P3.02a-015 Ceritinib as First-Line Therapy in Patients with ALK-Rearranged Non-Small Cell Lung Cancer: ASCEND-1 Subgroup Analysis: Topic: ALK Clinical

Abstract

In the open-label, phase 1 ASCEND-1 study (NCT01283516), ceritinib demonstrated durable whole body and intracranial responses in patients with ALK-rearranged (ALK+) non-small cell lung cancer (NSCLC) (Kim et al. Lancet Oncol 2016). Median progression-free survival (PFS) was promising in ALK inhibitor (ALKi)-naïve patients (18.4 months), most of whom had received one or more lines of chemotherapy. Here, efficacy and safety of ceritinib are summarized in a subset of treatment-naïve patients enrolled in ASCEND-1. Patients with ALK+ NSCLC enrolled worldwide received ceritinib 750 mg/day (fasted). Efficacy and safety were evaluated in a subset of patients who had not received any prior systemic antineoplastic therapy. Data cut-off was 16 November 2015. Overall, 246 patients with ALK+ NSCLC (83 ALKi-naïve and 163 ALKi-pretreated) received ≥1 dose of ceritinib, of whom 16 had not received any prior systemic antineoplastic therapy. Among the 16 treatment-naïve patients, three (18.8%) had baseline brain metastases, five (31.3%) an ECOG performance status of 0, and all had stage IV disease. Median time from primary site diagnosis to ceritinib initiation (range) was 1.8 months (1.0–35.9). At data cut-off, median duration of exposure (range) was 18.5 months (0.9–35.7) and median duration of follow-up (range) was 29.6 months (4.7–39.1). In these 16 treatment-naïve patients, per investigator assessment, the overall response rate was 68.8% (95% confidence interval [CI]: 41.3, 89.0) and the disease control rate was 87.5% (95% CI: 61.7, 98.4). Median duration of response was 21.1 months (95% CI: 5.5, 31.1). Median investigator-assessed PFS was 19.3 months (95% CI: 4.2, 26.3), and median overall survival was 39.1 months (95% CI: 19.1, 39.1). Among three patients with baseline brain metastases, one had brain metastases selected as target lesion and achieved a partial intracranial response. The most frequently reported any-grade adverse events (AEs), regardless of study drug relationship, were diarrhea (93.8%), nausea (81.3%), ALT or AST increase (each 81.3%), and vomiting (62.5%). AEs requiring intervention were predominantly managed with dose reduction/interruption. Overall, 13 patients (81.3%) discontinued treatment, due to disease progression (n=6), consent withdrawal (n=3), AEs (n=2), administrative problems or death (each n=1). Ceritinib demonstrated durable efficacy in treatment-naïve patients with ALK+ NSCLC. Safety was consistent with the overall ASCEND-1 study population. An ongoing, prospective, phase 3 study (ASCEND-4) in which patients are randomized to receive either ceritinib or chemotherapy will provide further evidence for the clinical benefit of ceritinib in previously untreated patients with ALK+ NSCLC.