Evaluation of Ceritinib-Treated Patients (Pts) with Anaplastic Lymphoma Kinase Rearranged (Alk+) Non-Small Cell Lung Cancer (Nsclc) and Brain Metastases in the Ascend-1 Study

Abstract

Aim: Brain metastases, seen in ∼30–50% of NSCLC pts, are associated with poor prognosis. ALK+ NSCLC is sensitive to the ALK inhibitor (ALKi) crizotinib, but resistance invariably occurs, often with progression in new or existing brain metastases. Ceritinib (LDK378), a novel ALKi, is highly active in pts with ALK+ NSCLC and has demonstrated central nervous system activity. Here we report efficacy and safety of ceritinib therapy in the subset of ALK+ NSCLC pts with brain metastases treated in the phase I ASCEND-1 study. Methods: Safety and efficacy of ceritinib 750 mg/day was analyzed based on investigator assessment of adult pts with advanced ALK+ NSCLC and with clinically and neurologically stable brain metastases at study entry. Results: Of 246 ALK+ NSCLC pts at 750 mg/day, 124 had brain metastases at study entry; 98 had ALKi pretreatment and 26 were ALKi treatment naïve. Pts with brain metastases had a median age of 51.0 years; 85.5% had an ECOG performance status of ≤1. Most pts were either Caucasian (58.1%) or Asian (39.5%); median time from initial NSCLC diagnosis to first ceritinib dose was 20.5 months. Median duration of exposure to ceritinib was 27 weeks. Efficacy is shown below. Endpointa ALKi-pretreated patients with brain metastases ALKi-naïve patients with brain metastases All NSCLC patients with brain metastases n = 98 n = 26 n = 124 ORR, n (%)[95% CI] 49 (50.0)[39.7, 60.3] 18 (69.2)[48.2, 85.7] 67 (54.0)[44.9, 63.0] DOR, median (months) [95% CI] 6.9[4.8, 8.5] NEb[5.5, NE] 7.0[5.5, 9.7] PFS, median (months) [95% CI] 6.7[4.9, 8.5] 8.3[4.6, NE] 6.9[5.4, 8.4] NE = Not estimable aOverall antitumor activity, bDOR rate at 6 months 65.9% [95% CI: 35.4, 84.5]