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

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 ALK-rearranged 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. 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. 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). Treatment with crizotinib was associated with trend toward increased risk of development of BM. Only KPS was associated with survival.