First-line ceritinib versus chemotherapy in patients (pts) with advanced ALK rearranged (ALK+) non-small cell lung cancer (NSCLC): ASCEND-4 Asian subgroup analysis

Abstract

Background: In global phase III ASCEND‐4 study (NCT01283516), ceritinib 750 mg/ day (fasted), demonstrated statistically significant and clinically meaningful improvement in PFS by BIRC (median, 16.6 mos [95% CI: 12.6, 27.2] vs 8.1 mos [95% CI: 5.8, 11.1]; HR=0.55; p<0.001) compared to chemotherapy (pemetrexed 500 mg/m2+ cisplatin 75 mg/m2 or carboplatin AUC 5‐6, followed by pemetrexed maintenance) in untreated pts with advanced ALK+ NSCLC. Here, we report the efficacy and safety of ceritinib in Asian pts from ASCEND‐4 study. Methods: Pts with stage IIIB/IV, ALK+(centrally tested IHC), nonsquamous NSCLC, ≥1 measurable lesion per RECIST v1.1, andWHOPS 0‐2 were eligible. Efficacy and safety were evaluated in Asian pts who had not received prior systemic anticancer therapy except neo‐/adjuvant therapy. Data cutoff: June 24, 2016. Results: Among 376 pts randomized (1:1) in the study, 158 pts were Asian, with 76 in ceritinib arm and 82 in chemotherapy arm. Of these, 25 pts (32.9%) in ceritinib arm and 21 (25.6%) in chemotherapy arm had brain metastases at baseline. Median duration of treatment exposure: 64.5 wks (ceritinib, N=76) and 35.0 wks (chemotherapy, N=75). Median duration from randomization to data cutoff: 18.3 mos. Ceritinib demonstrated superior PFS by BIRC (median, 26.3 mos; 95% CI: 8.6, NE; HR=0.66) compared to chemotherapy (Table). Most common (≥50%; all grades; all‐causality) AEs in ceritinib arm: diarrhea (85.5%), ALT increased (73.7%), vomiting (73.7%), AST increased (69.7%), and nausea (69.7%). Incidence of grade 3/4 AEs was <6%, except ALT increased (38.2%), GGT increased (22.4%), AST increased (21.1%), fatigue (7.9%), amylase increased (6.6%), and hyperglycemia (6.6%). Only 7 pts (9.2%) discontinued ceritinib due to AEs. Conclusions: In Asian pts with ALK+NSCLC, ceritinib demonstrated durable and clinically meaningful efficacy and a safety profile consistent with overall ASCEND‐4 study results.