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 Erlotinib With or Without Hydroxychloroquine in Chemo-Naive Advanced NSCLC and (EGFR) Mutations (NCT00977470), a randomized phase 2 study. The primary outcome is Median Progression Free Survival.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT00977470 |
| Phase | Phase 2 |
| Condition | Non-small Cell Lung Cancer |
| Allocation | Randomized |
| Design model | Parallel |
| Masking | None (open label) |
| Enrollment | 76 |
| Arms in the primary outcome | 2 |
| Lead sponsor | Massachusetts General Hospital |
| Results posted | Yes |
2. Clinical Question
Population
Patients with previously untreated advanced non-small cell lung cancer (NSCLC) and EGFR mutations. The registry record lists 76 participants enrolled, with 38 participants in each treatment arm.
Intervention
Erlotinib 150 mg oral daily together with hydroxychloroquine (HCQ) 1000 mg oral daily. The study rationale describes HCQ as a possible way to delay or prevent resistance to tyrosine kinase inhibitor treatment, based on laboratory research.
Comparator
Erlotinib 150 mg oral daily without HCQ. The trial was randomized, open label, and used a parallel-group design, so participants were assigned to one of the two treatment groups.
Primary question
How does median progression-free survival compare between the two treatment groups? Progression-free survival was measured from the start of treatment until reported disease progression. The posted medians are 10.8 months in both groups. The registry record does not report a hazard ratio or another formal estimate of the between-group treatment effect for this endpoint.
The clinical question concerns the addition of HCQ to erlotinib, rather than a comparison of erlotinib with no treatment. Both groups received erlotinib, and the difference in assigned treatment was whether HCQ was included. The proposed rationale was to explore whether adding HCQ could affect the development of resistance; the trial’s posted primary outcome, however, is progression-free survival rather than a direct measurement of resistance. The registry also lists tumor response, overall survival, and treatment-related toxicity among secondary outcomes. Their numerical results are not included in the record, so the primary result alone cannot answer every question about tumor response, survival, or safety.
3. Trial Design
This was a phase 2, randomized, open-label, parallel-group study sponsored by Massachusetts General Hospital. The official title describes previously untreated patients with advanced NSCLC and EGFR mutations. The registry lists enrollment of 76 participants, divided evenly between the two arms, with 38 participants in each. One group received erlotinib 150 mg oral daily; the other received the same erlotinib regimen plus HCQ 1000 mg oral daily.
The record lists the study start as 2009-10 and primary completion as 2015-05. Its status is active, not recruiting. Those registry dates and status describe the study record; they do not establish when every participant began treatment, how long each person was followed, or whether all outcome follow-up was complete. The primary outcome timeframe is described as starting at treatment initiation and continuing until disease progression, assessed up to 10 years.
Random allocation is intended, in general, to make treatment groups comparable at the point of assignment, on average, by distributing both known and unknown prognostic factors. It does not guarantee that every characteristic will be balanced in a trial of this size. The registry record does not report the randomization sequence method, concealment procedure, stratification factors, or details of the allocation process.
Masking is listed as none, so the study was open label. Participants and study staff were not described as blinded to treatment assignment. Open-label status can matter for outcomes that involve judgment, treatment decisions, symptom reporting, or assessment procedures. The progression definition includes imaging findings, but the registry record does not state whether scans were read by blinded reviewers or according to a central review process. The protocol details, analysis population, and planned statistical methods beyond the design labels 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 | Erlotinib | Erlotinib and Hydroxychloroquine |
|---|---|---|
| STARTED | 38 | 38 |
| COMPLETED | 0 | 0 |
| NOT COMPLETED | 38 | 38 |
Reasons for not completing this period:
| Reason | Erlotinib | Erlotinib and Hydroxychloroquine |
|---|---|---|
| Lack of Efficacy | 32 | 30 |
| Physician Decision | 2 | 0 |
| Adverse Event | 1 | 2 |
| Protocol Violation | 1 | 0 |
| Withdrawal by Subject | 0 | 2 |
| Death | 0 | 2 |
| clinical decline | 0 | 1 |
| prolonged recovery post-surgery | 0 | 1 |
| Still on-study | 2 | 0 |
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 | Erlotinib | Erlotinib and Hydroxychloroquine | Total |
|---|---|---|---|---|
| Participants analysed | 38 | 38 | 76 | |
| Age, Continuous | years | 63 (43 to 84) | 65 (37 to 82) | 64 (37 to 84) |
| Sex: Female, Male: Female | Participants | 24 | 23 | 47 |
| Sex: Female, Male: Male | Participants | 14 | 15 | 29 |
| Smoking History: Never smoked | Participants | 28 | 20 | 48 |
| Smoking History: <= 10 pack years | Participants | 4 | 8 | 12 |
| Smoking History: > 10 pack years/current | Participants | 6 | 10 | 16 |
| Histology: Adenocarcinoma | Participants | 33 | 31 | 64 |
| Histology: Non-small cell lung cancer, Not Otherwise Specifie | Participants | 5 | 7 | 12 |
| Brain metastases | Participants | 11 | 16 | 27 |
| Prior chemotherapy | Participants | 9 | 13 | 22 |
6. Primary Endpoint
The registry lists the primary outcome as Median Progression Free Survival, measured over From start of treatment until report of disease progression, assessed up to 10 years..
| Element | Registry entry |
|---|---|
| Result type | Median |
| Measure of spread | Full Range |
| Unit | months |
| Endpoint classification | Time-to-Event Analysis |
The primary endpoint is median progression-free survival, measured in months. The record defines the time period as starting with treatment and ending when disease progression is reported, with assessment planned up to 10 years. Progression is defined as at least a 20% increase in the sum of the longest diameters of target lesions seen on CT scan, or the appearance of one or more new lesions on CT scan.
A time-to-event endpoint incorporates both whether an event occurs and how long it takes to occur. The median is the point in the observed time distribution at which half of the relevant event-time distribution lies on either side, subject to the study’s analysis and censoring methods. It is often useful when event times are skewed or when a typical event-free duration is more informative than an arithmetic average. General statistical interpretation of a median depends on how incomplete follow-up and participants without a recorded event are handled.
The posted median is 10.8 months for erlotinib and 10.8 months for erlotinib plus HCQ. The accompanying reported ranges are 9.0 to 13.6 months and 7.0 to 14.6 months, respectively. The registry record does not report the analysis procedure used to estimate these medians, the number of progression events, or a formal comparative effect estimate. The endpoint is intended to capture time without documented progression; it is not itself a direct measure of tumor response, overall survival, quality of life, or the biological process of treatment resistance.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The central posted result is that median progression-free survival was 10.8 months in each arm. The reported ranges are 9.0 to 13.6 months for erlotinib and 7.0 to 14.6 months for erlotinib plus HCQ. These results describe the registry’s arm-level summaries. They do not, by themselves, establish whether the underlying time-to-progression distributions were alike or different. A median reduces a distribution to one point, and two groups can have identical medians while differing at other parts of their distributions.
The reported ranges convey spread in the values identified by the registry, but they are not a substitute for a comparative effect estimate or its uncertainty. The record labels the dispersion as a full range. It does not report a confidence interval for the difference between groups, a hazard ratio, a p-value, or another formal comparison for the primary endpoint. Thus the precision of the difference between treatment groups cannot be assessed from the medians alone. The record’s analysis note indicates that a two-arm comparison for this median time endpoint was not available or estimable.
Each group included 38 participants. This gives context for the amount of trial information represented by the arm summaries, but sample size alone does not show how many participants experienced progression or remained under observation. The registry record does not give event counts, censoring counts, or follow-up distributions. Without those details, readers cannot determine how much of each estimated median rests on observed progression events versus incomplete observation.
Random assignment supports a comparative trial design, but the existence of randomization does not replace the need for an effect estimate and uncertainty measure. Nor does matching medians demonstrate equivalence or noninferiority: the record does not identify such a design or report a margin for either purpose. The posted data support a descriptive statement about the two medians, not a conclusion that one regimen is better, worse, or equivalent.
The registry lists objective tumor response, overall survival, and treatment-related toxicity as secondary outcomes, but their numerical outcome results are not reported in the record. The primary result should therefore be read narrowly. It concerns the posted median progression-free survival summaries for these study groups, not a complete account of all outcomes or the full evidence base for either treatment.
9. Statistical Methods Explained
Interpreting a randomized trial requires separating the design, the endpoint, and the statistical comparison. In this study, random allocation placed participants in one of two parallel treatment groups. In general, randomization aims to reduce systematic differences between groups at assignment. It does not ensure that groups will be identical, particularly when the number of participants is limited, and it does not by itself provide an estimate of treatment effect. The registry record does not report the randomization method or whether allocation was concealed before assignment.
What does a median time-to-event result describe?
A time-to-event outcome records the time from a defined starting point until a specified event. Here, the stated starting point is treatment initiation and the event is disease progression as defined by imaging. A median is a summary of the event-time distribution. Unlike a mean, it does not require averaging all event times, and it can be useful when the distribution is asymmetric. The median alone does not describe the entire distribution: different distributions can share the same median, and distributions with different medians can still overlap substantially.
In many time-to-event studies, some participants have not experienced the event by the end of their available follow-up. Their event time is not treated as if it were known; methods such as survival analysis account for that incomplete observation through censoring. This is a general explanation, not a claim about the specific analysis used in this trial. The registry record does not report how censoring was defined or handled, the estimator used for the median, the number of participants censored, or the number of progression events.
Why is an effect estimate important?
A comparison between groups ordinarily needs a measure that expresses the relative or absolute treatment contrast, together with information about its uncertainty. For time-to-event outcomes, a hazard ratio is one possible comparative measure; other approaches may compare survival probabilities at a selected time or compare restricted time summaries. These methods answer different statistical questions and rely on different assumptions. The registry record does not report a hazard ratio or another formal comparative estimate for the primary endpoint. The posted medians of 10.8 months in both groups are descriptive summaries and cannot supply that missing comparison on their own.
A confidence interval, in general, communicates uncertainty around an estimated quantity under the analysis model. It is not a range that contains a known treatment effect with certainty, and it should be interpreted in relation to the estimate and the method used to construct it. The values 9.0 to 13.6 months and 7.0 to 14.6 months are reported as full ranges in the registry record. They should not be relabeled as confidence intervals. No confidence interval for a treatment contrast is reported for this endpoint.
How should the ranges and equal medians be read?
The range communicates the span identified in the record, while the median locates the middle of the reported time distribution. Neither tells readers how observations are distributed inside the range. Equal reported medians do not show that all participants had the same experience, that the overall distributions were identical, or that the treatments were equivalent. They also do not establish that an effect is absent. A formal comparison would need an estimate and uncertainty measure, or another prespecified inferential approach, neither of which is reported for this outcome.
The trial was unmasked. As a general matter, lack of masking can affect behavior, additional care, symptom reporting, or assessment, depending on the outcome and trial procedures. Progression is defined using CT findings in this record, but the record does not explain who reviewed images, whether review was blinded, or whether scans were assessed centrally. Those details would help readers judge the potential for assessment-related bias but are not reported in the registry record.
What do the planning assumptions mean?
Sample-size calculations based on an observed effect are planning illustrations, not observed trial outcomes and not evidence that a study had a particular probability of detecting an effect. Such illustrations depend on assumptions about the target effect, significance level, allocation, and statistical approximation. The stated planning framework specifies a two-sided significance level of 0.05, equal allocation, and a normal approximation, with the target effect expressed as a fraction of the observed effect. For time-to-event outcomes, the planning description refers to a total event count. These assumptions describe the planning illustration, not necessarily the design calculations used when the trial was planned. The registry record does not report the trial’s own sample-size justification or the effect size and event assumptions used in its original design.
General statistical power is a design property under stated assumptions, not a measure of whether the observed result is true. A retrospective calculation based on the effect observed in a trial should not be interpreted as observed power or as a replacement for an effect estimate and confidence interval. The registry record does not report an original power calculation or a prespecified target effect. Consequently, the planned ability of this study to detect a clinically meaningful difference cannot be assessed from the registry information.
Finally, the record labels the study phase, allocation, masking, and model, but those broad design descriptors do not establish every analytic choice. The analysis population, treatment of protocol deviations, missing-data approach, statistical model, and sensitivity analyses are not reported in the registry record. Those omissions limit reproduction of the primary analysis and interpretation of how robust the reported medians may be to alternative assumptions.
10. Multiplicity, Missing Data and Analysis Populations
The registry record lists 8 outcome measures and identifies 3 secondary outcomes: treatment-related toxicity, objective tumor response, and overall survival. It also lists 1 analysis. These counts do not explain which outcomes were tested together, which analyses were prespecified, or how the investigators handled multiple statistical comparisons. An adjustment for multiplicity, an outcome hierarchy, and any distinction between confirmatory and exploratory analyses are not reported in the registry record.
Multiplicity matters in general when several hypotheses are examined. The more comparisons made, the greater the chance that at least one result may appear unusual by chance if each is interpreted without regard to the others. Methods such as adjustment, prioritization, or clearly labeling analyses as exploratory can address different aspects of this issue. The record does not say whether any such approach was planned or used, so no claim about multiplicity control can be made.
Missing-data and analysis-population details are also not reported. The record does not specify whether the primary analysis included everyone as randomized, only participants who received treatment, or another defined group. It does not describe withdrawals, missing assessments, protocol deviations, or how incomplete follow-up was handled. These details are especially relevant for a time-to-event outcome, because the timing and reason for loss of observation can affect interpretation.
The primary outcome timeframe extends from treatment start until reported progression, assessed up to 10 years. This describes the stated assessment window, not the observed follow-up achieved by each participant. The registry record does not report median follow-up, numbers at risk over time, or the amount of missing outcome information. It also does not report interim analyses or stopping rules. Without these details, readers cannot assess the influence of incomplete observation, interim monitoring, or analytical choices on the reported result.
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 | 4 | 38 | 10.5% |
| Erlotinib and Hydroxychloroquine | 2 | 38 | 5.3% |
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 | 38 of 38 |
| Erlotinib and Hydroxychloroquine | 38 of 38 |
Most frequent serious adverse event terms
| Event term | Organ system | Erlotinib | Erlotinib and Hydroxychloroquine |
|---|---|---|---|
| Pulmonary embolism | Vascular disorders | 1 of 38 | 0 of 38 |
| Dehydration | Metabolism and nutrition disorders | 1 of 38 | 0 of 38 |
| Pneumothorax | Respiratory, thoracic and mediastinal disorders | 0 of 38 | 1 of 38 |
| Infection, nos | Infections and infestations | 0 of 38 | 1 of 38 |
| Constitutional disorders - other | General disorders | 1 of 38 | 0 of 38 |
| Skin - pain | Skin and subcutaneous tissue disorders | 1 of 38 | 0 of 38 |
| Pneumonia | Infections and infestations | 1 of 38 | 0 of 38 |
| Respiratory - other | Respiratory, thoracic and mediastinal disorders | 1 of 38 | 0 of 38 |
| Death NOS | General disorders | 0 of 38 | 1 of 38 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Erlotinib | Erlotinib and Hydroxychloroquine |
|---|---|---|---|
| Diarrhea w/o prior colostomy | Gastrointestinal disorders | 33 of 38 | 32 of 38 |
| Fatigue | General disorders | 25 of 38 | 27 of 38 |
| Nausea | Gastrointestinal disorders | 18 of 38 | 23 of 38 |
| Rash: acne/acneiform | Skin and subcutaneous tissue disorders | 18 of 38 | 21 of 38 |
| Cough | Respiratory, thoracic and mediastinal disorders | 23 of 38 | 16 of 38 |
| Rash/desquamation | Skin and subcutaneous tissue disorders | 20 of 38 | 13 of 38 |
| Skin-other | Skin and subcutaneous tissue disorders | 20 of 38 | 8 of 38 |
| Anorexia | Metabolism and nutrition disorders | 13 of 38 | 15 of 38 |
| Dyspnea | Respiratory, thoracic and mediastinal disorders | 16 of 38 | 12 of 38 |
| Dry skin | Skin and subcutaneous tissue disorders | 12 of 38 | 12 of 38 |
Serious events with the highest arm-level rate: pulmonary embolism (2.6%), dehydration (2.6%), pneumothorax (2.6%), infection, nos (2.6%), constitutional disorders - other (2.6%).
The registry lists serious adverse events among 4 of 38 participants in the erlotinib group and 2 of 38 participants in the erlotinib-plus-HCQ group. These are participant counts within each group. They describe the registry’s serious-event reporting and are not, by themselves, a comparison adjusted for follow-up duration, exposure, or other factors. The record does not provide a statistical comparison of serious adverse events between groups.
The listed serious-event terms each have a reported frequency of 2.6%: pulmonary embolism, dehydration, pneumothorax, infection, not otherwise specified, constitutional disorders, other, and skin pain. A term appearing in this list does not establish that every participant with a serious event experienced that term, nor does the list provide a complete account of event timing, recurrence, severity grades, or relationship to study treatment. The registry record does not report the number of deaths.
For other adverse events, the record lists 38 affected participants out of 38 at risk in each arm. The description of these events and the detailed grading or event-level counts are not reported. Serious and other adverse-event summaries should be read as separate registry groupings. They do not alone establish comparative safety, and the available counts do not support a conclusion about the likelihood of an event for an individual patient.
12. What the Result Does, and Does Not, Mean
The registry results describe a randomized phase 2 comparison of erlotinib alone with erlotinib plus HCQ in previously untreated advanced NSCLC with EGFR mutations. For the primary endpoint, the posted median progression-free survival is 10.8 months in each arm. The reported ranges differ: 9.0 to 13.6 months for erlotinib and 7.0 to 14.6 months for the combination. These are arm-level summaries, not a formal estimate of how much adding HCQ changed progression-free survival.
Because the registry does not report a hazard ratio, confidence interval for a treatment contrast, or p-value for this endpoint, the precision of the comparative effect is not established in the posted record. Identical medians cannot establish equivalence, noninferiority, or absence of an effect. They also cannot show that treatment groups had identical event-time distributions. A non-significant result, if one were reported, would not by itself demonstrate equivalence; in this record, a formal test result is not reported at all.
The biological rationale in the study description is that laboratory research suggested HCQ might help delay or prevent resistance to a tyrosine kinase inhibitor. The primary endpoint is progression-free survival, which measures time until documented progression; it is not a direct assay of resistance. The posted median result therefore does not establish whether the proposed biological mechanism occurred. Nor does it establish an effect on overall survival, objective response, or quality of life. Although the registry lists some secondary outcomes, their numerical results are not reported in the record.
The safety counts describe reported serious adverse events among participants in each arm, with 4 of 38 and 2 of 38 participants affected, respectively. Without additional information about event details, follow-up, exposure, and comparative analysis, these counts do not support a definitive safety comparison. They should be understood as descriptive registry results.
Overall, the result is informative as a record of the two reported medians and the listed adverse-event counts. It leaves important comparative and precision questions unresolved. It is not a recommendation about treatment, and it cannot establish what an individual patient should receive.
13. Why This Trial Matters Statistically
This trial is statistically notable because it asks a focused add-on question: whether including HCQ alongside erlotinib changes progression-free survival compared with erlotinib alone. Both groups received the same stated erlotinib regimen, making the assigned addition of HCQ the principal treatment contrast described in the registry. A randomized parallel-group design is an appropriate framework for studying such a contrast, because random assignment can reduce systematic confounding at the start of treatment.
The posted result also illustrates why a single summary statistic is not enough for a full comparison. Both groups have a median progression-free survival of 10.8 months, yet the reported ranges are not identical. Medians and ranges provide useful descriptive information, but they do not reveal the shape of the time-to-event distributions or quantify uncertainty in the treatment difference. A comparative estimate and its precision are needed to judge how compatible the results are with effects of different sizes.
The question has further statistical importance because the rationale concerns treatment resistance, while the primary endpoint is progression-free survival. These concepts are related in the trial rationale but are not interchangeable measurements. The endpoint records a clinical event-time outcome; it does not directly measure the mechanism proposed in the study description. Keeping the biological hypothesis distinct from the statistical endpoint helps avoid overstating what the reported outcome can establish.
Finally, the record provides a useful reminder that registry results may include arm-level outcome summaries without a complete inferential analysis. Missing comparative estimates, analysis details, and secondary outcome results limit what can be concluded. These limitations are part of the statistical interpretation, not evidence that the intervention did or did not have an effect.
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 principal limitation for interpreting the primary result is the absence of a reported comparative effect estimate and its uncertainty. The registry gives a median of 10.8 months in each arm and reports ranges, but a formal two-arm comparison for this median time endpoint is identified as unavailable or not estimable. Readers therefore cannot quantify the magnitude or precision of a treatment contrast from the posted primary summaries.
The record does not provide the number of progression events, censoring details, numbers at risk, or observed follow-up distribution. Although assessment is described as extending up to 10 years, the actual follow-up for participants is not reported. These omissions make it difficult to assess how much information underlies the medians and how incomplete observation may affect interpretation.
Important design and analysis details are not reported in the registry record, including the randomization procedure, allocation concealment, analysis population, handling of missing data, statistical model, and sensitivity analyses. The open-label design is listed, but the record does not say whether imaging review was blinded or centralized. These details can matter when assessing the risk of bias and whether results are robust to different analytical decisions.
The registry lists secondary outcomes, but their numerical results are not reported in the information. It also does not report multiplicity procedures, interim analyses, or the trial’s sample-size justification. Consequently, the available record is not enough to reconstruct the full statistical analysis plan or determine how secondary findings were interpreted. The enrollment of 76 and equal arm sizes provide context, but do not independently establish adequacy of sample size or precision.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Erlotinib With or Without Hydroxychloroquine in Chemo-Naive Advanced NSCLC and (EGFR) Mutations — NCT00977470.
- Registry record last updated 2025-10-15; status last verified 2025-09.
- Results first posted 2017-06-06.
- 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
The registry record describes a randomized, open-label, parallel-group phase 2 study sponsored by Massachusetts General Hospital. It enrolled 76 participants with previously untreated advanced NSCLC and EGFR mutations, with 38 assigned to erlotinib 150 mg oral daily and 38 to erlotinib 150 mg oral daily plus HCQ 1000 mg oral daily. The study start is listed as 2009-10, primary completion as 2015-05, and status as active, not recruiting.
The primary endpoint was median progression-free survival. The reported median was 10.8 months in each arm, with ranges of 9.0 to 13.6 months for erlotinib and 7.0 to 14.6 months for the combination. A formal comparative estimate for this endpoint is not reported. Serious adverse events were reported for 4 of 38 participants in the erlotinib arm and 2 of 38 in the combination arm. The registry also lists secondary outcomes, but their numerical results and key analysis details are not reported in the record.