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.

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.