TEMPORARY REMOVAL: Updated overall survival and final progression-free survival data for patients with treatment-naïve advanced ALK-positive non-small-cell lung cancer in the ALEX study.

Abstract Background The ALEX study demonstrated significantly improved progression-free survival (PFS) with alectinib versus crizotinib in treatment-naive ALK-positive non-small-cell lung cancer (NSCLC) at the primary data cut-off (9 February 2017). We report mature PFS (cut-off: 30 November 2018) and overall survival (OS) data up to 5 years (cut-off: 29 November 2019). Patients and Methods Patients with stage III/IV ALK-positive NSCLC were randomized to receive twice-daily alectinib 600 mg (n = 152) or crizotinib 250 mg (n = 151) until disease progression, toxicity, withdrawal or death. Primary endpoint: investigator-assessed PFS. Secondary endpoints included objective response rate, OS and safety. Results Mature PFS data showed significantly prolonged investigator-assessed PFS with alectinib (hazard ratio [HR] 0.43, 95% confidence interval [CI] 0.32–0.58; median PFS 34.8 versus 10.9 months crizotinib). Median duration of OS follow-up: 48.2 months alectinib, 23.3 months crizotinib. OS data remain immature (37% of events). Median OS was not reached with alectinib versus 57.4 months with crizotinib (stratified HR 0.67, 95% CI 0.46–0.98). The 5-year OS rate was 62.5% (95% CI 54.3–70.8) with alectinib and 45.5% (95% CI 33.6–57.4) with crizotinib, with 34.9% and 9.3% of patients still on study treatment, respectively. The OS benefit of alectinib was seen in patients with central nervous system metastases at baseline (HR 0.58 [95% CI 0.34–1.00]) and those without (HR 0.76 [95% CI 0.45–1.26]). Median treatment duration was longer with alectinib (28.1 versus 10.8 months), and no new safety signals were observed. Conclusions Mature PFS data from ALEX confirmed significant improvement in PFS for alectinib over crizotinib in ALK-positive NSCLC. OS data remain immature, with a higher 5-year OS rate with alectinib versus crizotinib. This is the first global randomized study to show clinically meaningful improvement in OS for a next-generation tyrosine kinase inhibitor versus crizotinib in treatment-naive ALK-positive NSCLC.