Alectinib versus crizotinib in previously untreated ALK-positive advanced non-small cell lung cancer: final overall survival analysis of the phase III ALEX study.

BACKGROUND

ALEX, a global, randomized, phase III trial evaluated alectinib versus crizotinib in patients with advanced ALK-positive non-small cell lung cancer (NSCLC). This final analysis provides mature overall survival (OS), duration of response (DOR) and long-term safety data.

PATIENTS AND

METHODS

Treatment-naïve patients with stage III/IV ALK-positive NSCLC were randomly assigned to receive alectinib [600 mg twice daily (b.i.d.)] or crizotinib (250 mg b.i.d.) until disease progression, unacceptable toxicity, withdrawal, or death. Primary endpoint was investigator-assessed progression-free survival (previously reported). Key secondary endpoints included OS, DOR and safety.

RESULTS

A total of 303 patients (alectinib, n = 152; crizotinib, n = 151) were enrolled. At the updated data cut-off (28 April 2025), after a median follow-up of 53.5 (alectinib) and 23.3 (crizotinib) months, median OS was 81.1 [95% confidence interval (CI) 62.3 months-not estimable] versus 54.2 (95% CI 34.6-75.6 months) months, respectively [hazard ratio (HR) 0.78; 95% CI 0.56-1.08]. Improvement in median OS was observed with alectinib in patients with and without central nervous system (CNS) metastases at baseline [with CNS metastases: 63.4 (n = 59) versus 30.9 (n = 53) months with alectinib versus crizotinib, respectively (HR 0.68; 95% CI 0.40-1.15); without CNS metastases: 94.0 (n = 93) versus 69.8 (n = 98) months (HR 0.87; 95% CI 0.58-1.32)]. Median DOR in confirmed responders was longer with alectinib (42.3 months, 95% CI 31.3-51.3 months) versus crizotinib [11.1 months, 95% CI 7.9-13.0 months (HR 0.41; 95% CI 0.30-0.56)]. Long-term safety (median duration of alectinib treatment, 28.1 months) remained consistent with earlier reports, with no new or unexpected safety concerns identified.

CONCLUSIONS

These final OS data show the sustained long-term systemic and intracranial efficacy of alectinib in the first-line treatment of ALK-positive NSCLC and confirm alectinib as a standard of care in this setting.