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.