PURPOSE/OBJECTIVE(S): Brain metastases are reported in 15%-35% of patients with anaplastic lymphoma kinase-positive (ALK+) nonesmall cell lung cancer (NSCLC). Crizotinib has proven efficacy against ALK+ tumors, but its outcomes in recipients with co-occurring brain metastases have not been widely assessed in real-world settings, particularly in Europe (EU). The objective of this analysis was to therefore assess clinical outcomes in an EU population of ALK+ NSCLC patients with brain metastases treated with crizotinib in routine practice.
MATERIALS/METHODS: A retrospective medical record review was conducted in selected EU countries for adults (18 years) with ALK+ NSCLC treated with crizotinib as first- or later-line therapy for metastatic disease between October 1, 2012 and July 1, 2015. Patients with brain metastases prior crizotinib initiation were selected for sub-analysis. Patients receiving crizotinib in an interventional trial were excluded. Applicable IRB approvals were obtained. Physicians and research staff at participating sites abstracted the study data. Patient data were de-identified, anonymized, and pooled across countries. Descriptive analyses were conducted to assess clinician-documented systemic overall response rate (ORR) and intracranial response (ICR), as well as 1-year overall survival (estimated via Kaplan-Meier).
RESULTS: Data were extracted from 303 patients in 5 EU countries, which included a pooled total of 23 patients with brain metastases. Mean (SD) age at diagnosis for these 23 patients was 59.6 (12.6) years and most were male (74%) and had ECOG 0 or 1 (87%). Adenocarcinoma was the most common histology (87%). Approximately half (52%) received whole brain radiation therapy (nZ9) or stereotactic radiosurgery (nZ3) prior to crizotinib initiation. Of the 23 patients studied, 7 received crizotinib as firstline therapy for metastatic disease and 16 received it in second/later line. Sixteen patients were deceased at record abstraction. In first-line crizotinib users, systemic ORR was 57.1% and 1-year survival was 71.4%. Additional results are presented in the table.
CONCLUSION: Systemic ORR in ALK+ NSCLC patients with brain metastases may be more favorable in first-line crizotinib users. ORR (43.8%) and ICR (31.2%) for later-line crizotinib users were consistent with a recent study of later-line crizotinib users with brain metastases pooled from the PROFILE 1005 and 1007 trials reporting a 46%-53% ORR and 18%-33% ICR. Although the ICR observed here cannot be attributed to crizotinib due to possible confounding from pre-crizotinib cranial radiation therapy, our findings indicate that outcomes in crizotinib-treated ALK+ NSCLC patients with brain metastases in clinical studies may translate to regular practice.
