Efficacy of different sequential patterns after crizotinib progression in advanced anaplastic lymphoma kinase‐positive non–small cell lung cancer

BACKGROUND: The efficacy difference between the second‐ and third‐generation of anaplastic lymphoma kinase‐tyrosine kinase inhibitors (ALK‐TKIs) after crizotinib failure in advanced ALK‐positive non–small cell lung cancer (NSCLC) has not been clarified. This study evaluates the efficacy of different sequential patterns after crizotinib progression. METHODS: Data of patients who met the study criteria were retrospectively analyzed. The Kaplan–Meier method was used to draw survival curves, log‐rank method was used to compare the differences between groups, and Cox multivariate analysis was used to evaluate the significance of influencing factors. RESULTS: A total of 128 patients developed disease progression after crizotinib. The overall survival (OS) of 57 patients in the sequential second‐generation ALK‐TKIs group was significantly longer than that of 65 patients with other systemic treatment (58.5 months vs. 33.0 months, p < 0.001); The OS of the direct sequential lorlatinib group was significantly longer than the second‐generation ALK‐TKIs group (114.0 months vs. 58.5 months, p = 0.020). Similarly, of the 48 patients who developed disease progression after first‐ and second‐generation ALK‐TKIs treatment, 16 patients with sequential lorlatinib had significantly longer OS than the others (62.0 months vs. 43.0 months, p = 0.014). The progression‐free survival (PFS) of second‐line and third‐ or later‐line lorlatinib were statistically different (20.0 months vs. 5.5 months, p = 0.011). CONCLUSIONS: The application of next‐generation ALK‐TKIs after crizotinib progression significantly prolonged survival, whereas direct sequencing lorlatinib seemed advantageous. Similarly, lorlatinib also prolonged survival in patients with first‐ and second‐generation ALK‐TKIs failure.