CMET-08. PROGNOSTIC FACTORS AND OUTCOMES OF PATIENTS WITH CENTRAL NERVOUS SYSTEM (CNS) METASTATIC ALK-REARRANGED NON-SMALL CELL LUNG CANCER (NSCLC)

Abstract

PURPOSE: ALK-rearrangement is present in 5% of NSCLC patients. Crizotinib has significantly prolonged progression-free survival (PFS); however, about 70% of patients who progress on crizotinib develop CNS metastases. Prognostic factors for development of CNS metastases in ALKrearranged NSCLC are unknown. The purpose is to evaluate the impact of patient characteristics and treatment-specific factors on the risk of development of brain metastases (BM) in patients with ALK-rearranged NSCLC. METHODS: This was an IRB-approved, single-center, retrospective study of patients with stage IIIB or IV ALK-rearranged NSCLC diagnosed between 1/2009 and 2/2017 at Memorial Sloan Kettering Cancer Center. Patient characteristics and treatment were collected. OS and intracranial PFS were calculated using Kaplan-Meier methodology. Cox proportional hazards modeling was used to associate variables with BM, OS, and PFS and to estimate hazard ratios (HR) and 95% confidence intervals (CI). Treatments were modeled in a time-dependent fashion. RESULTS: Ninety-eight patients were identified; 44 (45%) were male, 70 (71%) were Caucasian, and 73 (74%) had Karnofsky performance status (KPS) >70. Twenty (20%) had BM at time of diagnosis and 34 (34%) developed BM at median of 7.5 months (range 0.07 - 62.7) from initial diagnosis. Sixteen (16%) received crizotinib prior to BM diagnosis with trend toward increased risk for development of BM (HR: 2.4, 95%CI:1.0-6.3; p=0.06). Too few patients received ceritinib or alectinib prior to BM diagnosis to model (n=3 and n=0, respectively). Age, sex, and tyrosine kinase inhibitors (TKI) dose reductions were not associated with development of BM. Thirty-eight patients received crizotinib on or after date of BM diagnosis with non-significant increase in risk of death (HR:3.8, 95%CI:0.9-16.1; p=0.07). Only higher KPS score (> 70) was associated with improved OS (HR: 0.15, 95%CI:0.03-0.67; p=0.01). CONCLUSION: Treatment with crizotinib was associated with trend toward increased risk of development of BM. Only KPS was associated with survival.