\zaAlectinib versus crizotinib in previously untreated ALK-positive advanced non-small cell lung cancer: Final overall survival analysis of the Phase III ALEX study

Abstract

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 [BID]) or crizotinib (250 mg BID) 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 cutoff (28 April 2025), after a median follow-up of 53.5 (alectinib) and 23.3 (crizotinib) months, median OS was 81.1 (95% CI 62.3-not estimable) versus 54.2 (95% CI 34.6-75.6) 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 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) versus crizotinib (11.1 months, 95% CI 7.9-13.0 [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.

Keywords: ALEX; alectinib; anaplastic lymphoma kinase; non-small cell lung cancer; overall survival.