings may differ in prior treatment and clinical course, among other factors. A difference between cohort summaries, if reported, would therefore be descriptive and could not be attributed to treatment-line placement alone on the basis of this design.
The study is recorded as single-group and non-randomized. There is no concurrent randomized control group described against which to distinguish outcomes under erlotinib from outcomes that might have occurred under another treatment or without the study intervention. The registry record consequently supports a description of the study question and recorded safety information, but not a controlled estimate of comparative treatment effect.
The listed secondary outcomes are clinical benefit and overall survival, both by line of treatment. Their numerical results are not reported in the registry record. Nor does the record state the specific operational definition of clinical benefit, the analysis details for overall survival, or the results for separate progression and death components. These omissions limit interpretation beyond the endpoint definition itself.
Safety entries include counts of participants with serious and other adverse events and percentages for selected serious-event terms. These figures describe events recorded in the study; without a comparison group and fuller details about ascertainment, follow-up, and attribution, they do not establish that the intervention caused an event or permit direct comparative safety conclusions.
9. Statistical Methods Explained
The primary outcome is a time-to-event endpoint. In general, such methods are used when the timing of an event matters and some participants may not have an event recorded during their observed follow-up. The event in this study is the first occurrence of disease progression or death. The registry defines the clock as starting at inclusion and reports planned assessments at baseline and every 6-8 weeks up to 3 years, until progression or death.
What does the median represent?
The registry names the median as the primary summary. In general, the median time-to-event estimate marks the time by which half of the analyzed population is estimated to have experienced the event. It is not an average and does not describe the range of individual experiences. Time-to-event analyses can use information from participants who have not yet experienced the event by the end of their observation, provided their follow-up and event status are appropriately handled. The specific method used to estimate the medians is not reported in the registry record.
How should a confidence interval be read?
The primary outcome is specified with a 95% confidence interval. In general, a confidence interval communicates the statistical uncertainty around an estimate under the assumptions of the analysis. A narrower interval indicates greater precision than a wider interval, while neither interval width nor the estimate alone establishes whether an observed result is clinically important. The cohort-specific estimates and intervals are not reported in the registry record, so their precision cannot be assessed.
What does the endpoint combine?
Progression or death is a composite event definition: either component qualifies as an event, and the first one recorded determines the endpoint time. This can provide a single summary of time until worsening disease or death, but it does not show whether a result is driven mostly by progression, death, or both. Separate component estimates are not reported in the registry record. The timing and frequency of scheduled assessments can also affect when progression is documented; the record gives the assessment schedule but does not describe the progression criteria or adjudication procedures.
What do the treatment-line cohorts add?
The ITT population was analyzed in six cohorts based on treatment line or maintenance after a treatment line. In general, grouping results this way can describe outcomes in distinct treatment contexts. It does not make those groups randomized or comparable. Differences in their outcome summaries could reflect differences in patient characteristics, prior treatment, or clinical course as well as other factors. The registry does not report cohort-specific estimates in the information available, nor does it give details of cohort assignment beyond the listed categories.
Why is a hazard ratio different?
In general, a hazard ratio compares event rates over follow-up between groups under a model, whereas a median describes a time point in an event-time distribution. A hazard ratio needs a comparator group and relies on modeling assumptions, including assumptions about how the relative event rate behaves over time. This study is recorded as single-group, so a treatment-versus-control hazard ratio is not established by its design. The registry record does not report a primary-outcome hazard-ratio estimate. The posted outcome specification instead names medians and confidence intervals.
What can planning calculations say?
In general, sample-size calculations are planning illustrations tied to assumptions about the effect to detect, significance level, allocation, and analysis method. They are not evidence that a study had a particular probability of detecting its observed result. The planning illustration associated with this record uses a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation; for time-to-event outcomes it describes total events. Those are illustration assumptions, not the recorded design of this single-group study. Any such illustration is not observed power, and it does not replace a trial-specific design justification, which is not reported in the registry record.
Interpretation also depends on how follow-up, censoring, missing assessments, and event dates were handled. These are important general features of time-to-event analysis because an incomplete record of follow-up can affect estimated event times and uncertainty. The registry record does not report the specific censoring rules, missing-data procedures, statistical model, or software used for the primary analysis.
10. Multiplicity, Missing Data and Analysis Populations
The primary outcome was analyzed across six treatment-line cohorts, and the registry lists two secondary outcomes: clinical benefit and overall survival by line of treatment. Looking at several outcomes or subgroups can raise the general statistical issue of multiplicity: with more opportunities to assess results, the chance of at least one apparently notable finding can increase. The registry record does not report a multiplicity adjustment, a hierarchy for testing outcomes, or a prespecified strategy for interpreting cohort-specific comparisons.
The record lists no analysis entries. It also does not report numerical results for the primary or secondary outcomes in the information available. A lack of reported analysis details does not establish that no analyses were performed; it means those details are not reported in the registry record.
The outcome population is identified as ITT. In general, an intention-to-treat population aims to retain participants in the group to which they were assigned, but this study is recorded as non-randomized and single-group. The registry does not explain how ITT was defined for this setting, how participants with missing endpoint data were handled, or whether any additional analysis populations were used.
For the time-to-event endpoint, the record does not describe censoring rules, handling of missed assessments, or procedures for incomplete follow-up. It also does not specify how the clinical benefit outcome was defined or how missing data for the secondary outcomes were treated. These details are needed to understand the analysis population and the sensitivity of the estimates to incomplete observations.
11. 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 |
|---|---|---|---|
| Erlotinib 150 mg/Day | 566 | 1805 | 31.4% |
Other (non-serious) adverse events
Participants with at least one non-serious event at or above the registry's 0% reporting threshold.
| Arm | Participants affected of at risk |
|---|---|
| Erlotinib 150 mg/Day | 1695 of 1797 |
Most frequent serious adverse event terms
| Event term | Organ system | Erlotinib 150 mg/Day |
|---|---|---|
| Dyspnea | Respiratory, thoracic and mediastinal disorders | 188 of 1805 |
| Infection NOS | Infections and infestations | 67 of 1805 |
| Infection - lung (pneumonia) | Infections and infestations | 44 of 1805 |
| Diarrhea | Gastrointestinal disorders | 28 of 1805 |
| Thrombosis/embolism | Vascular disorders | 25 of 1805 |
| Pain NOS | General disorders | 22 of 1805 |
| Bronchopulmonary hemorrhage | Respiratory, thoracic and mediastinal disorders | 21 of 1805 |
| Asthenia | General disorders | 17 of 1805 |
| Fever | General disorders | 17 of 1805 |
| Hemorrhage | Blood and lymphatic system disorders | 17 of 1805 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Erlotinib 150 mg/Day |
|---|---|---|
| Rash | Skin and subcutaneous tissue disorders | 897 of 1797 |
| Dyspnea | Respiratory, thoracic and mediastinal disorders | 691 of 1797 |
| Asthenia | General disorders | 650 of 1797 |
| Diarrhea | Gastrointestinal disorders | 631 of 1797 |
| Anorexia | Metabolism and nutrition disorders | 462 of 1797 |
| Cough | Respiratory, thoracic and mediastinal disorders | 436 of 1797 |
| Dermatology/skin-other | Skin and subcutaneous tissue disorders | 307 of 1797 |
| Pain nos | General disorders | 229 of 1797 |
| Pain - chest wall | Musculoskeletal and connective tissue disorders | 211 of 1797 |
| Fever | General disorders | 210 of 1797 |
Serious events with the highest arm-level rate: dyspnea (10.4%), infection nos (3.7%), infection - lung (pneumonia) (2.4%), diarrhea (1.6%), thrombosis/embolism (1.4%).
The adverse-event record lists 1805 participants at risk for serious adverse events and 566 with serious adverse events. For other adverse events, it lists 1797 participants at risk and 1695 affected. These are the recorded counts; the registry record does not provide further detail in the information available about event ascertainment, follow-up duration for these summaries, or how participants with missing safety information were handled.
The listed serious-event terms and percentages are dyspnea, 10.4%; infection NOS, 3.7%; infection - lung (pneumonia), 2.4%; diarrhea, 1.6%; thrombosis/embolism, 1.4%; and pain NOS, 1.2%. These are reported serious-event terms, not a complete description of every possible adverse event. The registry does not report a death count in this safety entry.
In general, safety counts describe events recorded in a study population; they do not by themselves establish causation. This study has no randomized control group, so these entries do not support a like-for-like comparison with another treatment. The record does not report the specific attribution rules for deciding whether an event was related to treatment.
12. What the Result Does, and Does Not, Mean
The record establishes that a completed phase 2, open-label, non-randomized, single-group study evaluated erlotinib monotherapy in advanced non-small cell lung cancer. It specifies time to disease progression or death as the primary outcome, defines the event and time origin, names the median and 95% confidence interval as summary measures, and describes analysis across six treatment-line cohorts. It also records selected safety counts and serious-event terms.
Those details do not supply the primary outcome results. Cohort-specific medians, confidence intervals, and numerical results for the listed secondary outcomes are not reported in the registry record. The study description therefore cannot establish the observed time to progression or death, its precision, or the size of any treatment effect. The absence of numerical efficacy estimates should not be mistaken for a finding of no effect; it means the record does not report the estimates needed to assess the outcome.
The design also limits what comparisons can mean. Without randomization or a control group, outcomes in the study cannot be contrasted as a randomized estimate of erlotinib relative to another treatment. The treatment-line cohorts are descriptive categories, not equivalent comparator arms. Any differences across them would need cautious interpretation because the record does not establish that the cohorts were comparable.
The safety figures convey the recorded burden of serious and other adverse events in the study, but they do not show whether those events were caused by treatment or how the same population would have fared under a comparator. The record does not report the attribution procedures or a safety comparison group.
Overall, the registry record is informative about the study question, endpoint definition, design, and selected safety reporting. It is not sufficient on its own to quantify the primary outcome or support a comparative benefit-risk conclusion.
13. Why This Trial Matters Statistically
This trial is statistically notable for the way its question and design must be kept distinct. The primary endpoint is a time-to-event measure, and the registry describes both its event definition and its intended summaries. That structure helps readers understand what was to be measured, even though the actual median estimates and confidence intervals are not reported in the record.
The study also illustrates the distinction between stratifying a description and creating a valid comparison. Results were organized into six treatment-line cohorts, including maintenance settings. Such categories can be useful for describing clinical context, but they do not substitute for random allocation. Without a randomized control group, comparisons across cohorts can reflect differences in prior treatment and patient course as well as any treatment-related differences.
Another important statistical point is that a defined outcome is not the same as a reported result. A registry may state the endpoint, population, time frame, and summary measure without reporting the numerical estimates needed to judge magnitude and precision. Here, the primary and secondary outcome values are not reported in the record described, so readers should not infer them from the study title or design.
Finally, the safety entries require the same attention to context. Counts and selected percentages describe events recorded among participants, but a single-group study cannot provide a randomized comparison of safety. The appropriate statistical reading is therefore descriptive: the registry specifies what was measured and some recorded event counts, while leaving important efficacy estimates, analysis details, and comparative evidence unreported.
14. 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 main limitation for interpreting efficacy is that the registry record does not report the primary endpoint estimates. Although it defines time to progression or death and specifies medians with 95% confidence intervals, the cohort-specific numerical values are not reported. Numerical results for the listed secondary outcomes are also not reported. The observed magnitude and precision of the outcomes therefore cannot be assessed from this record.
The single-group, non-randomized design has no like-for-like randomized control comparison. Outcomes observed in the cohort cannot be separated from the course that might have occurred under another treatment or no study treatment. The six treatment-line cohorts are not randomized arms, and the record does not describe adjustments that would address differences among them.
The outcome description gives the assessment schedule but does not report progression criteria, event adjudication, censoring rules, or handling of missed assessments and incomplete follow-up. These omissions matter to interpretation of a time-to-event endpoint. The registry also does not report the specific statistical model, the definition of clinical benefit, or a multiplicity plan for outcomes and treatment-line cohorts.
Safety information is limited to recorded counts and selected serious-event terms. The record does not provide the death count, event attribution procedures, or enough detail about ascertainment and follow-up to support comparative safety conclusions. The anticipated treatment duration of 3-12 months in the study summary should not be interpreted as observed exposure.
Finally, the registry record does not report a protocol-based sample-size justification. The planning illustration is not the trial design and does not represent observed power. These reporting gaps mean that the design and measurement approach can be described, but the available record does not support a full assessment of efficacy, precision, or comparative safety.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: A Study of Tarceva (Erlotinib) Monotherapy in Patients With Advanced Non-Small Cell Lung Cancer (NSCLC) — NCT01996332.
- Registry record last updated 2014-07-10; status last verified 2014-06.
- Results first posted 2014-07-10.
- 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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18. Record Summary
This completed phase 2 study evaluated oral erlotinib (Tarceva) monotherapy in advanced non-small cell lung cancer. It was open-label, non-randomized, and single-group, with enrollment of 1805. The primary endpoint was time from inclusion to disease progression or death, analyzed in the ITT population across six treatment-line cohorts. The registry specifies a median and 95% confidence interval, but the cohort estimates are not reported in the registry record.
Clinical benefit and overall survival by line of treatment were listed as secondary outcomes; their numerical results are not reported. Safety entries list serious and other adverse-event counts and selected serious-event terms. With no randomized comparator and important outcome and analysis details absent, the record supports a description of the study design and reported safety entries, not a controlled estimate of treatment effect.