Ceritinib Efficacy and Safety in Treatment-Naive Asian Patients With Advanced ALK-Rearranged NSCLC: An ASCEND-4 Subgroup Analysis

Introduction: In the phase 3 ASCEND-4 study, ceritinib exhibited improved progression-free survival (PFS) by Blinded Independent Review Committee (BIRC) assessment versus the standard first-line chemotherapy in patients with advanced ALK-rearranged NSCLC. Here, we assessed the efficacy and safety of ceritinib in the subgroup of Asian patients from the ASCEND-4 trial. Methods: Treatment-naive patients with stage IIIB or IV ALK-rearranged nonsquamous NSCLC were randomized in a one-to-one ratio to receive either oral ceritinib 750 mg/day (fasted) daily or intravenous chemotherapy ([cisplatin 75 mg/m² or carboplatin area under the curve 5–6 plus pemetrexed 500 mg/m²] every three wk, followed by pemetrexed maintenance). The primary end point was PFS by BIRC assessment. Results: Of 376 randomized patients, 158 (42.0%) were Asian (ceritinib arm: N = 76; chemotherapy arm: N = 82). The median time from randomization to the cutoff date (June 24, 2016) was 18.3 months (range = 13.5–34.2) in the Asian subgroup. The median PFS (by BIRC assessment) was 26.3 months (95% confidence interval [CI]: 8.6–not estimable) and 10.6 months (95% CI: 6.7–15.0), with an estimated 34% risk reduction in PFS (hazard ratio = 0.66, 95% CI: 0.41–1.05) in the ceritinib arm versus chemotherapy arm. The most common adverse events of any grade were diarrhea (85.5%), increased alanine aminotransferase and vomiting (73.7% each), and increased aspartate aminotransferase and nausea (69.7% each) in the ceritinib arm, and nausea (49.3%), vomiting (42.7%), and anemia (40.0%) in the chemotherapy arm. Conclusion: Ceritinib was effective and safe in treatment-naive Asian patients with advanced ALK-rearranged NSCLC. The findings were largely consistent with that of the overall study population.