Alectinib versus crizotinib as first-line treatment in patients with advanced ALK-mutated non-small cell lung cancer: a Chinese, real-world cohort study

<bold>Background:</bold> The clinical trial confirmed that alectinib is more effective than crizotinib as a first-line treatment in ALK-mutated NSCLC. The purpose of this study was to investigate the real-world effectiveness of both drugs in a real-world setting. <bold>Methods:</bold> Patients diagnosed with NSCLC and harboring ALK rearrangement confirmed by IHC, FISH, or NGS were included. The primary endpoint of this study was progression-free survival (PFS), with secondary endpoints including overall survival (OS), objective response rate (ORR), disease control rate (DCR), and safety. <bold>Results:</bold> A total of 261 treatment-naive patients were evaluated, with 128 receiving crizotinib and 133 receiving alectinib. Alectinib demonstrated significant longer PFS compared to crizotinib (45.5 vs 16.6 months, p<0.001). However, there was negligible difference between the two drugs in terms of OS (not reached vs 74.5 months, p = 0.14). Both alectinib and crizotinib have shown excellent performance in terms of ORR and DCR, with no significant differences between them. PFS2 was defined as the time from the first day of second-line treatment to PD. No significant difference was observed between different second-line ALK-TKIs in PFS2 in both groups. The incidence of adverse drug reactions was higher in the crizotinib group (50%) compared to the alectinib group (34.6%) (p = 0.01). The predominant adverse reactions in the crizotinib group were elevated ALT or AST and gastrointestinal reactions, while in the alectinib group adverse reactions primarily manifested as elevated ALT or AST and increased bilirubin. The occurrence rates of grade 3 or higher adverse reactions were comparable (5.5% vs 4.5%). <bold>Conclusion:</bold> Alectinib is the preferred drug for ALK mutation patients when compared to crizotinib