Brain metastases and mortality in patients with ALK + metastatic non-small cell lung cancer treated with second-generation ALK tyrosine kinase inhibitors as first-line targeted therapies: An observational cohort study

Background

Brain metastases (BM) are common in patients with ALK + metastatic non-small cell lung cancer (mNSCLC). Limited contemporary real-world evidence exists on the burden of BM in these patients. This study estimated the cumulative incidence of BM in patients with ALK + mNSCLC treated with second-generation ALK tyrosine kinase inhibitors (TKI) as first-line (1L) targeted therapies and assessed the association between BM and mortality.

Materials and Methods

Using a 100 % sample of Medicare fee-for-service and Advantage beneficiaries from 2017 to 2022, patients > 65 years with ALK + mNSCLC (index date = 1L alectinib/brigatinib following lung cancer diagnosis) were identified. The cumulative incidence of BM was calculated, accounting for competing risk of death, overall and by age and race/ethnicity. To assess the association between BM and death, a time-varying Cox proportional hazards model compared the risk of death in those with incident, and baseline BM, separately, to those without BM, adjusting for confounders.

Results

In 1040 patients, 289 (28 %) had baseline BM. In 751 patients without baseline BM, the cumulative incidence of BM was 20 % after 5 years. After 4 years, the cumulative incidence of BM was highest in patients ≥ 85 years (25 %) and in non-White patients (23 %). Patients with incident BM had 2.6 times the risk of mortality compared to patients without BM (hazard ratio (HR): 2.59, 95 % confidence interval (CI): 1.98–3.38), while patients with baseline BM had 1.5 times the risk of mortality compared to patients without BM (HR: 1.46, 95 % CI: 1.20–1.77).

Conclusions

Patients with ALK + mNSCLC treated with second-generation ALK TKIs as 1L targeted therapies faced a high burden of BM. Incident BM were associated with increased mortality risk to a greater extent than baseline BM. Efforts are needed to provide safe and efficacious approaches to prevention and treatment of BM, including additional monitoring as required, in patients with ALK + mNSCLC.