Research Article|Articles in Press, 100483

Real-world Comparative Effectiveness of First-Line Alectinib Versus Crizotinib in Patients with Advanced ALK-Positive NSCLC with or without Baseline Central Nervous System Metastases

Open AccessPublished:February 23, 2023DOI:
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      Alectinib demonstrated superior efficacy to crizotinib in the phase 3 ALEX study and is a preferred initial treatment for patients with advanced ALK-positive NSCLC. To understand the efficacy of alectinib in US clinical practice, we conducted a retrospective real-world comparative effectiveness analysis of first-line alectinib versus crizotinib.


      Adults with advanced ALK-positive NSCLC who received first-line alectinib (from December 11, 2015) or crizotinib (from January 01, 2014) were included from a real-world database. Propensity scores were applied to balance baseline characteristics. Real-world data (RWD), including progression-free survival (rwPFS), overall survival (rwOS), time to new CNS metastases (rwTTNCM), and outcomes in patients with/without baseline CNS metastases were analysed. The ALEX-like RWD cohort (filtered by ALEX laboratory eligibility criteria) was used to compare real-world comparative effectiveness with ALEX.


      The RWD cohort comprised 364 patients (141 alectinib; 223 crizotinib); rwPFS (weighted hazard ratio [wHR] = 0.46; 95% CI: 0.33–0.65) and rwOS (wHR = 0.46; 95% CI: 0.31–0.69) were significantly improved with alectinib versus crizotinib. In patients with baseline brain scans, a significant rwPFS benefit was seen regardless of baseline CNS metastases. rwTTNCM was delayed with alectinib versus crizotinib in patients with (wHR = 0.28, 95% CI: 0.16–0.52) and without (wHR = 0.42, 95% CI: 0.24–0.76) baseline CNS metastases. The ALEX-like RWD cohort comprised 325 patients (120 alectinib; 205 crizotinib); alectinib showed similar rwPFS benefits with ALEX.


      Outcomes were significantly improved with first-line alectinib versus crizotinib in patients with advanced ALK-positive NSCLC in the US real-world setting.