Randomized, Phase 3 Study of First-Line Ceritinib vs Chemotherapy in Patients with ALK-Positive NSCLC (ASCEND-4)
ASCEND-4 enrolled 376 adult patients with untreated ALK+, advanced, nonsquamous non–small-cell lung cancer (NSCLC). Patients were randomized to ceritinib (750 mg QD) (n = 189, including 59 with brain metastases [BM]) or chemotherapy (n = 187 [62 with BM]). Chemotherapy included pemetrexed 500 mg/m2 and cisplatin 75 mg/m2 or carboplatin AUC 5 to 6 for 4 cycles followed by maintenance pemetrexed. Crossover from chemotherapy to ceritinib was allowed at progression; 43% of patients did so.
After median follow-up of 19.7 months, the study met its primary objective: ceritinib demonstrated a statistically significant improvement in progression-free survival (PFS) compared with chemotherapy. Median PFS was 16.6 months (95% confidence interval [CI], 12.6-27.2 months) and 8.1 months (95% CI, 5.8-11.1 months), respectively. The hazard ratio for PFS was 0.55 (P <0.001). Although overall survival (OS) data were immature at interim analysis, estimated 24-month OS rates favored ceritinib over chemotherapy: 71% versus 58%, respectively.
Objective response rate (ORR) based on independent review favored ceritinib (73% vs 27%), as did median duration of response compared with chemotherapy (24 vs 11 months). Among patients with measurable BM at baseline and 1 or more postbaseline assessments, intracranial ORR based on independent assessment was higher with ceritinib versus chemotherapy (73% vs 27%).
The most common adverse events (AEs) occurring in more than 50% of patients taking ceritinib were diarrhea (85%), nausea (69%), vomiting (66%), ALT increase (60%), and AST increase (53%). Overall, 5% of ceritinib- and 11% of chemotherapy-treated patients discontinued due to AEs that were believed to be drug-related.
Researchers concluded that first-line ceritinib achieved a clinically meaningful improvement in median PFS compared with chemotherapy. Ceritinib also achieved durable tumor responses. A high proportion of intracranial responses were noted in patients with measurable BM. The safety of ceritinib was consistent with previous reports.
De Castro G, et al. WCLC 2016. Abstract PL 03.07. ID 4987.