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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.

Purpose Previous report from the ASCEND-8 trial showed consistent efficacy with less gastrointestinal (GI) toxicity in patients with anaplastic lymphoma kinase-rearranged (ALK+) advanced/metastatic non–small cell lung cancer (NSCLC) treated with ceritinib 450- mg with food compared with 750-mg fasted. In this subgroup analysis, we report outcomes in Asian patients of the ASCEND-8 trial. Materials and Methods Key efficacy endpoints were blinded independent review committee (BIRC)–assessed overall response rate (ORR) and duration of response (DOR) evaluated per Response Evaluation Criteria in Solid Tumors v1.1. Other efficacy endpoints were investigator-assessed ORR and DOR; BIRC- and investigator-assessed progression-free survival (PFS) and disease control rate; overall survival (OS). Safety was evaluated by frequency and severity of adverse events. Results At final data cutoff (6 March 2020), 198 treatment-naïve patients were included in efficacy analysis, of which 74 (37%) comprised the Asian subset; 450-mg fed (n=29), 600-mg fed (n=19), and 750-mg fasted (n=26). Baseline characteristics were mostly comparable across study arms. At baseline, more patients in 450-mg fed arm (44.8%) had brain metastases than in 750-mg fasted arm (26.9%). Per BIRC, patients in the 450-mg fed arm had a numerically higher ORR, 24-month DOR rate and 24-month PFS rate than the 750-mg fasted arm. The 36-month OS rate was 93.1% in 450-mg fed arm and 70.9% in 750-mg fasted arm. Any-grade GI toxicity occurred in 82.8% and 96.2% of patients in the 450-mg fed and 750-mg fasted arms, respectively. Conclusion Asian patients with ALK+ advanced/metastatic NSCLC treated with ceritinib 450-mg fed showed numerically higher efficacy and lower GI toxicity than 750-mg fasted patients. [ABSTRACT FROM AUTHOR]