Front-line treatment of ceritinib improves efficacy over crizotinib for Asian patients with anaplastic lymphoma kinase fusion NSCLC: The role of systemic progression control.

Abstract

BackgroundApproximately 3%–5% of lung adenocarcinoma is driven by anaplastic lymphoma kinase (ALK) fusion oncogene, whose activity can be suppressed by multiple ALK inhibitors. Crizotinib and ceritinib have demonstrated superior efficacy to platinum‐based chemotherapy as front‐line treatment for patients with ALK‐positive advanced non‐small cell lung cancer (NSCLC). However, the direct comparison between them in the front‐line setting remains lacking.MethodsA total of 48 patients with ALK‐positive, previously untreated advanced NSCLC, who received crizotinib and ceritinib as front‐line treatment were retrospectively investigated. The efficacy and pattern of disease progression were analyzed.ResultsPatients receiving ceritinib treatment were significantly younger than those receiving crizotinib treatment (52.0 vs. 63.0, P = 0.016). The median progression‐free survival (PFS) was significantly longer with ceritinib than with crizotinib treatment (32.3 vs. 12.9 months; log‐rank P = 0.020); the hazard ratio for disease progression or death, 0.27 (95% CI, 0.08–0.90; P = 0.033). An objective response was noted in all patients in the ceritinib group and in 23 patients in the crizotinib group (74.2%; 95% CI, 59.0 to 88.5). The rate of systemic progression was significantly lower over time with ceritinib treatment compared to crizotinib treatment (cause‐specific hazard ratio, 0.21; 95% CI 0.06–0.73; P = 0.014). Serious adverse events were noted in one (2.9%) patient showing elevated liver function in the crizotinib group and three (23.1%) patients showing diarrhea in the ceritinib group. Dose reduction was needed in five out of 13 (38.5%) patients receiving ceritinib treatment.ConclusionCeritinib showed higher efficacy associated with a better control of systemic progression compared to crizotinib for the front‐line treatment of ALK‐positive advanced NSCLCs.