Real-world incidence, prevalence, and clinical impact of brain metastases in patients with ALK-positive metastatic non–small cell lung cancer treated with first-line ALK tyrosine kinase inhibitors
Bibliographic record
Abstract
INTRODUCTION: This real-world study evaluated the incidence and clinical impact of brain metastases in patients with anaplastic lymphoma kinase-positive (ALK + ) metastatic non-small cell lung cancer (mNSCLC) receiving first-line (1L) treatment with second- or first-generation ALK tyrosine kinase inhibitors (TKIs). METHODS: A retrospective analysis of patients with ALK + mNSCLC receiving 1L ALK TKI was conducted using Flatiron data. Baseline and incident brain metastases were assessed, and their impact on mortality was quantified using time-varying Cox proportional hazards models. RESULTS: Among 475 patients, 80 % received second-generation (n = 382) and 20 % received first-generation (n = 93) ALK TKIs. Baseline brain metastases were present among 32 % patients in second-generation cohort and 29 % in first-generation cohort. Among patients without baseline brain metastases, 5-year cumulative incidence of brain metastases during the follow-up period was 21 % in second-generation cohort and 25 % in first-generation cohort. In the second-generation cohort, patients who developed incident brain metastasis had a statistically significant 3-fold-higher risk of death (hazard ratio [HR], 2.97 [95 % confidence interval [CI], 1.59-5.53]) compared to those who did not develop incident brain metastases. In the first-generation cohort, the risk of death was numerically higher for patients with incident brain metastasis compared to those without (HR, 1.42 [0.58-3.51]), although this was not statistically significant, likely limited by the small sample size. Baseline brain metastases, compared with no baseline brain metastases, were not associated with a significantly increased risk of death, after adjusting for incident brain metastasis and other covariates. CONCLUSIONS: Brain metastases remains a clinically important concern in patients with ALK + mNSCLC treated with 1L ALK TKIs. Incident brain metastases were strongly associated with increased mortality, highlighting the need for CNS-penetrant 1L therapies with durable intracranial efficacy.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.002 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.001 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.002 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".